[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]


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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.

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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).
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    \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.
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    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\
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    \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, http://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.
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    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.
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    \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.
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    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\),
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    \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.
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    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
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    \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.
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    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\
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    \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.
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    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.
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    \9\ See Petition 023, WTC Health Program: Petitions Received, 
http://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.
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    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.
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    \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/index.html/.
    \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.
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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\
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    \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.
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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.
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    \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.
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    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\
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    \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.
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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.
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    \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.
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    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