World Trade Center Health Program; Petition 023-Uterine Cancer, Including Endometrial Cancer; Finding of Insufficient Evidence, 49954-49959 [2019-20364]
Download as PDF
49954
Federal Register / Vol. 84, No. 185 / Tuesday, September 24, 2019 / Rules and Regulations
Authority: 33 U.S.C. 1321(d); 42 U.S.C.
9601–9657; E.O. 13626, 77 FR 56749, 3 CFR,
2013 Comp., p. 306; E.O. 12777, 56 FR 54757,
3 CFR, 1991 Comp., p. 351; E.O. 12580, 52
FR 2923, 3 CFR, 1987 Comp., p. 193.
PART 300—NATIONAL OIL AND
HAZARDOUS SUBSTANCES
POLLUTION CONTINGENCY PLAN
1. The authority citation for part 300
continues to read as follows:
■
2. Table 1 of appendix B to part 300
is amended by revising the entry for
‘‘FL’’, ‘‘Escambia Wood—Pensacola’’,
‘‘Pensacola’’ to read as follows:
■
Appendix B to Part 300—National
Priorities List
TABLE 1—GENERAL SUPERFUND SECTION
State
Site name
City/county
*
*
FL ..............................................................
*
*
Escambia Wood—Pensacola ...................
*
*
Pensacola .................................................
*
*
*
*
*
*
Notes a
*
P.
*
a
= Based on issuance of health advisory by Agency for Toxic Substances and Disease Registry (if scored, HRS score need not be greater
than or equal to 28.50).
*
*
*
*
*
*
*
P = Sites with partial deletion(s).
*
*
*
*
*
[FR Doc. 2019–20347 Filed 9–23–19; 8:45 am]
BILLING CODE 6560–50–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
42 CFR Part 88
[NIOSH Docket 094]
World Trade Center Health Program;
Petition 023—Uterine Cancer,
Including Endometrial Cancer; Finding
of Insufficient Evidence
Centers for Disease Control and
Prevention, HHS.
ACTION: Denial of petition for addition of
a health condition.
AGENCY:
On April 23, 2019, the
Administrator of the World Trade
Center (WTC) Health Program received
a petition (Petition 023) to add
‘‘endometrial cancer’’ to the List of
WTC-Related Health Conditions (List).
Upon reviewing the scientific and
medical literature, including
information provided by the petitioner,
the Administrator has determined that
the available evidence does not have the
potential to provide a basis for a
decision on whether to add the major
site uterine cancer, including its
subtype, endometrial cancer, to the List.
The Administrator also finds that
insufficient evidence exists to request a
recommendation of the WTC Health
Program Scientific/Technical Advisory
Committee (STAC), to publish a
proposed rule, or to publish a
determination not to publish a proposed
rule.
DATES: The Administrator of the WTC
Health Program is denying this petition
khammond on DSKJM1Z7X2PROD with RULES
SUMMARY:
VerDate Sep<11>2014
15:47 Sep 23, 2019
Jkt 247001
for the addition of a health condition as
of September 24, 2019.
ADDRESSES: Visit the WTC Health
Program website at https://
www.cdc.gov/wtc/received.html to
review Petition 023.
FOR FURTHER INFORMATION CONTACT:
Rachel Weiss, Program Analyst, 1090
Tusculum Avenue, MS: C–48,
Cincinnati, OH 45226; telephone (855)
818–1629 (this is a toll-free number);
email NIOSHregs@cdc.gov.
SUPPLEMENTARY INFORMATION:
Table of Contents
A. WTC Health Program Statutory Authority
B. Procedures for Evaluating a Petition for
Cancer
C. Petition 023
D. Assessment of Scientific and Medical
Information
E. Administrator’s Final Decision on Whether
To Propose the Addition of Uterine
Cancer, Including Endometrial Cancer, to
the List
F. Approval To Submit Document to the
Office of the Federal Register
A. WTC Health Program Statutory
Authority
Title I of the James Zadroga 9/11
Health and Compensation Act of 2010
(Pub. L. 111–347, as amended by Pub.
L. 114–113), added Title XXXIII to the
Public Health Service (PHS) Act,1
establishing the WTC Health Program
within the Department of Health and
Human Services (HHS). The WTC
Health Program provides medical
monitoring and treatment benefits for
health conditions on the List to eligible
firefighters and related personnel, law
1 Title
XXXIII of the PHS Act is codified at 42
U.S.C. 300mm to 300mm-61. Those portions of the
James Zadroga 9/11 Health and Compensation Act
of 2010 found in Titles II and III of Public Law 111–
347 do not pertain to the WTC Health Program and
are codified elsewhere.
PO 00000
Frm 00014
Fmt 4700
Sfmt 4700
enforcement officers, and rescue,
recovery, and cleanup workers who
responded to the September 11, 2001,
terrorist attacks in New York City, at the
Pentagon, and in Shanksville,
Pennsylvania (responders), and to
eligible persons who were present in the
dust or dust cloud on September 11,
2001, or who worked, resided, or
attended school, childcare, or adult
daycare in the New York City disaster
area (survivors).
All references to the Administrator of
the WTC Health Program
(Administrator) in this document mean
the Director of the National Institute for
Occupational Safety and Health
(NIOSH) or his designee.
Pursuant to section 3312(a)(6)(B) of
the PHS Act, interested parties may
petition the Administrator to add a
health condition to the List in 42 CFR
88.15. Within 90 days after receipt of a
valid petition to add a condition to the
List, the Administrator must take one of
the following four actions described in
section 3312(a)(6)(B) of the PHS Act and
§ 88.16(a)(2) of the Program regulations:
(1) Request a recommendation of the
STAC, (2) publish a proposed rule in the
Federal Register to add such health
condition, (3) publish in the Federal
Register the Administrator’s
determination not to publish such a
proposed rule and the basis for such
determination, or (4) publish in the
Federal Register a determination that
insufficient evidence exists to take
action under (1) through (3) above.
B. Procedures for Evaluating a Petition
for Cancer
In addition to the regulatory
provisions, the WTC Health Program
has developed policies to guide the
E:\FR\FM\24SER1.SGM
24SER1
Federal Register / Vol. 84, No. 185 / Tuesday, September 24, 2019 / Rules and Regulations
khammond on DSKJM1Z7X2PROD with RULES
review of submissions and petitions,2 as
well as the analysis of evidence
supporting the potential addition of a
type of cancer to the List.3
A valid petition must include
sufficient medical basis for the
association between the September 11,
2001, terrorist attacks and the health
condition to be added; in accordance
with WTC Health Program policy,
reference to a peer-reviewed, published,
epidemiologic study about the health
condition among 9/11-exposed
populations or to clinical case reports of
health conditions in WTC responders or
survivors may demonstrate the required
medical basis.4 Studies linking 9/11
agents 5 or hazards to the petitioned
health condition may also provide
sufficient medical basis for a valid
petition.
After the Program has determined that
a petition is valid, the Administrator
must direct the Program to conduct a
systematic literature search (a keyword
search of relevant scientific databases)
to gather information about the
following: (1) Studies about the type of
cancer requested to be added to the List
among 9/11-exposed populations, (2)
studies showing a potential causal
association between the requested
cancer and a health condition on the
List, and (3) classifications of the World
Health Organization’s International
Agency for Research on Cancer (IARC)
and the National Toxicology Program
(NTP) Report on Carcinogens relevant to
the requested cancer. Peer-reviewed,
published, epidemiologic studies of the
cancer in 9/11-exposed populations are
considered relevant. The quantity and
quality of relevant studies are reviewed
for their potential to provide a basis for
2 See WTC Health Program [2014], Policy and
Procedures for Handling Submissions and Petitions
to Add a Health Condition to the List of WTCRelated Health Conditions, May 14, 2014, https://
www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandling
Procedures14May2014.pdf.
3 See WTC Health Program [2019], Policy and
Procedures for Adding Types of Cancer to the List
of WTC-Related Health Conditions, May 1, 2019,
https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_
Addition_of_Cancer_Policy_UPDATED_050719508.pdf.
4 See supra note 2.
5 9/11 agents are chemical, physical, biological, or
other hazards reported in a published, peerreviewed exposure assessment study of responders,
recovery workers, or survivors who were present in
the New York City disaster area, or at the Pentagon
site, or the Shanksville, Pennsylvania site, as those
locations are defined in 42 CFR 88.1, as well as
those hazards not identified in a published, peerreviewed exposure assessment study, but which are
reasonably assumed to have been present at any of
the three sites. See WTC Health Program [2018],
Development of the Inventory of 9/11 Agents, July
17, 2018, https://wwwn.cdc.gov/ResearchGateway/
Content/pdfs/Development_of_the_Inventory_of_911_Agents_20180717.pdf.
VerDate Sep<11>2014
15:47 Sep 23, 2019
Jkt 247001
deciding whether to propose adding the
type of cancer to the List.
If the Program determines that the
relevant studies have the potential to
provide a basis for deciding whether to
propose adding the type of cancer to the
List, the cancer type may be added to
the List if one of the four following
methods is met:
Method 1. Epidemiologic Studies of
September 11, 2001-Exposed Populations.
The peer-reviewed, published,
epidemiologic studies of 9/11-exposed
populations are assessed by applying the
following criteria extrapolated from the
Bradford Hill criteria, as appropriate:
a. Strength of the association between a 9/
11 exposure and a type of cancer (including
the precision of the risk estimate 6),
b. Consistency of the findings across
multiple studies. If only a single published
epidemiologic study is available for
assessment, the consistency of findings
cannot be evaluated and more emphasis will
be placed on evaluating the strength of the
association and the precision of the risk
estimate,
c. Biological gradient, or dose-response
relationships between 9/11 exposures and
the type of cancer, and
d. Plausibility and coherence with known
facts about the biology of the type of cancer.
Method 2. Established Causal Associations.
A type of cancer may be added to the List
if there is well-established scientific support
published in multiple epidemiologic studies
for a causal association between that cancer
and a condition already on the List of WTCRelated Health Conditions.
Method 3. Review of Evaluations of
Carcinogenicity in Humans.
A type of cancer may be added to the List
under Method 3 if both of the following
criteria are satisfied:
3A. Published Exposure Assessment
Information. A 9/11 agent included in the
Inventory of 9/11 Agents 7 is identified, and
3B. Evaluation of Carcinogenicity in
Humans from Scientific Studies. NTP has
determined that the [identified] 9/11 agent is
known to be a human carcinogen or is
reasonably anticipated to be a human
carcinogen, and IARC has determined there
is sufficient or limited evidence that the 9/
11 agent causes [the requested] type of
cancer.
Method 4. Review of Information Provided
by the WTC Health Program Scientific/
Technical Advisory Committee.8
6 A precision of the risk estimate describes the
uncertainty inherent in estimating the strength of
association (the effect size) between exposure and
health effect from observational data. It is expressed
as a confidence interval illustrating a range of
values that contains the true effect size. A narrow
confidence interval indicates a more precise
measure of the effect size and a wider interval
indicates greater uncertainty.
7 The Inventory of 9/11 Agents is composed of
those agents identified in Tables 1–4 of the
document, Development of the Inventory of 9/11
Agents. See supra note 5.
8 The WTC Health Program Scientific/Technical
Advisory Committee may be convened by the
Administrator if he determines that its advice
would be helpful. See supra note 3 at Sec. V.
PO 00000
Frm 00015
Fmt 4700
Sfmt 4700
49955
A type of cancer may be added to the List
if the STAC has provided a reasonable basis
for adding a type of cancer.
If the evaluation of evidence required
for any of the four methods
demonstrates that the criteria in that
method are satisfied, the Administrator
will propose the addition of the type of
cancer to the List.
C. Petition 023
On April 23, 2019, the Administrator
received a petition (Petition 023)
requesting the addition of ‘‘endometrial
cancer’’ to the List.9 The petition
included a 2002 study by Lioy et al.10
and a 2017 study by McElroy et al.11
which together provided sufficient
medical basis for the petition to be
considered valid because they
demonstrate the presence of 9/11 agents,
including cadmium, at the WTC site and
that cadmium exposure is associated
with a statistically significant increase
in endometrial cancer risk. However,
because neither Lioy et al. [2002] nor
McElroy et al. [2017] is a peer-reviewed,
published, epidemiologic study of
endometrial cancer (or the major site,
uterine cancer) in a 9/11-exposed
population, neither study is considered
relevant nor are they further reviewed in
this action.
In the Program’s List of WTC-Related
Health Conditions, types of cancer are
identified by the major cancer site/
histology groups that are commonly
used in the reporting of cancer
incidence data, using the groupings
standardized by the National Cancer
Institute’s Surveillance, Epidemiology
and End Results Program (SEER) for
national cancer surveillance.12 Cancer
subtypes are not included in the List.
Because endometrial cancer is a subtype
of uterine cancer,13 the Program has
9 See Petition 023, WTC Health Program: Petitions
Received, https://www.cdc.gov/wtc/received.html.
10 Lioy PJ, Weisel CP, Millette JR, Eisenreich S,
Vallero D, Offenberg J, Turpin B, Zhong M, Cohen
MD, Prophete C, Yang I, Stiles R, Chee G, Johnson
W, Porcja R, Alimokhtari S, Hale RC, Weschler C,
Chen LC [2002], Characterization of the Dust/
Smoke Aerosol that Settled East of the World Trade
Center (WTC) in Lower Manhattan after the
Collapse of the WTC11 September 2001, Environ
Health Perspect 110(7), 703–714.
11 McElroy JA, Kruse RL, Guthrie J, Gangnon RE,
Robertson JD [2017], Cadmium Exposure and
Endometrial Cancer Risk: A Large Midwestern U.S.
Population-Based Case-Control Study, PLoS ONE
12(7): e0179360.
12 National Cancer Institute [2008], Surveillance
Epidemiology and End Results: Site Recode ICD–O–
3/WHO 2008 Definition, https://seer.cancer.gov/
siterecode/icdo3_dwhoheme//.
13 Endometrial cancer develops in the lining of
the uterus, called the endometrium. Although
endometrial uterine cancer is the most common
type of uterine cancer, accounting for more than 90
percent of cases, there are other types of uterine
E:\FR\FM\24SER1.SGM
Continued
24SER1
49956
Federal Register / Vol. 84, No. 185 / Tuesday, September 24, 2019 / Rules and Regulations
determined that the scope of this
petition and subsequent Program review
should include both endometrial cancer
and the major site, uterine cancer.
D. Assessment of Scientific and Medical
Information
In response to Petition 023, the
Program conducted both a systematic
literature search to identify peerreviewed, published studies of uterine
cancer, including endometrial cancer, in
9/11-exposed women, as well as a
review of NTP and IARC classifications
of 9/11 agents, including those 9/11
agents identified by IARC as
carcinogenic agents with sufficient or
limited evidence that the agent causes
uterine cancer, including endometrial
cancer, in humans.14 The National
Cancer Institute has not identified any
of the health conditions on the List of
WTC-Related Health Conditions as
known risk factors for uterine or
endometrial cancer; therefore, a
systematic literature search for studies
regarding a causal association between
uterine or endometrial cancer and a
health condition on the List was not
conducted.15
khammond on DSKJM1Z7X2PROD with RULES
Literature Search Results
Two publications were identified in
the search for studies specifically
regarding uterine cancer, including
endometrial cancer, among 9/11exposed populations, thus meeting the
Program’s criteria for further evaluation:
Li et al. [2012] 16 and its update Li et al.
[2016].17 In addition to the two Li et al.
publications found in the literature
search, the Program was aware of
additional studies examining all types
cancer. See https://www.cancer.gov/types/uterine/
patient/endometrial-treatment-pdq.
14 Databases searched include: CINAHL, Embase,
NIOSHTIC–2, ProQuest Health & Safety, PsycINFO,
Ovid MEDLINE, Scopus, Toxicology Abstracts/
TOXLINE, and WTC Health Program Bibliographic
Database. Keywords used to conduct the search
include: Endometrial neoplasm, endometrial
cancer, endometrial carcinoma, malignant
neoplasm of endometrium, adenocarcinoma of
endometrium, cancer of the endometrium, Uterine
Neoplasm, malignant neoplasm of corpus uteri,
uterine cancer, uterine carcinoma. The literature
search was conducted in English-language journals
on May 23, 2019.
15 No health conditions on the List of WTCRelated Health Conditions are known risk factors
for uterine cancer. See https://www.cancer.gov/
types/uterine/hp/endometrial-prevention-pdq.
16 Li J, Cone JE, Kahn AR, Brackbill RM, Farfel
MR, Greene CM, Hadler JL, Stayner LT, Stellman
SD [2012], Association between World Trade Center
Exposure and Excess Cancer Risk, JAMA
308(23):2479–88.
17 Li J, Brackbill RM, Liao TS, Qiao B, Cone JE,
Farfel MR, Hadler JL, Kahn AR, Konty KJ, Stayner
LT, Stellman SD [2016], Ten-Year Cancer Incidence
in Rescue/Recovery Workers and Civilians Exposed
to the September 11, 2001 Terrorist Attacks on the
World Trade Center, Am J Ind Med 59(9):709–21.
VerDate Sep<11>2014
15:47 Sep 23, 2019
Jkt 247001
of cancer in 9/11-exposed
subpopulations (rescue and recovery
workers and survivors); these additional
studies were also reviewed to determine
whether they may provide further
insight into cancer incidence and
mortality applicable to the evaluation of
uterine cancer, including endometrial
cancer: Jordan et al. [2011] 18 and its
update Jordan et al. [2018],19 ZeigOwens et al. [2011] 20 and its update
Moir et al. [2016],21 Solan et al.
[2013],22 Kleinman et al. [2015],23 and
Stein et al. [2016].24 Of the additional
studies, only Zeig-Owens et al. [2011]
and its update Moir et al. [2016] were
found not to be relevant (they were not
peer-reviewed, published, studies of
uterine or endometrial cancer in the 9/
11-exposed population) because neither
addressed cancers in female WTC
responders. The other five additional
studies, along with Li et al. [2012] and
Li et al. [2016], were found to be
relevant and were reviewed for quantity
and quality, below.
The Program reviewed the NTP
Report on Carcinogens 25 and found that
18 Jordan HT, Brackbill RM, Cone JE,
Debcoudhury I, Farfel MR, Greene CM, Hadler JL,
Kennedy J, Li J, Liff J, Stayner L, Stellman SD
[2011], Mortality among Survivors of the Sept 11,
2001, World Trade Center Disaster: Results from the
World Trade Center Health Registry Cohort, Lancet
378(9794):879–87.
19 Jordan HT, Stein CR, Li J, Cone JE, Stayner L,
Hadler JL, Brackbill RM, Farfel MR [2018], Mortality
among Rescue and Recovery Workers and
Community Members Exposed to the September 11,
2001 World Trade Center Terrorist Attacks, 2003–
2014, Environ Res 163:270–9.
20 Zeig-Owens R, Webber MP, Hall CB, Schwartz
T, Jaber N, Weakley J, Rohan TE, Cohen HW,
Derman O, Aldrich TK, Kelly K, Prezant DJ [2011],
Early Assessment of Cancer Outcomes in New York
City Firefighters after the 9/11 Attacks: an
Observational Cohort Study, Lancet 378(9794):898–
905.
21 Moir W, Zeig-Owens R, Daniels RD, Hall CB,
Webber MP, Jaber N, Yiin JH, Schwartz T, Liu X,
Vossbrinck M, Kelly K, Prezant D [2016], Post-9/11
Cancer Incidence in World Trade Center-Exposed
New York City Firefighters as Compared to a Pooled
Cohort of Firefighters from San Francisco, Chicago
and Philadelphia (9/11/2001–2009), Am J Ind Med
59(9):722–30.
22 Solan S, Wallenstein S, Shapiro M, Teitelbaum
SL, Stevenson L, Kochman A, Kaplan J,
Dellenbaugh C, Kahn A, Biro FN, Crane M, Crowley
L, Gabrilove J, Gonsalves L, Harrison D, Herbert R,
Luft B, Markowitz SB, Moline J, Niu X, Sacks H,
Shukla G, Udasin I, Lucchini RG, Boffetta P,
Landrigan PJ [2013], Cancer Incidence in World
Trade Center Rescue and Recovery Workers, 2001–
2008, Environ Health Perspect 21(6):699–704.
23 Kleinman EJ, Christos PJ, Gerber LM, Reilly JP,
Moran WF, Einstein AJ, Neugut AI [2015], NYPD
Cancer Incidence Rates 1995–2014 Encompassing
the Entire World Trade Center Cohort, J Occup
Environ Med 57(10):e101–13.
24 Stein CR, Wallenstein S, Shapiro M, Hashim D,
Moline JM, Udasin I, Crane MA, Luft BJ, Lucchini
RG, Holden WL [2016], Mortality among World
Trade Center Rescue and Recovery Workers, 2002–
2011, Am J Ind Med 59(2):87–95.
25 National Toxicology Program, HHS [2016],
Report on Carcinogens, 14th Edition (Research
PO 00000
Frm 00016
Fmt 4700
Sfmt 4700
twelve 9/11 agents 26 are known to be
human carcinogens and twenty-seven 9/
11 agents are reasonably anticipated to
be human carcinogens. 27 However,
IARC has not determined that any of
these thirty-nine 9/11 agents
demonstrate sufficient or limited
evidence of a causal association with
uterine or endometrial cancer in
humans.28
Review of Relevant Studies
The studies identified as relevant
during the literature review process
were further assessed to determine
whether they have sufficient quality and
quantity to demonstrate a potential to
support the addition of uterine cancer,
including endometrial cancer. The
relevant studies introduced above are
described below, including a
description of their respective strengths
and limitations.
Jordan et al. [2011] conducted a
mortality study among the cohort of
WTC Health Registry enrollees that
included 13,337 rescue/recovery
workers (3,188 women) and 28,593
survivors (16,733 women) living in New
York City at the time of their
enrollment. The authors identified
deaths occurring in 2003–2009 through
linkage to New York City vital records
and the National Death Index (NDI).
Standardized mortality ratios (SMRs)
were calculated with New York City
rates from 2000 to 2009 as the reference.
Within the cohort, proportional hazards
were used to examine the relation
between WTC-related exposure levels
(high, intermediate, or low for each
group, based on exposure to the dust
cloud, and time and duration working
on the pile) and all-cause mortality, but
not mortality for specific cancers. AllTriangle Park, NC). https://ntp.niehs.nih.gov/go/
roc14.
26 As identified in the Inventory of 9/11 Agents,
see supra notes 7 and 5.
27 The 39 total 9/11 agents identified by NTP are
as follows: Arsenic, Asbestos, Benzene, Beryllium,
1,3-Butadiene, Cadmium, Nickel, Silica, Solar
Radiation, Soot, Sulfuric Acid, Trichloroethylene
(Known To Be Human Carcinogens); as well as
Acetaldehyde, Acrylonitrile, Benz[a]anthracene,
Benzo[k]fluoranthene, Benzo[a]pyrene, Carbon
Tetrachloride, Chloroform, Cobalt,
Dibenz[a,h]anthracene, 1,4-Dichlorobenzene,
Dichlorodiphenyltrichloroethane, 1,2Dichloroethane, Dichloromethane, 1,3Dichloropropene, Diesel Exhaust Particulates, 1,4Dioxane, Hexachlorobenzene, Lead,
Hexachlorocyclohexane, Mirex, Naphthalene,
Nickel, Polybrominated Biphenyls, Polychlorinated
Biphenyls, Styrene, Tetrachloroethylene, and
Toluene Diisocyanates (Reasonably Anticipated To
Be Human Carcinogens).
28 International Agency for Research on Cancer
[1976], IARC Monographs on the Evaluation of
Carcinogenic Risk of Chemicals to Man: Cadmium,
Nickel, Some Epoxides, Miscellaneous Industrial
Chemicals and General Considerations on Volatile
Anesthetics, Volume 11; Lyon, France.
E:\FR\FM\24SER1.SGM
24SER1
Federal Register / Vol. 84, No. 185 / Tuesday, September 24, 2019 / Rules and Regulations
khammond on DSKJM1Z7X2PROD with RULES
cause SMRs were significantly lower
than that expected for rescue/recovery
workers (SMR = 0.45, 95% CI
(confidence interval) 0.38–0.53) and
survivors (SMR = 0.61, 95% CI 0.56–
0.66). There were no significantly
elevated SMRs for any category of
cancer examined, including cancer of
female genital organs, among all studied
Registry enrollees (SMR = 0.82, 95% CI
0.49–1.28), rescue/recovery workers
(SMR = 0.67, 95% CI 0.08–2·43), or
survivors (SMR = 0.84, 95% CI 0.49–
1.35). Separate SMRs for cancer of
specific types of female genital organs,
including uterine cancer, were not
provided. SMRs were adjusted for age,
sex, race, and calendar year. Adjusted
hazard ratios (AHRs) were adjusted for
age, sex, race and ethnic origin, income,
smoking, and, for survivors, Registry
recruitment source. This study’s
limitations include possible selection
bias, since enrollment in the Registry is
voluntary. Exposure reporting may also
be subject to recall error because 9/11
exposures were self-reported 2 to 3
years after the September 11, 2001
terrorist attacks and subsequent cleanup of the sites. The healthy worker
effect puts the population of rescue/
recovery workers at a lower risk of
cancer compared to the general
population,29 which includes persons
who are chronically ill, hospitalized, or
otherwise unemployable. In addition,
other potential confounders, such as
family cancer history and occupational
exposures prior to September 11, 2001,
were not measured.
Jordan et al. [2018] updated their
2011 study, discussed above, by
including the full cohort of WTC Health
Registry enrollees, not only those living
in New York City at time of enrollment,
and adding 5 years of follow-up. The
2018 update included 29,280 rescue/
recovery workers (6,422 women) and
39,643 survivors (21,126 women). The
authors used New York City population
mortality rates from 2003 to 2012 as the
primary reference, and also conducted a
secondary analysis using U.S.
population comparison rates from 2003
to 2011. Proportional hazards were used
to examine the relation between WTCrelated exposure levels (high,
intermediate, or low for each group,
based on time and duration in lower
Manhattan) and total mortality, as well
as overall cancer mortality, but not
29 The healthy worker effect is a form of selection
bias ‘‘typically seen in observational studies of
occupational exposures with improper choice of
comparison group (usually general population).’’
See Chowdhury R, Shah D, Payal AR, [2017],
Healthy Worker Effect Phenomenon: Revisited with
Emphasis on Statistical Methods—A Review, Indian
J Occup Environ Med 21(1), 2–8.
VerDate Sep<11>2014
15:47 Sep 23, 2019
Jkt 247001
mortality for specific cancer types.
Overall cancer SMRs were not elevated
for rescue/recovery workers (SMR =
0.94, 95% CI 0.84–1.05), but were
significantly elevated among survivors
(SMR = 1.14, 95% CI 1.06–1.24) when
compared to the New York City
population; no elevated SMRs were
reported for all cancers using the
general U.S. population as reference.
Cancers of the female genital organs
were not significantly elevated among
rescue/recovery workers or survivors
(observed deaths = 7, SMR = 0.67, 95%
CI 0.27–1.39 and observed deaths = 43,
SMR = 1.17, 95% CI 0.85–1.58,
respectively). The authors also
examined 119 sub-categories of the
major causes of death, but only reported
statistically significant results; uterine
cancers were not among the reported
causes of death, suggesting that the risk
of uterine cancer was not significantly
elevated. No statistically significant
elevations and no significant trends
were observed in the analyses of the
association between WTC-related
exposures and overall cancer mortality.
Like the previously reviewed study,
Jordan et al. [2018] is prone to selection
bias, because enrollment in the Registry
was voluntary. Further, 9/11 exposures
were self-reported 2 to 3 years after the
September 11, 2001 terrorist attacks,
and thus are subject to recall error. The
healthy worker effect may put the
population of rescue/recovery workers
at a lower risk of cancer compared with
the general population. An analogous
effect has been seen in people who
volunteer for health studies and might
have contributed to the low relative
mortality in both the rescue/recovery
and survivor participants. As in the
previously described study, other
potential confounders, such as family
cancer history and occupational
exposures prior to September 11, 2001,
were not measured.
Li et al. [2012] conducted a cancer
incidence study among enrollees in the
WTC Health Registry who were
residents of New York State on
September 11, 2001, and had no history
of cancer at the time of enrollment. A
total of 55,778 individuals were eligible
for the study, including 21,850 involved
in rescue/recovery (4,185 women) and
33,928 survivors not involved in rescue/
recovery (18,922 women). The authors
identified cancers by linkage to 11 state
cancer registries based on the state of
residence of the cohort member, and
based expected numbers of cancers on
New York State cancer rates. They used
qualitative descriptions of 9/11
exposures to classify Registry enrollee
exposure as high, intermediate, or low
PO 00000
Frm 00017
Fmt 4700
Sfmt 4700
49957
based on time and duration in lower
Manhattan. The authors conducted
separate analyses for rescue/recovery
workers and for survivors, and
presented separate results for the period
of enrollment through 2006 (early
period) and 2007 through 2008 (later
period). Among rescue/recovery
workers, the standardized incidence
ratio (SIR) 30 for all cancer sites
combined was not statistically
significantly elevated in either period
(early period, SIR = 0.94; 95% CI, 0.82–
1.08; later period SIR = 1.14; 95% CI,
0.99–1.30). Uterine cancer incidence
was not elevated for rescue/recovery
workers during the early period (five
cases or less [the precise number of
cases was not reported, likely because of
restrictions on reporting small
numbers], SIR = 0.97, 95% CI 0.2–2.83),
and no cases were reported during the
later period. Among survivors, no
significantly increased incidence for all
cancer sites combined was observed in
either period. Uterine cancer incidence
was not elevated for survivors during
the early or late periods (early: observed
uterine cancers = 16, SIR = 1.01, 95%
CI 0.58–1.65 and late: observed uterine
cancers = 14, SIR = 1.01, 95% CI 0.55–
1.69, respectively). Results of analyses
to assess the risk of uterine cancer as a
function of 9/11 exposure levels were
not reported. SIRs were stratified by age
(5-year age groups), race/ethnicity, sex,
and calendar period (2003–2006 and
2007–2008). Exposure covariates
included age at enrollment, sex, race/
ethnicity, 2002 household income level,
education level, smoking status,
enrollment source (identified by
employers, government agencies, and
other entities or by an outreach
campaign), and history of asthma,
cardiovascular disease, stroke,
emphysema, or diabetes reported at
enrollment. But other potential
confounders, such as family cancer
history and occupational exposures
prior to September 11, 2001, were not
measured. The study by Li et al. [2012]
is prone to selection bias because
enrollment in the Registry was
voluntary. The authors attempted to
mitigate this bias by restricting the
analyses to individuals without prior
invasive cancer history documented in
any of the 11 state cancer registries and
focusing on cancer incidence from 2007
to 2008. Self-reported 9/11 exposures
may be subject to recall error. Cancer
cases identified through linkages with
30 SIR is a mathematical expression that compares
the incidence experience between the population
under study and the experience of that population
had they had the same incidence experience of a
comparison population.
E:\FR\FM\24SER1.SGM
24SER1
khammond on DSKJM1Z7X2PROD with RULES
49958
Federal Register / Vol. 84, No. 185 / Tuesday, September 24, 2019 / Rules and Regulations
state cancer registries might be
underestimated, especially among those
without a known Social Security
number because a percentage of Registry
enrollees did not provide one. The
findings on rescue/recovery workers
may also be prone to the healthy worker
effect.
Li et al. [2016] updated their 2012
study, discussed above, which
evaluated excess cancer among WTC
Health Registry enrollees. In the 2016
update, the authors added 3 years of
follow-up to allow for 10 years of cancer
latency since the WTC-related
exposures. The 2016 study recalibrated
the definition of ‘‘WTC disaster physical
exposures’’ to emphasize potential
contaminants containing carcinogens.
The analysis focused on cancers
occurring from 2007 through 2011. The
study included a total of 60,339 eligible
individuals, including 24,863 rescue/
recovery workers (5,015 women) and
35,476 survivors not involved in rescue/
recovery (18,845 women). The authors
identified cancers by linkage to 11 state
cancer registries based on the state of
residence of the cohort member, and
based expected numbers of cancers on
overall New York State rates and
person-years of follow-up during 2007–
2011, adjusted for age (5-year groups),
race/ethnicity, sex, and calendar period
(2007–2011). The study found that
overall cancer incidence was
significantly greater than the reference
(non-9/11-exposed) population among
both rescue/recovery workers (SIR =
1.11, 95% CI 1.03–1.20) and survivors
(SIR = 1.08, 95% CI 1.02–1.15). Uterine
cancer incidence was not significantly
elevated among rescue/recovery workers
nor among survivors (observed uterine
cancers = 8, SIR = 0.82, 95% CI 0.35–
1.62 and observed uterine cancers = 37,
SIR = 1.03, 95% CI 0.72–1.41,
respectively). Comparisons among
exposure groups were not reported for
uterine cancer. In internal analyses,
hazard ratios and 95% CI were adjusted
for age at enrollment, sex, race/
ethnicity, smoking, education, income,
and history of a serious non-malignant
medical condition; however, findings
for uterine cancer were not reported.
Other potential confounders were not
measured. This study was prone to
selection bias, because enrollment in the
Registry was voluntary; the authors
attempted to mitigate this bias by
restricting the analyses to individuals
without prior invasive cancer history
documented in any of the 11 state
cancer registries and focusing on cancer
incidence from 2007 through 2011. In
addition, findings on rescue/recovery
VerDate Sep<11>2014
15:47 Sep 23, 2019
Jkt 247001
workers may also be subject to the
healthy worker effect.
Solan et al. [2013] conducted a cancer
incidence study among 20,984 nonFDNY WTC Health Program members
(3,203 women) involved in rescue,
recovery, and cleanup efforts at Ground
Zero after 9/11. The authors identified
cancer cases through linkage with the
tumor registries in the four states in
which 98 percent of WTC responders
resided at time of enrollment in the
Program. Self-reported exposures were
categorized based on four variables: PreSeptember 11, 2001 occupation, extent
of exposure to the dust cloud on
September 11, 2001, duration of time
spent working at the site, and work on
the debris pile during four periods
(September 2001, October 2001,
November–December 2001, and
January–June 2002). An integrated
exposure variable was created using a 4point scale (very high, high,
intermediate, and low) based on total
time spent working at Ground Zero,
exposure to the dust cloud, and work on
the debris pile. The authors obtained
vital status through linkage with the
NDI and next-of-kin reports. Expected
numbers of cancer cases were calculated
based on state rates (for New York, New
Jersey, and Connecticut residents) and
national rates (for Pennsylvania
residents) according to age (in 5-year
groups), sex, and race/ethnicity for each
year at risk. The observed and expected
numbers of cancers were used to
calculate SIRs. The SIR among study
participants was elevated and
statistically significant for all cancer
sites combined (SIR = 1.15; 95%
confidence interval (CI), 1.06–1.25).
Fewer than six cases of uterine cancer
were observed, and no additional
information was reported for this type of
cancer. Furthermore, no SIRs were
reported for uterine cancer nor were risk
ratios reported for the association
between 9/11 exposure variables and
uterine cancer. Certain potential
confounders, such as family cancer
history, were not measured. The study
is also prone to selection bias, because
enrollment in the WTC Health Program
is voluntary. Although the authors used
all available exposure metrics, relative
risk was not reported for the association
between 9/11 exposure variables and
uterine cancer. This study may also be
subject to the healthy worker effect,
which puts this population at a lower
risk of cancer compared to the general
population.
Kleinman et al. [2015] investigated
cancer incidence in 39,946 police
officers employed by the New York City
Police Department (NYPD) on
September 11, 2001 (6,366 women),
PO 00000
Frm 00018
Fmt 4700
Sfmt 4700
followed during the time periods 1995
to 2000 and 2002 to 2014. The authors
reported a 44 percent increase in the
overall median age-adjusted incidence
rate for all cancers, but no increase in
the overall median age-adjusted
incidence rates for either malignant
neoplasms of the uterus, unspecified
part (based on two cases diagnosed pre9/11 and zero cases diagnosed post-9/
11) or uterine adenosarcomas (based on
zero cases diagnosed pre-9/11 and three
cases post-9/11). This study is limited
by the inherent problems with its design
(i.e., the effects of age, time period, and
cohort parameters are intertwined in a
manner which complicates study
interpretation); the study is further
limited by the small number of cancer
cases observed as well as the absence of
information regarding participants’
presence in the dust cloud and the dates
and duration of their 9/11 exposures.
Stein et al. [2016] conducted a
mortality study of 28,918 rescue/
recovery workers (4,286 women)
enrolled in the WTC Health Program
between July 16, 2002, and December
31, 2011. The authors were aware that
16,177 WTC responders were alive due
to follow-up visits after the end of 2011,
and therefore linked the remainder (n =
12,741) to the National Death Index
(NDI). Mortality information from the
NDI was supplemented by next-of-kin
report. Similar to the study by Solan et
al. [2013], discussed above, the authors
of this study created an integrated
exposure variable using a 4-point scale
(very high, high, intermediate, and low)
based on total time spent working at
Ground Zero, exposure to the dust
cloud, and work on the debris pile.
SMRs were standardized for age (5-year
groups), sex, race, and calendar year to
compare all-cause and cause-specific
mortality among responders with
mortality in the U.S. general population.
Hazard ratios were adjusted for age on
September 11, 2001, pre-September 11,
2001 occupation, sex, race/ethnicity,
year of WTC Health Program
enrollment, smoking, and measured
body mass index. Overall mortality in
this cohort was statistically significantly
decreased (SMR = 0.43; 95% CI, 0.39–
0.48), although an overall cancer SMR
was not reported. Most cancer sitespecific SMRs were significantly
decreased; however, the SMR for cancer
of the female genital organs was
decreased but was not statistically
significant (SMR = 0.65, 95% CI 0.08–
2.37) and was based on only two deaths.
An SMR for uterine cancer was not
provided, neither were hazard ratios for
the association between WTC-related
exposure variables and mortality from
E:\FR\FM\24SER1.SGM
24SER1
Federal Register / Vol. 84, No. 185 / Tuesday, September 24, 2019 / Rules and Regulations
uterine cancer. Some potential
confounders, such as family cancer
history, were not measured. The study
is prone to selection bias because
enrollment in the WTC Health Program
was voluntary. Social Security numbers
were available for only 37 percent of the
records sent to NDI for linkage, limiting
the quality of the matches. The healthy
worker effect may put this population at
a lower risk of cancer compared to the
general population.
Quantity and Quality Review of
Relevant Studies
khammond on DSKJM1Z7X2PROD with RULES
The quantity and quality of these
seven studies were reviewed together to
examine whether the available evidence
has the potential to provide a basis for
a decision on whether to add uterine
cancer, including endometrial cancer, to
the List. Prospective cohort studies, like
those described above, have the
advantage that study participants are
considered to be disease-free at the
beginning of the observation period
when their exposure occurred;
therefore, in such studies it is often
possible to establish the temporal
sequence between exposure and
outcome. Cancer studies, however,
present unique concerns since some
cancers become apparent only after long
periods of time following exposure.31
This latency effect means it is possible
that a cancer may have been present but
undetected prior to September 11, 2001.
In addition, all of the studies described
above have had a relatively short period
of follow-up since September 11, 2001.
The size and makeup of the cohorts
studied may also limit the usefulness of
the studies. The studies discussed above
may not have the necessary statistical
power to detect excesses in uterine
cancer, due to the small number of
females in the cohort. This is especially
a concern with studies of 9/11-exposed
rescue/recovery workers since those
cohorts are not sizeable and only
approximately 15 percent female.
Moreover, the overlap in participation
in the studies may limit the
interpretation of consistency of findings
31 This delay between environmental exposure
and onset of cancer symptoms is referred to as the
‘‘cancer latency period.’’ For more information
about latency for cancers and how the WTC Health
Program has addressed this issue, please see
Minimum Latency & Types or Categories of Cancer,
Jan. 6, 2015, https://www.cdc.gov/wtc/pdfs/policies/
WTCHP-Minimum-Cancer-Latency-PP–01062015–
508.pdf.
VerDate Sep<11>2014
15:47 Sep 23, 2019
Jkt 247001
among the studies. Approximately 20
percent of 9/11-exposed rescue/recovery
workers enrolled in the WTC Health
Program are also enrolled in the WTC
Health Registry. These two cohorts also
may be prone to selection bias, because
enrollment in the respective programs
was voluntary. For the WTC Health
Registry cohort, it is possible that
differential participation due to race/
ethnicity, socioeconomic status, age, or
their perception of being affected by the
9/11 attacks, may have occurred. For the
rescue/recovery worker cohort enrolled
in the WTC Health Program, their health
status, including their cancer diagnosis,
may have prompted them to enroll. A
strength of these studies is that findings
are available for both 9/11-exposed
rescue/recovery workers as well as
survivors.
The relevant studies published to
date, and reviewed above, do not
provide consistent evidence that uterine
cancer, including endometrial cancer,
incidence or mortality is elevated
among WTC responders and/or
survivors. In addition, the studies did
not report a dose-response relationship
between WTC-related exposures and
uterine cancer, including endometrial
cancer. Taken together, these studies do
not have sufficient quality and quantity
to demonstrate a potential to provide a
basis for a decision on whether to add
uterine cancer, including endometrial
cancer, to the List. Accordingly, these
studies are not further reviewed.
Administrator Determination
Upon review of the evidence available
in peer-reviewed, published,
epidemiological studies and updates
regarding uterine cancer, including
endometrial cancer, among 9/11exposed populations, the Administrator
has determined that the available
evidence does not have the potential to
provide a basis for deciding whether to
propose adding uterine cancer,
including endometrial cancer, to the
List. Accordingly, the Administrator has
not directed the Program to assess the
available evidence using Methods 1, 2,
or 3, nor has he directed the Program to
request advice from the STAC pursuant
to Method 4, discussed above.
The WTC Health Program may
consider uterine cancer, including
endometrial cancer, to be a condition
medically associated with a certified
WTC-related health condition in
individual cases. Program members who
PO 00000
Frm 00019
Fmt 4700
Sfmt 4700
49959
think their uterine or endometrial
cancer is a side effect of treatment of a
certified WTC-related health condition
should ask their WTC Health Program
medical provider whether their
endometrial cancer might be considered
a medically associated health condition.
E. Administrator’s Final Decision on
Whether To Propose the Addition of
Uterine Cancer, Including Endometrial
Cancer, to the List
Pursuant to PHS Act, sec.
3312(a)(6)(B)(iv) and 42 CFR
88.16(a)(2)(iv), the Administrator has
determined that insufficient evidence is
available to take further action at this
time, including proposing the addition
of uterine cancer, including endometrial
cancer, to the List (pursuant to PHS Act,
sec. 3312(a)(6)(B)(ii) and 42 CFR
88.16(a)(2)(ii)) or publishing a
determination not to publish a proposed
rule in the Federal Register (pursuant to
PHS Act, sec. 3312(a)(6)(B)(iii) and 42
CFR 88.16(a)(2)(iii)). The Administrator
has also determined that requesting a
recommendation from the STAC
(pursuant to PHS Act, sec.
3312(a)(6)(B)(i) and 42 CFR
88.16(a)(2)(i)) is unwarranted.
For the reasons discussed above, the
Petition 023 request to add endometrial
cancer to the List of WTC-Related
Health Conditions is denied.
F. Approval To Submit Document to the
Office of the Federal Register
The Secretary, HHS, or his designee,
the Director, Centers for Disease Control
and Prevention (CDC) and
Administrator, Agency for Toxic
Substances and Disease Registry
(ATSDR), authorized the undersigned,
the Administrator of the WTC Health
Program, to sign and submit the
document to the Office of the Federal
Register for publication as an official
document of the WTC Health Program.
Robert Redfield M.D., Director, CDC,
and Administrator, ATSDR, approved
this document for publication on
September 12, 2019.
John J. Howard,
Administrator, World Trade Center Health
Program and Director, National Institute for
Occupational Safety and Health, Centers for
Disease Control and Prevention, Department
of Health and Human Services.
[FR Doc. 2019–20364 Filed 9–23–19; 8:45 am]
BILLING CODE 4163–18–P
E:\FR\FM\24SER1.SGM
24SER1
Agencies
[Federal Register Volume 84, Number 185 (Tuesday, September 24, 2019)]
[Rules and Regulations]
[Pages 49954-49959]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-20364]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
42 CFR Part 88
[NIOSH Docket 094]
World Trade Center Health Program; Petition 023--Uterine Cancer,
Including Endometrial Cancer; Finding of Insufficient Evidence
AGENCY: Centers for Disease Control and Prevention, HHS.
ACTION: Denial of petition for addition of a health condition.
-----------------------------------------------------------------------
SUMMARY: On April 23, 2019, the Administrator of the World Trade Center
(WTC) Health Program received a petition (Petition 023) to add
``endometrial cancer'' to the List of WTC-Related Health Conditions
(List). Upon reviewing the scientific and medical literature, including
information provided by the petitioner, the Administrator has
determined that the available evidence does not have the potential to
provide a basis for a decision on whether to add the major site uterine
cancer, including its subtype, endometrial cancer, to the List. The
Administrator also finds that insufficient evidence exists to request a
recommendation of the WTC Health Program Scientific/Technical Advisory
Committee (STAC), to publish a proposed rule, or to publish a
determination not to publish a proposed rule.
DATES: The Administrator of the WTC Health Program is denying this
petition for the addition of a health condition as of September 24,
2019.
ADDRESSES: Visit the WTC Health Program website at https://www.cdc.gov/wtc/received.html to review Petition 023.
FOR FURTHER INFORMATION CONTACT: Rachel Weiss, Program Analyst, 1090
Tusculum Avenue, MS: C-48, Cincinnati, OH 45226; telephone (855) 818-
1629 (this is a toll-free number); email [email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
A. WTC Health Program Statutory Authority
B. Procedures for Evaluating a Petition for Cancer
C. Petition 023
D. Assessment of Scientific and Medical Information
E. Administrator's Final Decision on Whether To Propose the Addition
of Uterine Cancer, Including Endometrial Cancer, to the List
F. Approval To Submit Document to the Office of the Federal Register
A. WTC Health Program Statutory Authority
Title I of the James Zadroga 9/11 Health and Compensation Act of
2010 (Pub. L. 111-347, as amended by Pub. L. 114-113), added Title
XXXIII to the Public Health Service (PHS) Act,\1\ establishing the WTC
Health Program within the Department of Health and Human Services
(HHS). The WTC Health Program provides medical monitoring and treatment
benefits for health conditions on the List to eligible firefighters and
related personnel, law enforcement officers, and rescue, recovery, and
cleanup workers who responded to the September 11, 2001, terrorist
attacks in New York City, at the Pentagon, and in Shanksville,
Pennsylvania (responders), and to eligible persons who were present in
the dust or dust cloud on September 11, 2001, or who worked, resided,
or attended school, childcare, or adult daycare in the New York City
disaster area (survivors).
---------------------------------------------------------------------------
\1\ Title XXXIII of the PHS Act is codified at 42 U.S.C. 300mm
to 300mm-61. Those portions of the James Zadroga 9/11 Health and
Compensation Act of 2010 found in Titles II and III of Public Law
111-347 do not pertain to the WTC Health Program and are codified
elsewhere.
---------------------------------------------------------------------------
All references to the Administrator of the WTC Health Program
(Administrator) in this document mean the Director of the National
Institute for Occupational Safety and Health (NIOSH) or his designee.
Pursuant to section 3312(a)(6)(B) of the PHS Act, interested
parties may petition the Administrator to add a health condition to the
List in 42 CFR 88.15. Within 90 days after receipt of a valid petition
to add a condition to the List, the Administrator must take one of the
following four actions described in section 3312(a)(6)(B) of the PHS
Act and Sec. 88.16(a)(2) of the Program regulations: (1) Request a
recommendation of the STAC, (2) publish a proposed rule in the Federal
Register to add such health condition, (3) publish in the Federal
Register the Administrator's determination not to publish such a
proposed rule and the basis for such determination, or (4) publish in
the Federal Register a determination that insufficient evidence exists
to take action under (1) through (3) above.
B. Procedures for Evaluating a Petition for Cancer
In addition to the regulatory provisions, the WTC Health Program
has developed policies to guide the
[[Page 49955]]
review of submissions and petitions,\2\ as well as the analysis of
evidence supporting the potential addition of a type of cancer to the
List.\3\
---------------------------------------------------------------------------
\2\ See WTC Health Program [2014], Policy and Procedures for
Handling Submissions and Petitions to Add a Health Condition to the
List of WTC-Related Health Conditions, May 14, 2014, https://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf.
\3\ See WTC Health Program [2019], Policy and Procedures for
Adding Types of Cancer to the List of WTC-Related Health Conditions,
May 1, 2019, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Addition_of_Cancer_Policy_UPDATED_050719-508.pdf.
---------------------------------------------------------------------------
A valid petition must include sufficient medical basis for the
association between the September 11, 2001, terrorist attacks and the
health condition to be added; in accordance with WTC Health Program
policy, reference to a peer-reviewed, published, epidemiologic study
about the health condition among 9/11-exposed populations or to
clinical case reports of health conditions in WTC responders or
survivors may demonstrate the required medical basis.\4\ Studies
linking 9/11 agents \5\ or hazards to the petitioned health condition
may also provide sufficient medical basis for a valid petition.
---------------------------------------------------------------------------
\4\ See supra note 2.
\5\ 9/11 agents are chemical, physical, biological, or other
hazards reported in a published, peer-reviewed exposure assessment
study of responders, recovery workers, or survivors who were present
in the New York City disaster area, or at the Pentagon site, or the
Shanksville, Pennsylvania site, as those locations are defined in 42
CFR 88.1, as well as those hazards not identified in a published,
peer-reviewed exposure assessment study, but which are reasonably
assumed to have been present at any of the three sites. See WTC
Health Program [2018], Development of the Inventory of 9/11 Agents,
July 17, 2018, https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf.
---------------------------------------------------------------------------
After the Program has determined that a petition is valid, the
Administrator must direct the Program to conduct a systematic
literature search (a keyword search of relevant scientific databases)
to gather information about the following: (1) Studies about the type
of cancer requested to be added to the List among 9/11-exposed
populations, (2) studies showing a potential causal association between
the requested cancer and a health condition on the List, and (3)
classifications of the World Health Organization's International Agency
for Research on Cancer (IARC) and the National Toxicology Program (NTP)
Report on Carcinogens relevant to the requested cancer. Peer-reviewed,
published, epidemiologic studies of the cancer in 9/11-exposed
populations are considered relevant. The quantity and quality of
relevant studies are reviewed for their potential to provide a basis
for deciding whether to propose adding the type of cancer to the List.
If the Program determines that the relevant studies have the
potential to provide a basis for deciding whether to propose adding the
type of cancer to the List, the cancer type may be added to the List if
one of the four following methods is met:
Method 1. Epidemiologic Studies of September 11, 2001-Exposed
Populations.
The peer-reviewed, published, epidemiologic studies of 9/11-
exposed populations are assessed by applying the following criteria
extrapolated from the Bradford Hill criteria, as appropriate:
a. Strength of the association between a 9/11 exposure and a
type of cancer (including the precision of the risk estimate \6\),
---------------------------------------------------------------------------
\6\ A precision of the risk estimate describes the uncertainty
inherent in estimating the strength of association (the effect size)
between exposure and health effect from observational data. It is
expressed as a confidence interval illustrating a range of values
that contains the true effect size. A narrow confidence interval
indicates a more precise measure of the effect size and a wider
interval indicates greater uncertainty.
---------------------------------------------------------------------------
b. Consistency of the findings across multiple studies. If only
a single published epidemiologic study is available for assessment,
the consistency of findings cannot be evaluated and more emphasis
will be placed on evaluating the strength of the association and the
precision of the risk estimate,
c. Biological gradient, or dose-response relationships between
9/11 exposures and the type of cancer, and
d. Plausibility and coherence with known facts about the biology
of the type of cancer.
Method 2. Established Causal Associations.
A type of cancer may be added to the List if there is well-
established scientific support published in multiple epidemiologic
studies for a causal association between that cancer and a condition
already on the List of WTC-Related Health Conditions.
Method 3. Review of Evaluations of Carcinogenicity in Humans.
A type of cancer may be added to the List under Method 3 if both
of the following criteria are satisfied:
3A. Published Exposure Assessment Information. A 9/11 agent
included in the Inventory of 9/11 Agents \7\ is identified, and
---------------------------------------------------------------------------
\7\ The Inventory of 9/11 Agents is composed of those agents
identified in Tables 1-4 of the document, Development of the
Inventory of 9/11 Agents. See supra note 5.
---------------------------------------------------------------------------
3B. Evaluation of Carcinogenicity in Humans from Scientific
Studies. NTP has determined that the [identified] 9/11 agent is
known to be a human carcinogen or is reasonably anticipated to be a
human carcinogen, and IARC has determined there is sufficient or
limited evidence that the 9/11 agent causes [the requested] type of
cancer.
Method 4. Review of Information Provided by the WTC Health
Program Scientific/Technical Advisory Committee.\8\
---------------------------------------------------------------------------
\8\ The WTC Health Program Scientific/Technical Advisory
Committee may be convened by the Administrator if he determines that
its advice would be helpful. See supra note 3 at Sec. V.
---------------------------------------------------------------------------
A type of cancer may be added to the List if the STAC has
provided a reasonable basis for adding a type of cancer.
If the evaluation of evidence required for any of the four methods
demonstrates that the criteria in that method are satisfied, the
Administrator will propose the addition of the type of cancer to the
List.
C. Petition 023
On April 23, 2019, the Administrator received a petition (Petition
023) requesting the addition of ``endometrial cancer'' to the List.\9\
The petition included a 2002 study by Lioy et al.\10\ and a 2017 study
by McElroy et al.\11\ which together provided sufficient medical basis
for the petition to be considered valid because they demonstrate the
presence of 9/11 agents, including cadmium, at the WTC site and that
cadmium exposure is associated with a statistically significant
increase in endometrial cancer risk. However, because neither Lioy et
al. [2002] nor McElroy et al. [2017] is a peer-reviewed, published,
epidemiologic study of endometrial cancer (or the major site, uterine
cancer) in a 9/11-exposed population, neither study is considered
relevant nor are they further reviewed in this action.
---------------------------------------------------------------------------
\9\ See Petition 023, WTC Health Program: Petitions Received,
https://www.cdc.gov/wtc/received.html.
\10\ Lioy PJ, Weisel CP, Millette JR, Eisenreich S, Vallero D,
Offenberg J, Turpin B, Zhong M, Cohen MD, Prophete C, Yang I, Stiles
R, Chee G, Johnson W, Porcja R, Alimokhtari S, Hale RC, Weschler C,
Chen LC [2002], Characterization of the Dust/Smoke Aerosol that
Settled East of the World Trade Center (WTC) in Lower Manhattan
after the Collapse of the WTC11 September 2001, Environ Health
Perspect 110(7), 703-714.
\11\ McElroy JA, Kruse RL, Guthrie J, Gangnon RE, Robertson JD
[2017], Cadmium Exposure and Endometrial Cancer Risk: A Large
Midwestern U.S. Population-Based Case-Control Study, PLoS ONE 12(7):
e0179360.
---------------------------------------------------------------------------
In the Program's List of WTC-Related Health Conditions, types of
cancer are identified by the major cancer site/histology groups that
are commonly used in the reporting of cancer incidence data, using the
groupings standardized by the National Cancer Institute's Surveillance,
Epidemiology and End Results Program (SEER) for national cancer
surveillance.\12\ Cancer subtypes are not included in the List. Because
endometrial cancer is a subtype of uterine cancer,\13\ the Program has
[[Page 49956]]
determined that the scope of this petition and subsequent Program
review should include both endometrial cancer and the major site,
uterine cancer.
---------------------------------------------------------------------------
\12\ National Cancer Institute [2008], Surveillance Epidemiology
and End Results: Site Recode ICD-O-3/WHO 2008 Definition, https://seer.cancer.gov/siterecode/icdo3_dwhoheme//.
\13\ Endometrial cancer develops in the lining of the uterus,
called the endometrium. Although endometrial uterine cancer is the
most common type of uterine cancer, accounting for more than 90
percent of cases, there are other types of uterine cancer. See
https://www.cancer.gov/types/uterine/patient/endometrial-treatment-pdq.
---------------------------------------------------------------------------
D. Assessment of Scientific and Medical Information
In response to Petition 023, the Program conducted both a
systematic literature search to identify peer-reviewed, published
studies of uterine cancer, including endometrial cancer, in 9/11-
exposed women, as well as a review of NTP and IARC classifications of
9/11 agents, including those 9/11 agents identified by IARC as
carcinogenic agents with sufficient or limited evidence that the agent
causes uterine cancer, including endometrial cancer, in humans.\14\ The
National Cancer Institute has not identified any of the health
conditions on the List of WTC-Related Health Conditions as known risk
factors for uterine or endometrial cancer; therefore, a systematic
literature search for studies regarding a causal association between
uterine or endometrial cancer and a health condition on the List was
not conducted.\15\
---------------------------------------------------------------------------
\14\ Databases searched include: CINAHL, Embase, NIOSHTIC-2,
ProQuest Health & Safety, PsycINFO, Ovid MEDLINE, Scopus, Toxicology
Abstracts/TOXLINE, and WTC Health Program Bibliographic Database.
Keywords used to conduct the search include: Endometrial neoplasm,
endometrial cancer, endometrial carcinoma, malignant neoplasm of
endometrium, adenocarcinoma of endometrium, cancer of the
endometrium, Uterine Neoplasm, malignant neoplasm of corpus uteri,
uterine cancer, uterine carcinoma. The literature search was
conducted in English-language journals on May 23, 2019.
\15\ No health conditions on the List of WTC-Related Health
Conditions are known risk factors for uterine cancer. See https://www.cancer.gov/types/uterine/hp/endometrial-prevention-pdq.
---------------------------------------------------------------------------
Literature Search Results
Two publications were identified in the search for studies
specifically regarding uterine cancer, including endometrial cancer,
among 9/11-exposed populations, thus meeting the Program's criteria for
further evaluation: Li et al. [2012] \16\ and its update Li et al.
[2016].\17\ In addition to the two Li et al. publications found in the
literature search, the Program was aware of additional studies
examining all types of cancer in 9/11-exposed subpopulations (rescue
and recovery workers and survivors); these additional studies were also
reviewed to determine whether they may provide further insight into
cancer incidence and mortality applicable to the evaluation of uterine
cancer, including endometrial cancer: Jordan et al. [2011] \18\ and its
update Jordan et al. [2018],\19\ Zeig-Owens et al. [2011] \20\ and its
update Moir et al. [2016],\21\ Solan et al. [2013],\22\ Kleinman et al.
[2015],\23\ and Stein et al. [2016].\24\ Of the additional studies,
only Zeig-Owens et al. [2011] and its update Moir et al. [2016] were
found not to be relevant (they were not peer-reviewed, published,
studies of uterine or endometrial cancer in the 9/11-exposed
population) because neither addressed cancers in female WTC responders.
The other five additional studies, along with Li et al. [2012] and Li
et al. [2016], were found to be relevant and were reviewed for quantity
and quality, below.
---------------------------------------------------------------------------
\16\ Li J, Cone JE, Kahn AR, Brackbill RM, Farfel MR, Greene CM,
Hadler JL, Stayner LT, Stellman SD [2012], Association between World
Trade Center Exposure and Excess Cancer Risk, JAMA 308(23):2479-88.
\17\ Li J, Brackbill RM, Liao TS, Qiao B, Cone JE, Farfel MR,
Hadler JL, Kahn AR, Konty KJ, Stayner LT, Stellman SD [2016], Ten-
Year Cancer Incidence in Rescue/Recovery Workers and Civilians
Exposed to the September 11, 2001 Terrorist Attacks on the World
Trade Center, Am J Ind Med 59(9):709-21.
\18\ Jordan HT, Brackbill RM, Cone JE, Debcoudhury I, Farfel MR,
Greene CM, Hadler JL, Kennedy J, Li J, Liff J, Stayner L, Stellman
SD [2011], Mortality among Survivors of the Sept 11, 2001, World
Trade Center Disaster: Results from the World Trade Center Health
Registry Cohort, Lancet 378(9794):879-87.
\19\ Jordan HT, Stein CR, Li J, Cone JE, Stayner L, Hadler JL,
Brackbill RM, Farfel MR [2018], Mortality among Rescue and Recovery
Workers and Community Members Exposed to the September 11, 2001
World Trade Center Terrorist Attacks, 2003-2014, Environ Res
163:270-9.
\20\ Zeig-Owens R, Webber MP, Hall CB, Schwartz T, Jaber N,
Weakley J, Rohan TE, Cohen HW, Derman O, Aldrich TK, Kelly K,
Prezant DJ [2011], Early Assessment of Cancer Outcomes in New York
City Firefighters after the 9/11 Attacks: an Observational Cohort
Study, Lancet 378(9794):898-905.
\21\ Moir W, Zeig-Owens R, Daniels RD, Hall CB, Webber MP, Jaber
N, Yiin JH, Schwartz T, Liu X, Vossbrinck M, Kelly K, Prezant D
[2016], Post-9/11 Cancer Incidence in World Trade Center-Exposed New
York City Firefighters as Compared to a Pooled Cohort of
Firefighters from San Francisco, Chicago and Philadelphia (9/11/
2001-2009), Am J Ind Med 59(9):722-30.
\22\ Solan S, Wallenstein S, Shapiro M, Teitelbaum SL, Stevenson
L, Kochman A, Kaplan J, Dellenbaugh C, Kahn A, Biro FN, Crane M,
Crowley L, Gabrilove J, Gonsalves L, Harrison D, Herbert R, Luft B,
Markowitz SB, Moline J, Niu X, Sacks H, Shukla G, Udasin I, Lucchini
RG, Boffetta P, Landrigan PJ [2013], Cancer Incidence in World Trade
Center Rescue and Recovery Workers, 2001-2008, Environ Health
Perspect 21(6):699-704.
\23\ Kleinman EJ, Christos PJ, Gerber LM, Reilly JP, Moran WF,
Einstein AJ, Neugut AI [2015], NYPD Cancer Incidence Rates 1995-2014
Encompassing the Entire World Trade Center Cohort, J Occup Environ
Med 57(10):e101-13.
\24\ Stein CR, Wallenstein S, Shapiro M, Hashim D, Moline JM,
Udasin I, Crane MA, Luft BJ, Lucchini RG, Holden WL [2016],
Mortality among World Trade Center Rescue and Recovery Workers,
2002-2011, Am J Ind Med 59(2):87-95.
---------------------------------------------------------------------------
The Program reviewed the NTP Report on Carcinogens \25\ and found
that twelve 9/11 agents \26\ are known to be human carcinogens and
twenty-seven 9/11 agents are reasonably anticipated to be human
carcinogens. \27\ However, IARC has not determined that any of these
thirty-nine 9/11 agents demonstrate sufficient or limited evidence of a
causal association with uterine or endometrial cancer in humans.\28\
---------------------------------------------------------------------------
\25\ National Toxicology Program, HHS [2016], Report on
Carcinogens, 14th Edition (Research Triangle Park, NC). https://ntp.niehs.nih.gov/go/roc14.
\26\ As identified in the Inventory of 9/11 Agents, see supra
notes 7 and 5.
\27\ The 39 total 9/11 agents identified by NTP are as follows:
Arsenic, Asbestos, Benzene, Beryllium, 1,3-Butadiene, Cadmium,
Nickel, Silica, Solar Radiation, Soot, Sulfuric Acid,
Trichloroethylene (Known To Be Human Carcinogens); as well as
Acetaldehyde, Acrylonitrile, Benz[a]anthracene,
Benzo[k]fluoranthene, Benzo[a]pyrene, Carbon Tetrachloride,
Chloroform, Cobalt, Dibenz[a,h]anthracene, 1,4-Dichlorobenzene,
Dichlorodiphenyltrichloroethane, 1,2-Dichloroethane,
Dichloromethane, 1,3-Dichloropropene, Diesel Exhaust Particulates,
1,4-Dioxane, Hexachlorobenzene, Lead, Hexachlorocyclohexane, Mirex,
Naphthalene, Nickel, Polybrominated Biphenyls, Polychlorinated
Biphenyls, Styrene, Tetrachloroethylene, and Toluene Diisocyanates
(Reasonably Anticipated To Be Human Carcinogens).
\28\ International Agency for Research on Cancer [1976], IARC
Monographs on the Evaluation of Carcinogenic Risk of Chemicals to
Man: Cadmium, Nickel, Some Epoxides, Miscellaneous Industrial
Chemicals and General Considerations on Volatile Anesthetics, Volume
11; Lyon, France.
---------------------------------------------------------------------------
Review of Relevant Studies
The studies identified as relevant during the literature review
process were further assessed to determine whether they have sufficient
quality and quantity to demonstrate a potential to support the addition
of uterine cancer, including endometrial cancer. The relevant studies
introduced above are described below, including a description of their
respective strengths and limitations.
Jordan et al. [2011] conducted a mortality study among the cohort
of WTC Health Registry enrollees that included 13,337 rescue/recovery
workers (3,188 women) and 28,593 survivors (16,733 women) living in New
York City at the time of their enrollment. The authors identified
deaths occurring in 2003-2009 through linkage to New York City vital
records and the National Death Index (NDI). Standardized mortality
ratios (SMRs) were calculated with New York City rates from 2000 to
2009 as the reference. Within the cohort, proportional hazards were
used to examine the relation between WTC-related exposure levels (high,
intermediate, or low for each group, based on exposure to the dust
cloud, and time and duration working on the pile) and all-cause
mortality, but not mortality for specific cancers. All-
[[Page 49957]]
cause SMRs were significantly lower than that expected for rescue/
recovery workers (SMR = 0.45, 95% CI (confidence interval) 0.38-0.53)
and survivors (SMR = 0.61, 95% CI 0.56-0.66). There were no
significantly elevated SMRs for any category of cancer examined,
including cancer of female genital organs, among all studied Registry
enrollees (SMR = 0.82, 95% CI 0.49-1.28), rescue/recovery workers (SMR
= 0.67, 95% CI 0.08-2[middot]43), or survivors (SMR = 0.84, 95% CI
0.49-1.35). Separate SMRs for cancer of specific types of female
genital organs, including uterine cancer, were not provided. SMRs were
adjusted for age, sex, race, and calendar year. Adjusted hazard ratios
(AHRs) were adjusted for age, sex, race and ethnic origin, income,
smoking, and, for survivors, Registry recruitment source. This study's
limitations include possible selection bias, since enrollment in the
Registry is voluntary. Exposure reporting may also be subject to recall
error because 9/11 exposures were self-reported 2 to 3 years after the
September 11, 2001 terrorist attacks and subsequent clean-up of the
sites. The healthy worker effect puts the population of rescue/recovery
workers at a lower risk of cancer compared to the general
population,\29\ which includes persons who are chronically ill,
hospitalized, or otherwise unemployable. In addition, other potential
confounders, such as family cancer history and occupational exposures
prior to September 11, 2001, were not measured.
---------------------------------------------------------------------------
\29\ The healthy worker effect is a form of selection bias
``typically seen in observational studies of occupational exposures
with improper choice of comparison group (usually general
population).'' See Chowdhury R, Shah D, Payal AR, [2017], Healthy
Worker Effect Phenomenon: Revisited with Emphasis on Statistical
Methods--A Review, Indian J Occup Environ Med 21(1), 2-8.
---------------------------------------------------------------------------
Jordan et al. [2018] updated their 2011 study, discussed above, by
including the full cohort of WTC Health Registry enrollees, not only
those living in New York City at time of enrollment, and adding 5 years
of follow-up. The 2018 update included 29,280 rescue/recovery workers
(6,422 women) and 39,643 survivors (21,126 women). The authors used New
York City population mortality rates from 2003 to 2012 as the primary
reference, and also conducted a secondary analysis using U.S.
population comparison rates from 2003 to 2011. Proportional hazards
were used to examine the relation between WTC-related exposure levels
(high, intermediate, or low for each group, based on time and duration
in lower Manhattan) and total mortality, as well as overall cancer
mortality, but not mortality for specific cancer types. Overall cancer
SMRs were not elevated for rescue/recovery workers (SMR = 0.94, 95% CI
0.84-1.05), but were significantly elevated among survivors (SMR =
1.14, 95% CI 1.06-1.24) when compared to the New York City population;
no elevated SMRs were reported for all cancers using the general U.S.
population as reference. Cancers of the female genital organs were not
significantly elevated among rescue/recovery workers or survivors
(observed deaths = 7, SMR = 0.67, 95% CI 0.27-1.39 and observed deaths
= 43, SMR = 1.17, 95% CI 0.85-1.58, respectively). The authors also
examined 119 sub-categories of the major causes of death, but only
reported statistically significant results; uterine cancers were not
among the reported causes of death, suggesting that the risk of uterine
cancer was not significantly elevated. No statistically significant
elevations and no significant trends were observed in the analyses of
the association between WTC-related exposures and overall cancer
mortality. Like the previously reviewed study, Jordan et al. [2018] is
prone to selection bias, because enrollment in the Registry was
voluntary. Further, 9/11 exposures were self-reported 2 to 3 years
after the September 11, 2001 terrorist attacks, and thus are subject to
recall error. The healthy worker effect may put the population of
rescue/recovery workers at a lower risk of cancer compared with the
general population. An analogous effect has been seen in people who
volunteer for health studies and might have contributed to the low
relative mortality in both the rescue/recovery and survivor
participants. As in the previously described study, other potential
confounders, such as family cancer history and occupational exposures
prior to September 11, 2001, were not measured.
Li et al. [2012] conducted a cancer incidence study among enrollees
in the WTC Health Registry who were residents of New York State on
September 11, 2001, and had no history of cancer at the time of
enrollment. A total of 55,778 individuals were eligible for the study,
including 21,850 involved in rescue/recovery (4,185 women) and 33,928
survivors not involved in rescue/recovery (18,922 women). The authors
identified cancers by linkage to 11 state cancer registries based on
the state of residence of the cohort member, and based expected numbers
of cancers on New York State cancer rates. They used qualitative
descriptions of 9/11 exposures to classify Registry enrollee exposure
as high, intermediate, or low based on time and duration in lower
Manhattan. The authors conducted separate analyses for rescue/recovery
workers and for survivors, and presented separate results for the
period of enrollment through 2006 (early period) and 2007 through 2008
(later period). Among rescue/recovery workers, the standardized
incidence ratio (SIR) \30\ for all cancer sites combined was not
statistically significantly elevated in either period (early period,
SIR = 0.94; 95% CI, 0.82-1.08; later period SIR = 1.14; 95% CI, 0.99-
1.30). Uterine cancer incidence was not elevated for rescue/recovery
workers during the early period (five cases or less [the precise number
of cases was not reported, likely because of restrictions on reporting
small numbers], SIR = 0.97, 95% CI 0.2-2.83), and no cases were
reported during the later period. Among survivors, no significantly
increased incidence for all cancer sites combined was observed in
either period. Uterine cancer incidence was not elevated for survivors
during the early or late periods (early: observed uterine cancers = 16,
SIR = 1.01, 95% CI 0.58-1.65 and late: observed uterine cancers = 14,
SIR = 1.01, 95% CI 0.55-1.69, respectively). Results of analyses to
assess the risk of uterine cancer as a function of 9/11 exposure levels
were not reported. SIRs were stratified by age (5-year age groups),
race/ethnicity, sex, and calendar period (2003-2006 and 2007-2008).
Exposure covariates included age at enrollment, sex, race/ethnicity,
2002 household income level, education level, smoking status,
enrollment source (identified by employers, government agencies, and
other entities or by an outreach campaign), and history of asthma,
cardiovascular disease, stroke, emphysema, or diabetes reported at
enrollment. But other potential confounders, such as family cancer
history and occupational exposures prior to September 11, 2001, were
not measured. The study by Li et al. [2012] is prone to selection bias
because enrollment in the Registry was voluntary. The authors attempted
to mitigate this bias by restricting the analyses to individuals
without prior invasive cancer history documented in any of the 11 state
cancer registries and focusing on cancer incidence from 2007 to 2008.
Self-reported 9/11 exposures may be subject to recall error. Cancer
cases identified through linkages with
[[Page 49958]]
state cancer registries might be underestimated, especially among those
without a known Social Security number because a percentage of Registry
enrollees did not provide one. The findings on rescue/recovery workers
may also be prone to the healthy worker effect.
---------------------------------------------------------------------------
\30\ SIR is a mathematical expression that compares the
incidence experience between the population under study and the
experience of that population had they had the same incidence
experience of a comparison population.
---------------------------------------------------------------------------
Li et al. [2016] updated their 2012 study, discussed above, which
evaluated excess cancer among WTC Health Registry enrollees. In the
2016 update, the authors added 3 years of follow-up to allow for 10
years of cancer latency since the WTC-related exposures. The 2016 study
recalibrated the definition of ``WTC disaster physical exposures'' to
emphasize potential contaminants containing carcinogens. The analysis
focused on cancers occurring from 2007 through 2011. The study included
a total of 60,339 eligible individuals, including 24,863 rescue/
recovery workers (5,015 women) and 35,476 survivors not involved in
rescue/recovery (18,845 women). The authors identified cancers by
linkage to 11 state cancer registries based on the state of residence
of the cohort member, and based expected numbers of cancers on overall
New York State rates and person-years of follow-up during 2007-2011,
adjusted for age (5-year groups), race/ethnicity, sex, and calendar
period (2007-2011). The study found that overall cancer incidence was
significantly greater than the reference (non-9/11-exposed) population
among both rescue/recovery workers (SIR = 1.11, 95% CI 1.03-1.20) and
survivors (SIR = 1.08, 95% CI 1.02-1.15). Uterine cancer incidence was
not significantly elevated among rescue/recovery workers nor among
survivors (observed uterine cancers = 8, SIR = 0.82, 95% CI 0.35-1.62
and observed uterine cancers = 37, SIR = 1.03, 95% CI 0.72-1.41,
respectively). Comparisons among exposure groups were not reported for
uterine cancer. In internal analyses, hazard ratios and 95% CI were
adjusted for age at enrollment, sex, race/ethnicity, smoking,
education, income, and history of a serious non-malignant medical
condition; however, findings for uterine cancer were not reported.
Other potential confounders were not measured. This study was prone to
selection bias, because enrollment in the Registry was voluntary; the
authors attempted to mitigate this bias by restricting the analyses to
individuals without prior invasive cancer history documented in any of
the 11 state cancer registries and focusing on cancer incidence from
2007 through 2011. In addition, findings on rescue/recovery workers may
also be subject to the healthy worker effect.
Solan et al. [2013] conducted a cancer incidence study among 20,984
non-FDNY WTC Health Program members (3,203 women) involved in rescue,
recovery, and cleanup efforts at Ground Zero after 9/11. The authors
identified cancer cases through linkage with the tumor registries in
the four states in which 98 percent of WTC responders resided at time
of enrollment in the Program. Self-reported exposures were categorized
based on four variables: Pre-September 11, 2001 occupation, extent of
exposure to the dust cloud on September 11, 2001, duration of time
spent working at the site, and work on the debris pile during four
periods (September 2001, October 2001, November-December 2001, and
January-June 2002). An integrated exposure variable was created using a
4-point scale (very high, high, intermediate, and low) based on total
time spent working at Ground Zero, exposure to the dust cloud, and work
on the debris pile. The authors obtained vital status through linkage
with the NDI and next-of-kin reports. Expected numbers of cancer cases
were calculated based on state rates (for New York, New Jersey, and
Connecticut residents) and national rates (for Pennsylvania residents)
according to age (in 5-year groups), sex, and race/ethnicity for each
year at risk. The observed and expected numbers of cancers were used to
calculate SIRs. The SIR among study participants was elevated and
statistically significant for all cancer sites combined (SIR = 1.15;
95% confidence interval (CI), 1.06-1.25). Fewer than six cases of
uterine cancer were observed, and no additional information was
reported for this type of cancer. Furthermore, no SIRs were reported
for uterine cancer nor were risk ratios reported for the association
between 9/11 exposure variables and uterine cancer. Certain potential
confounders, such as family cancer history, were not measured. The
study is also prone to selection bias, because enrollment in the WTC
Health Program is voluntary. Although the authors used all available
exposure metrics, relative risk was not reported for the association
between 9/11 exposure variables and uterine cancer. This study may also
be subject to the healthy worker effect, which puts this population at
a lower risk of cancer compared to the general population.
Kleinman et al. [2015] investigated cancer incidence in 39,946
police officers employed by the New York City Police Department (NYPD)
on September 11, 2001 (6,366 women), followed during the time periods
1995 to 2000 and 2002 to 2014. The authors reported a 44 percent
increase in the overall median age-adjusted incidence rate for all
cancers, but no increase in the overall median age-adjusted incidence
rates for either malignant neoplasms of the uterus, unspecified part
(based on two cases diagnosed pre-9/11 and zero cases diagnosed post-9/
11) or uterine adenosarcomas (based on zero cases diagnosed pre-9/11
and three cases post-9/11). This study is limited by the inherent
problems with its design (i.e., the effects of age, time period, and
cohort parameters are intertwined in a manner which complicates study
interpretation); the study is further limited by the small number of
cancer cases observed as well as the absence of information regarding
participants' presence in the dust cloud and the dates and duration of
their 9/11 exposures.
Stein et al. [2016] conducted a mortality study of 28,918 rescue/
recovery workers (4,286 women) enrolled in the WTC Health Program
between July 16, 2002, and December 31, 2011. The authors were aware
that 16,177 WTC responders were alive due to follow-up visits after the
end of 2011, and therefore linked the remainder (n = 12,741) to the
National Death Index (NDI). Mortality information from the NDI was
supplemented by next-of-kin report. Similar to the study by Solan et
al. [2013], discussed above, the authors of this study created an
integrated exposure variable using a 4-point scale (very high, high,
intermediate, and low) based on total time spent working at Ground
Zero, exposure to the dust cloud, and work on the debris pile. SMRs
were standardized for age (5-year groups), sex, race, and calendar year
to compare all-cause and cause-specific mortality among responders with
mortality in the U.S. general population. Hazard ratios were adjusted
for age on September 11, 2001, pre-September 11, 2001 occupation, sex,
race/ethnicity, year of WTC Health Program enrollment, smoking, and
measured body mass index. Overall mortality in this cohort was
statistically significantly decreased (SMR = 0.43; 95% CI, 0.39-0.48),
although an overall cancer SMR was not reported. Most cancer site-
specific SMRs were significantly decreased; however, the SMR for cancer
of the female genital organs was decreased but was not statistically
significant (SMR = 0.65, 95% CI 0.08-2.37) and was based on only two
deaths. An SMR for uterine cancer was not provided, neither were hazard
ratios for the association between WTC-related exposure variables and
mortality from
[[Page 49959]]
uterine cancer. Some potential confounders, such as family cancer
history, were not measured. The study is prone to selection bias
because enrollment in the WTC Health Program was voluntary. Social
Security numbers were available for only 37 percent of the records sent
to NDI for linkage, limiting the quality of the matches. The healthy
worker effect may put this population at a lower risk of cancer
compared to the general population.
Quantity and Quality Review of Relevant Studies
The quantity and quality of these seven studies were reviewed
together to examine whether the available evidence has the potential to
provide a basis for a decision on whether to add uterine cancer,
including endometrial cancer, to the List. Prospective cohort studies,
like those described above, have the advantage that study participants
are considered to be disease-free at the beginning of the observation
period when their exposure occurred; therefore, in such studies it is
often possible to establish the temporal sequence between exposure and
outcome. Cancer studies, however, present unique concerns since some
cancers become apparent only after long periods of time following
exposure.\31\ This latency effect means it is possible that a cancer
may have been present but undetected prior to September 11, 2001. In
addition, all of the studies described above have had a relatively
short period of follow-up since September 11, 2001.
---------------------------------------------------------------------------
\31\ This delay between environmental exposure and onset of
cancer symptoms is referred to as the ``cancer latency period.'' For
more information about latency for cancers and how the WTC Health
Program has addressed this issue, please see Minimum Latency & Types
or Categories of Cancer, Jan. 6, 2015, https://www.cdc.gov/wtc/pdfs/policies/WTCHP-Minimum-Cancer-Latency-PP-01062015-508.pdf.
---------------------------------------------------------------------------
The size and makeup of the cohorts studied may also limit the
usefulness of the studies. The studies discussed above may not have the
necessary statistical power to detect excesses in uterine cancer, due
to the small number of females in the cohort. This is especially a
concern with studies of 9/11-exposed rescue/recovery workers since
those cohorts are not sizeable and only approximately 15 percent
female. Moreover, the overlap in participation in the studies may limit
the interpretation of consistency of findings among the studies.
Approximately 20 percent of 9/11-exposed rescue/recovery workers
enrolled in the WTC Health Program are also enrolled in the WTC Health
Registry. These two cohorts also may be prone to selection bias,
because enrollment in the respective programs was voluntary. For the
WTC Health Registry cohort, it is possible that differential
participation due to race/ethnicity, socioeconomic status, age, or
their perception of being affected by the 9/11 attacks, may have
occurred. For the rescue/recovery worker cohort enrolled in the WTC
Health Program, their health status, including their cancer diagnosis,
may have prompted them to enroll. A strength of these studies is that
findings are available for both 9/11-exposed rescue/recovery workers as
well as survivors.
The relevant studies published to date, and reviewed above, do not
provide consistent evidence that uterine cancer, including endometrial
cancer, incidence or mortality is elevated among WTC responders and/or
survivors. In addition, the studies did not report a dose-response
relationship between WTC-related exposures and uterine cancer,
including endometrial cancer. Taken together, these studies do not have
sufficient quality and quantity to demonstrate a potential to provide a
basis for a decision on whether to add uterine cancer, including
endometrial cancer, to the List. Accordingly, these studies are not
further reviewed.
Administrator Determination
Upon review of the evidence available in peer-reviewed, published,
epidemiological studies and updates regarding uterine cancer, including
endometrial cancer, among 9/11-exposed populations, the Administrator
has determined that the available evidence does not have the potential
to provide a basis for deciding whether to propose adding uterine
cancer, including endometrial cancer, to the List. Accordingly, the
Administrator has not directed the Program to assess the available
evidence using Methods 1, 2, or 3, nor has he directed the Program to
request advice from the STAC pursuant to Method 4, discussed above.
The WTC Health Program may consider uterine cancer, including
endometrial cancer, to be a condition medically associated with a
certified WTC-related health condition in individual cases. Program
members who think their uterine or endometrial cancer is a side effect
of treatment of a certified WTC-related health condition should ask
their WTC Health Program medical provider whether their endometrial
cancer might be considered a medically associated health condition.
E. Administrator's Final Decision on Whether To Propose the Addition of
Uterine Cancer, Including Endometrial Cancer, to the List
Pursuant to PHS Act, sec. 3312(a)(6)(B)(iv) and 42 CFR
88.16(a)(2)(iv), the Administrator has determined that insufficient
evidence is available to take further action at this time, including
proposing the addition of uterine cancer, including endometrial cancer,
to the List (pursuant to PHS Act, sec. 3312(a)(6)(B)(ii) and 42 CFR
88.16(a)(2)(ii)) or publishing a determination not to publish a
proposed rule in the Federal Register (pursuant to PHS Act, sec.
3312(a)(6)(B)(iii) and 42 CFR 88.16(a)(2)(iii)). The Administrator has
also determined that requesting a recommendation from the STAC
(pursuant to PHS Act, sec. 3312(a)(6)(B)(i) and 42 CFR 88.16(a)(2)(i))
is unwarranted.
For the reasons discussed above, the Petition 023 request to add
endometrial cancer to the List of WTC-Related Health Conditions is
denied.
F. Approval To Submit Document to the Office of the Federal Register
The Secretary, HHS, or his designee, the Director, Centers for
Disease Control and Prevention (CDC) and Administrator, Agency for
Toxic Substances and Disease Registry (ATSDR), authorized the
undersigned, the Administrator of the WTC Health Program, to sign and
submit the document to the Office of the Federal Register for
publication as an official document of the WTC Health Program. Robert
Redfield M.D., Director, CDC, and Administrator, ATSDR, approved this
document for publication on September 12, 2019.
John J. Howard,
Administrator, World Trade Center Health Program and Director, National
Institute for Occupational Safety and Health, Centers for Disease
Control and Prevention, Department of Health and Human Services.
[FR Doc. 2019-20364 Filed 9-23-19; 8:45 am]
BILLING CODE 4163-18-P