Ischaemic heart and cerebrovascular disease mortality in uranium enrichment workers.

OBJECTIVE: Linear and non-linear dose-response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers. METHODS: Rate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease. RESULTS: There was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null. CONCLUSIONS: Non-linear dose-response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality.

World Trade Center Health Program: First Decade of Research.

The terrorist attacks on 11 September 2001 placed nearly a half million people at increased risk of adverse health. Health effects research began shortly after and continues today, now mostly as a coordinated effort under the federally mandated World Trade Center (WTC) Health Program (WTCHP). Established in 2011, the WTCHP provides medical monitoring and treatment of covered health conditions for responders and survivors and maintains a research program aimed to improve the care and well-being of the affected population. By 2020, funds in excess of USD 127 M had been awarded for health effects research. This review describes research findings and provides an overview of the WTCHP and its future directions. The literature was systematically searched for relevant articles published from 11 September 2001 through 30 June 2020. Synthesis was limited to broad categories of mental health, cancer, respiratory disease, vulnerable populations, and emerging conditions. In total, 944 WTC articles were published, including peer-reviewed articles funded by the WTCHP (n = 291) and other sources. Research has focused on characterizing the burden and etiology of WTC-related health conditions. As the program moves forward, translational research that directly enhances the care of individuals with chronic mental and physical health conditions is needed.

Mortality in a cohort of US firefighters from San Francisco, Chicago and Philadelphia: an update.

OBJECTIVES: To update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort. METHODS: Vital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration. RESULTS: Compared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD). CONCLUSIONS: This update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

Increased overall and cause-specific mortality associated with disability among workers' compensation claimants with low back injuries.

BACKGROUND: Mortality tends to be higher among people who do not work than among workers, but the impact of work-related disability on mortality has not been well studied. METHODS: The vital status through 2015 was ascertained for 14 219 workers with an accepted workers' compensation claim in West Virginia for a low back injury in 1998 or 1999. Mortality among the cohort compared with the West Virginia general population was assessed using standard life table techniques. Associations of mortality and disability-related factors within the cohort were evaluated using Cox proportional hazards regression. RESULTS: Compared to the general population, mortality from accidental poisoning was significantly elevated among the overall cohort and lost-time claimants. Most deaths from accidental poisoning in the cohort were due to drug overdoses involving opioids. Mortality from intentional self-harm was also significantly elevated among lost-time claimants. In internal analyses, overall mortality and mortality from cancer, heart disease, intentional self-harm, and drug overdoses involving opioids was significantly associated with lost time. Overall mortality and mortality from drug overdoses involving opioids were also significantly associated with amount of lost time, permanent partial disability, and percent permanent disability. Heart disease mortality was also significantly associated with the amount of lost time. CONCLUSIONS: The results suggest that disability itself may impact mortality risks. If confirmed, these results reinforce the importance of return to work and other efforts to reduce disability.

Dose-response relationships between internally-deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948-2011.

OBJECTIVE: To examine dose-response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers. METHODS: Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work-related medical X-rays and contaminant radionuclides technetium (99 Tc) and plutonium (239 Pu) as potential confounders. RESULTS: Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates. CONCLUSION: Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort.

Cancer mortality update with an exposure response analysis among styrene-exposed workers in the reinforced plastics boatbuilding industry.

BACKGROUND: There is sparse and inconsistent evidence of an association between styrene exposure and cancer. METHODS: This study examines mortality patterns in a previously studied cohort of 5201 workers employed in two Washington boat-building facilities, extending follow-up 5 years. Standardized mortality ratios (SMR) were calculated using state rates as referent. Cox regression calculated rate ratios (RR) per year employed in styrene-exposed exposed jobs. RESULTS: No excess deaths from lymphohematopoietic cancers (LHCs) were observed (SMR: 0.99, 95%CI: 0.74-1.30) when compared to the referent population; however, the relative risk increased with duration of employment in internal analyses. Conversely, lung cancer mortality was significantly elevated (SMR: 1.24, 95%CI: 1.08-1.41), but there was no evidence of a dose-response relationship. CONCLUSION: We found evidence that occupational exposure to styrene was associated with increased LHC risk, while no such association was observed for lung cancer.

Mortality in a combined cohort of uranium enrichment workers.

OBJECTIVE: To examine the patterns of cause-specific mortality and relationship between internal exposure to uranium and specific causes in a pooled cohort of 29,303 workers employed at three former uranium enrichment facilities in the United States with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Internal comparison of the dose-response relation between selected outcomes and estimated organ doses was evaluated using regression models. RESULTS: External comparison with the U.S. population showed significantly lower SMRs in most diseases in the pooled cohort. Internal comparison showed positive associations of absorbed organ doses with multiple myeloma, and to a lesser degree with kidney cancer. CONCLUSION: In general, these gaseous diffusion plant workers had significantly lower SMRs than the U.S. POPULATION: The internal comparison however, showed associations between internal organ doses and diseases associated with uranium exposure in previous studies. Am. J. Ind. Med. 60:96-108, 2017. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

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).

BACKGROUND: We previously reported a modest excess of cancer in World Trade Center (WTC)-exposed firefighters versus the general population. This study aimed to separate the potential carcinogenic effects of firefighting and WTC exposure by comparing to a cohort of non-WTC-exposed firefighters. METHODS: Relative rates (RRs) for all cancers combined and individual cancer subtypes from 9/11/2001 to 12/31/2009 were modeled using Poisson regression comparing 11,457 WTC-exposed firefighters to 8,220 urban non-WTC-exposed firefighters. RESULTS: Compared with non-WTC-exposed firefighters, there was no difference in the RR of all cancers combined for WTC-exposed firefighters (RR = 0.96, 95%CI: 0.83-1.12). Thyroid cancer was significantly elevated (RR = 3.82, 95%CI: 1.07-20.81) from 2001 to 2009; this was attenuated (RR = 3.43, 95%CI: 0.94-18.94) and non-significant when controlling for possible surveillance bias. Prostate cancer was elevated during the latter half (2005-2009; RR = 1.38, 95%CI: 1.01-1.88). CONCLUSIONS: Further follow-up is needed to assess the relationship between WTC exposure and cancers with longer latency periods. Am. J. Ind. Med. 59:722-730, 2016. © 2016 Wiley Periodicals, Inc.

Mortality among workers exposed to toluene diisocyanate in the US polyurethane foam industry: Update and exposure-response analyses.

BACKGROUND: Mortality among 4,545 toluene diisocyante (TDI)-exposed workers was updated through 2011. The primary outcome of interest was lung cancer. METHODS: Life table analyses, including internal analyses by exposure duration and cumulative TDI exposure, were conducted. RESULTS: Compared with the US population, all cause and all cancer mortality was increased. Lung cancer mortality was increased but was not associated with exposure duration or cumulative TDI exposure. In post hoc analyses, lung cancer mortality was associated with employment duration in finishing jobs, but not in finishing jobs involving cutting polyurethane foam. CONCLUSIONS: Dermal exposure, in contrast to inhalational exposure, to TDI is expected to be greater in finishing jobs and may play a role in the observed increase in lung cancer mortality. Limitations include the lack of smoking data, uncertainty in the exposure estimates, and exposure estimates that reflected inhalational exposure only. Am. J. Ind. Med. 59:630-643, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Internal exposure to uranium in a pooled cohort of gaseous diffusion plant workers.

Intakes and absorbed organ doses were estimated for 29 303 workers employed at three former US gaseous diffusion plants as part of a study of cause-specific mortality and cancer incidence in uranium enrichment workers. Uranium urinalysis data (>600 000 urine samples) were available for 58 % of the pooled cohort. Facility records provided uranium gravimetric and radioactivity concentration data and allowed estimation of enrichment levels of uranium to which workers may have been exposed. Urine data were generally recorded with facility department numbers, which were also available in study subjects' work histories. Bioassay data were imputed for study subjects with no recorded sample results (33 % of pooled cohort) by assigning department average urine uranium concentration. Gravimetric data were converted to 24-h uranium activity excretion using department average specific activities. Intakes and organ doses were calculated assuming chronic exposure by inhalation to a 5-µm activity median aerodynamic diameter aerosol of soluble uranium. Median intakes varied between 0.31 and 0.74 Bq d(-1) for the three facilities. Median organ doses for the three facilities varied between 0.019 and 0.051, 0.68 and 1.8, 0.078 and 0.22, 0.28 and 0.74, and 0.094 and 0.25 mGy for lung, bone surface, red bone marrow, kidneys, and liver, respectively. Estimated intakes and organ doses for study subjects with imputed bioassay data were similar in magnitude.

A study update of mortality in workers at a phosphate fertilizer production facility.

OBJECTIVE: To evaluate the mortality experience among 3,199 workers employed 1951-1976 at a phosphate fertilizer production plant in central Florida with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Lung cancer and leukemia risks were further analyzed using conditional logistic regression. RESULTS: The mortality due to all-causes (SMR = 1.07, 95% confidence interval [CI] 1.02-1.13, observed deaths [n] = 1,473), all-cancers (SMR = 1.16, 95%CI 1.06-1.28, n = 431), and a priori outcomes of interests including lung cancer (SMR = 1.32, 95%CI = 1.13-1.53, n = 168) and leukemia (SMR = 1.74, 95%CI = 1.11-2.62, n = 23) were statistically significantly elevated. Regression modeling on employment duration or estimated radiation scores did not show exposure-response relation with lung cancer or leukemia mortality. CONCLUSION: SMR results showed increased lung cancer and leukemia mortality in a full cohort of the phosphate fertilizer production facility. There was, however, no exposure-response relation observed among cases and matched controls.

Exposure-response relationships for select cancer and non-cancer health outcomes in a cohort of U.S. firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

OBJECTIVES: To examine exposure-response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters. METHODS: Eight cancer and four non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period. RESULTS: Among 19,309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening. CONCLUSIONS: Lung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort.

Mortality among a cohort of U.S. commercial airline cockpit crew.

BACKGROUND: We evaluated mortality among 5,964 former U.S. commercial cockpit crew (pilots and flight engineers). The outcomes of a priori interest were non-chronic lymphocytic leukemia, central nervous system (CNS) cancer (including brain), and malignant melanoma. METHODS: Vital status was ascertained through 2008. Life table and Cox regression analyses were conducted. Cumulative exposure to cosmic radiation was estimated from work history data. RESULTS: Compared to the U.S. general population, mortality from all causes, all cancer, and cardiovascular diseases was decreased, but mortality from aircraft accidents was highly elevated. Mortality was elevated for malignant melanoma but not for non-chronic lymphocytic leukemia. CNS cancer mortality increased with an increase in cumulative radiation dose. CONCLUSIONS: Cockpit crew had a low all-cause, all-cancer, and cardiovascular disease mortality but elevated aircraft accident mortality. Further studies are needed to clarify the risk of CNS and other radiation-associated cancers in relation to cosmic radiation and other workplace exposures.

Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

OBJECTIVES: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. METHODS: Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. RESULTS: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. CONCLUSIONS: Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.

The Upper Midwest Health Study: gliomas and occupational exposure to chlorinated solvents.

OBJECTIVES: Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents--carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1--trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites. RESULTS: Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. CONCLUSIONS: We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.

The Upper Midwest Health Study: a case-control study of pesticide applicators and risk of glioma.

BACKGROUND: An excess incidence of brain cancer in farmers has been noted in several studies. The National Institute for Occupational Safety and Health developed the Upper Midwest Health Study (UMHS) as a case-control study of intracranial gliomas and pesticide uses among rural residents. Previous studies of UMHS participants, using "ever-never" exposure to farm pesticides and analyzing men and women separately, found no positive association of farm pesticide exposure and glioma risks. The primary objective was to determine if quantitatively estimated exposure of pesticide applicators was associated with an increased risk of glioma in male and female participants. METHODS: The study included 798 histologically confirmed primary intracranial glioma cases (45 % with proxy respondents) and 1,175 population-based controls, all adult (age 18-80) non-metropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. The analyses used quantitatively estimated exposure from questionnaire responses evaluated by an experienced industrial hygienist with 25 years of work on farm pesticide analyses. Odds ratios (ORs) and 95 % confidence intervals (CIs) using unconditional logistic regression modeling were calculated adjusting for frequency-matching variables (10-year age group and sex), and for age and education (a surrogate for socioeconomic status). Analyses were separately conducted with or without proxy respondents. RESULTS: No significant positive associations with glioma were observed with cumulative years or estimated lifetime cumulative exposure of farm pesticide use. There was, a significant inverse association for phenoxy pesticide used on the farm (OR 0.96 per 10 g-years of cumulative exposure, CI 0.93-0.99). No significant findings were observed when proxy respondents were excluded. Non-farm occupational applicators of any pesticide had decreased glioma risk: OR 0.72, CI 0.52-0.99. Similarly, house and garden pesticide applicators had a decreased risk of glioma: OR 0.79, CI 0.66-0.93, with statistically significant inverse associations for use of 2,4-D, arsenates, organophosphates, and phenoxys. CONCLUSIONS: These results are consistent with our previous findings for UMHS of reported farm pesticide exposure and support a lack of positive association between pesticides and glioma.

Mortality of US pentachlorophenol production workers through 2005.

A cohort of 2122 US pentachlorophenol (PCP) production workers from four plants in the National Institute for Occupational Safety and Health Dioxin Registry was exposed to PCP and to polychlorinated dibenzo-p-dioxin and dibenzofuran contaminants of PCP production. A subcohort of 720 was also exposed to 2,3,7,8-tetrachlorodibenzodioxin, a contaminant of trichlorophenol (TCP) while using TCP or a TCP derivative. PCP and several production contaminants have been implicated as animal carcinogens. A priori hypotheses were that the cohort would have elevated standardized mortality ratios (SMRs) for aplastic anemia, soft-tissue sarcoma, and non-Hodgkin lymphoma, as suggested by human studies, and for leukemia and liver, adrenal, thyroid, and parathyroid cancer, as suggested by animal studies. From 1940 to 2005 1165 deaths occurred with an overall SMR of 1.01 [95% confidence limits (CI), 0.95-1.07]. Overall cancer mortality (326 deaths, SMR 1.17, CI 1.05-1.31) was in statistically significant excess. There were excess deaths for trachea, bronchus and lung cancers (126 deaths, SMR 1.36, CI 1.13-1.62), non-Hodgkin lymphoma (17 deaths, SMR 1.77, CI 1.03-2.84), chronic obstructive pulmonary disease (63 deaths, SMR 1.38, CI 1.06-1.77), and medical complications (5 deaths, SMR 3.52, CI 1.14-8.22). In race- and sex-specific analyses, white males had increased non-Hodgkin lymphoma mortality (17 deaths, SMR 1.98, CI 1.15-3.17) and males of other races had increased leukemia mortality (four deaths, SMR 4.57, CI 1.25-11.7). The excess of cancers of a priori interest, non-Hodgkin lymphoma and leukemia, provide some support for the carcinogenicity of PCP, however, further studies with more detailed exposure assessment are needed.

A nested case-control study of multiple myeloma risk and uranium exposure among workers at the Oak Ridge Gaseous Diffusion Plant.

The primary risk factors of multiple myeloma are age, race and sex, but several studies have found an association between radiological hazards and multiple myeloma. The purpose of this nested case-control study was to investigate whether workers with chronic low-level exposure to internally deposited uranium at the Oak Ridge Gaseous Diffusion Plant in eastern Tennessee were at higher risk of dying of multiple myeloma than those without occupational exposure to uranium, with the consideration of potential confounders of external ionizing radiation and occupational chemical hazards such as mercury, nickel and trichloroethylene. The main analyses were carried out using conditional logistic regression on 98 cases and 490 controls (five controls matched to each case on gender, race and age at risk). Our study showed a weak association between internal uranium dose estimated from urinalysis results and multiple myeloma risk: OR = 1.04 (95% CI 1.00-1.09) at 10 microGy with the inclusion of other risk factors. The parameter estimates and the corresponding odds ratios were very similar when internal doses were imputed for subjects without urine samples. Further studies that include updating this cohort and combining with workers from other gaseous diffusion plants are needed to investigate the relationship between multiple myeloma risk and radiation or other chemical exposures.

A nested case-control study of lung cancer risk and ionizing radiation exposure at the portsmouth naval shipyard.

Results have been inconsistent between studies of lung cancer risk and ionizing radiation exposures among workers at the Portsmouth Naval Shipyard (PNS). The purpose of this nested case-control study was to evaluate the relationship between lung cancer risk and external ionizing radiation exposure while adjusting for potential confounders that included gender, radiation monitoring status, smoking habit surrogates (socioeconomic status and birth cohort), welding fumes and asbestos. By incidence density sampling, we age-matched 3,291 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992 with 1,097 lung cancer deaths from among the same cohort. Analyses using conditional logistic regression were conducted in various model forms: log-linear (main), linear excess relative risk (ERR), and categorical. Lung cancer risk was positively associated with occupational dose (OR = 1.02 at 10 mSv; 95% CI 0.99- 1.04) but flattened after the inclusion of work-related medical X-ray doses (OR = 1.00; 95% CI 0.98-1.03) in multivariate analyses. Similar risk estimates were observed in the linear ERR model at 10 mSv of cumulative exposure with a 15-year lag.