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This study revised the thyroid doses for 2582 Ukrainian in utero cohort members exposed to Chornobyl fallout (the Ukrainian in utero cohort) based on revision of: (i) 131I thyroid activity measured in the Ukrainian population, (ii) thyroid dosimetry system for entire Ukraine, and (iii) 131I ground deposition densities in Ukraine. Other major improvements included: (i) assessment of uncertainties in the thyroid doses considering shared and unshared error, and (ii) accounting for intake of short-lived radioisotopes of tellurium and iodine (132Te+132I and 133I). Intake of 131I was the major pathway for thyroid exposure, its median contribution to the thyroid dose was 97.4%. The mean prenatal and postnatal thyroid dose from 131I was 87 mGy (median = 17 mGy), higher than previous deterministic dose of 72 mGy (median = 12 mGy). For 39 individuals (1.5%) the dose exceeded 1.0 Gy, while the highest dose among the cohort members was 2.7 Gy. The geometric standard deviation (GSD) of 1000 individual stochastic doses varied from 1.9 to 5.2 with a mean of 3.1 and a median of 3.2. The lowest uncertainty (mean GSD = 2.3, median GSD = 2.2) was found for the subjects whose mothers were measured for 131I thyroid activity, while for individuals, whose mothers were not measured, the mean and median GSDs were 3.4. Uncertainties in thyroid doses were driven by shared errors associated with the parameters of the ecological model.

A large excess risk of thyroid cancer was observed among Belarusian/Russian/Baltic Chornobyl cleanup workers. A more recent study of Ukraine cleanup workers found more modest excess risks of thyroid cancer. Dose errors in this data are substantial, associated with model uncertainties and questionnaire response. Regression calibration is often used for dose-error adjustment, but may not adequately account for the full error distribution. We aimed to examine the impact of exposure-assessment uncertainties on thyroid cancer among Ukrainian cleanup workers using Monte Carlo maximum likelihood, and compare with results derived using regression calibration. Analyses assessed the sensitivity of results to various components of internal and external dose. Regression calibration yielded an excess odds ratio per Gy (EOR/Gy) of 0.437 (95% CI - 0.042, 1.577, p = 0.100), compared with the EOR/Gy using Monte Carlo maximum likelihood of 0.517 (95% CI - 0.039, 2.035, p = 0.093). Trend risk estimates for follicular morphology tumors exhibited much more extreme effects of full-likelihood adjustment, the EOR/Gy using regression calibration of 3.224 (95% CI - 0.082, 30.615, p = 0.068) becoming ~ 50% larger, 4.708 (95% CI - 0.075, 85.143, p = 0.066) when using Monte Carlo maximum likelihood. Results were sensitive to omission of external components of dose. In summary, use of Monte Carlo maximum likelihood adjustment for dose error led to increases in trend risks, particularly for follicular morphology thyroid cancers, where risks increased by ~ 50%, and were borderline significant. The unexpected finding for follicular tumors needs to be replicated in other exposed groups.

Although NSAIDs have been associated with both reduced and increased cutaneous melanoma risk, few studies have examined these associations by ultraviolet radiation (UVR) or personal sun-sensitivity. We examined the associations between NSAID use and first primary invasive cutaneous melanoma among 58,227 non-Hispanic white participants in the United States Radiologic Technologists cohort study. Poisson regression was used to calculate rate ratios (RR) and 95% likelihood-based confidence intervals (CI), adjusting for attained age, birth cohort, and ambient UVR. No significant association of melanoma was observed for any use of NSAIDs (RR, 0.87; 95% CI, 0.71–1.09). The relative risks of melanoma for the highest categories of aspirin and other NSAID use (≥5 times per month vs. none) were 0.93 (95% CI, 0.74–1.16) and 1.02 (95% CI, 0.83–1.25), respectively. Further analyses did not reveal dose–response for trends in frequency of NSAID use or interactions with sex, UVR, eye and hair color, and skin complexion. In this large nationwide study, NSAID use was not associated with melanoma risk. Prevention Relevance: NSAIDs have been associated with both reduced and increased melanoma risk. However, few studies have examined the role of UVR or personal sun-sensitivity on these associations. Our findings strengthen the evidence that NSAID use is not associated with melanoma risk, even in sun-sensitive subgroups.

Background Recent studies have suggested that Kaposi sarcoma (KS) rates might be increasing in some racial/ethnic groups, age groups, and US regions. We estimated recent US trends in KS incidence among people living with human immunodeficiency virus (HIV; PLWH). Methods Incident KS patients aged 20–59 years were obtained from 36 cancer registries and assumed to be living with HIV. The number of PLWH was obtained from national HIV surveillance data from 2008 to 2016. Age-standardized KS rates and annual percent changes (APCs) in rates were estimated by age, sex, race/ethnicity, state, and region. Results Between 2008 and 2016, the age-adjusted KS rate among PLWH was 116/100 000. Rates were higher among males, in younger age groups, and among white PLWH. Washington, Maine, and California had the highest KS rates among PLWH. KS rates among PLWH decreased significantly (average APC = −3.2% per year, P Conclusions KS incidence rates among PLWH have decreased nationally between 2008 and 2016. Though there were no statistically significant increases in KS rates in any demographic or geographic group, nondecreasing/stagnant KS trends in some states and among younger and black PLWH highlight the need for early diagnosis and treatment of HIV infection.

ObjectivesTo evaluate cumulative occupational radiation dose response and haematopoietic malignancy mortality risks in the US radiologic technologist cohort.MethodsAmong 110 297 radiologic technologists (83 655 women, 26 642 men) who completed a baseline questionnaire sometime during 1983–1998, a retrospective cohort study was undertaken to assess cumulative, low-to-moderate occupational radiation dose and haematopoietic malignancy mortality risks during 1983–2012. Cumulative bone marrow dose (mean 8.5 mGy, range 0–430 mGy) was estimated based on 921 134 badge monitoring measurements during 1960–1997, work histories and historical data; 35.4% of estimated doses were based on badge measurements. Poisson regression was used to estimate excess relative risk of haematopoietic cancers per 100 milligray (ERR/100 mGy) bone-marrow absorbed dose, adjusting for attained age, sex and birth year.ResultsDeaths from baseline questionnaire completion through 2012 included 133 myeloid neoplasms, 381 lymphoid neoplasms and 155 leukaemias excluding chronic lymphocytic leukaemia (CLL). Based on a linear dose-response, no significant ERR/100 mGy occurred for acute myeloid leukaemia (ERR=0.0002, 95% CI 0.5, 85 cases) or leukaemia excluding CLL (ERR=0.05, 95% CI 0.5, 112 cases). Findings did not differ significantly by demographic factors, smoking or specific radiological procedures performed.ConclusionAfter follow-up averaging 22 years, there was little evidence of a relationship between occupational radiation exposure and myeloid or lymphoid haematopoietic neoplasms.

Thyroid doses were estimated for 607 subjects of the case-control study of thyroid cancer nested in the cohort of 150,813 male Ukrainian cleanup workers, who were exposed to radiation as a result of the 1986 Chernobyl nuclear power plant accident. Individual thyroid doses due to external irradiation, inhalation of (131)I and short-lived radioiodine and radiotellurium isotopes ((132)I, (133)I, (135)I, (131m)Te and (132)Te) during the cleanup mission, and intake of (131)I during residence in contaminated settlements were calculated for all study subjects, along with associated uncertainty distributions. The average thyroid dose due to all exposure pathways combined was estimated to be 199 mGy (median dose of 47 mGy; range: 0.15 mGy to 9.0 Gy), with averages of 140 mGy (median of 20 mGy; range: 0.015 mGy to 3.6 Gy) from external irradiation during the cleanup mission, 44 mGy (median of 12 mGy; range: ~0 mGy to 1.7 Gy) due to (131)I inhalation, 42 mGy (median of 7.3 mGy; range: 0.001 mGy to 3.4 Gy) due to (131)I intake during residence, and 11 mGy (median of 1.6 mGy; range: ~0 mGy to 0.38 Gy) due to inhalation of short-lived radionuclides. Internal exposure of the thyroid gland to (131)I contributed more than 50% of the total thyroid dose in 45% of the study subjects. The uncertainties of the individual stochastic doses were characterized by a mean GSD of 2.0, 1.8, 2.0 and 2.6 for external irradiation, inhalation of (131)I, inhalation of short-lived radionuclides and residential exposure, respectively. The models used for dose calculations were validated against instrumental measurements done shortly after the accident. Results of the validation showed that thyroid doses could be estimated retrospectively for Chernobyl cleanup workers two-three decades after the accident with a reasonable degree of reliability.

STUDY QUESTION Are reproductive factors and exogenous hormone use associated with incidence of cutaneous melanoma while accounting for ultraviolet radiation (UVR) exposure across different life periods and sun sensitivity factors? SUMMARY ANSWER Earlier age at menarche and late age at first birth, but not other estrogen-related factors were associated with an increased incidence rate of melanoma, with higher risks observed for earlier age at menarche and light hair color at age 15 years. WHAT IS KNOWN ALREADY Although estrogens have been recognized as photosensitizing, previous studies have reported inconsistent findings for the association of melanoma with estrogen-related factors. Most have not collected detailed skin cancer risk factors and have not thoroughly investigated effect modification by ambient UVR and sun sensitivity. STUDY DESIGN, SIZE, DURATION Participants in the US Radiologic Technologists study, an occupational cohort of 146 022 radiologic technologists (73% women), were included and followed during the four time periods (1983–1989, 1994–1998, 2003–2005 and 2012–2014). PARTICIPANTS/MATERIALS, SETTING, METHODS Non-Hispanic white female participants who completed both the second (baseline) and third questionnaires, and did not report having cancer (except keratinocyte carcinoma) at baseline, were included and followed from their age at completion of the second (baseline) questionnaire until the earlier of first primary cancer diagnosis, including invasive melanoma of the skin, or completion of either the third or fourth questionnaire. Reproductive and exogenous hormonal factors were ascertained from the second (baseline) questionnaire, which also collected information on demographic, lifestyle factors and sun sensitivity factors. Ambient UVR was assigned by linking geocoded residential locations, based on self-reported residential history information collected from the third questionnaire to satellite-based ambient UVR data from the National Aeronautics and Space Administration’s Total Ozone Mapping Spectrometer database. To examine the association of reproductive factors, exogenous hormone use, and first primary invasive melanoma of the skin, we used Poisson regression to calculate rate ratios (RRs) and 95% likelihood-based CIs, adjusting for attained age, birth cohort, lifetime average annual ambient UVR, contraceptives and menopausal hormone therapy use. To address the effect modification of ambient UVR exposure and sun sensitivities on melanoma risk, we conducted likelihood-ratio tests for multiplicative interaction. MAIN RESULTS AND THE ROLE OF CHANCE Over a median follow-up time of 17.1 years, 0.95% of eligible participants had an incident first primary melanoma (n = 444). Higher melanoma incidence rates were observed in participants with older attained age, blue/green/gray eye color, blonde/red/auburn natural hair color at age 15, fair skin complexion, and higher UVR. We found an increased incidence rate of melanoma in women who experienced menarche at an earlier age (13, 12 and LIMITATIONS, REASONS FOR CAUTION Information on reproductive history and exogenous hormone use was self-reported. We did not have information on specific doses or formulations of exogenous hormone medications or breastfeeding. WIDER IMPLICATIONS OF THE FINDINGS Women residing in areas of high ambient UVR and those with blonde/red/auburn natural hair color may constitute an additional high-risk group in need of more frequent skin cancer screening. Identifying susceptible periods of exposure or factors that modify UVR susceptibility may aid in guiding more targeted guidelines for melanoma prevention. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Background While there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume. Methods To assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined. Results The analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P P P Conclusions This is the first study to examine the association between 131I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given that this effect was observed at very low doses and was restricted to a narrow dose range, further studies are necessary to better understand the effect.

Background Basal cell carcinoma of the skin (BCC) is the most common cancer in populations of European ancestry. Although consistently linked with basal cell carcinoma of the skin in case-control studies, few prospective cohort studies have evaluated the shape of the exposure-response of basal cell carcinoma associated with cumulative radiant solar ultraviolet exposure (UVR). Methods We followed 63,912 white cancer-free US radiologic technologists from entry (1983–1998) to exit (2003–2005) with known ultraviolet irradiance at up to 5 residential locations. Using generalized-additive and relative risk models we analyzed the exposure-response of basal cell carcinomas associated with ambient cumulative ultraviolet radiant exposure using ground-based National Solar Radiation database Average Daily Total Global data and satellite-based National Aeronautics and Space Administration Total Ozone Mapping Spectrometer data. Results There were 2151 technologists with an incident primary basal cell carcinoma. Risk of basal cell carcinoma rose with increasing cumulative ultraviolet radiation exposure using both measures, such that 1 MJ cm− 2 increased basal cell carcinoma risk by 8.48 (95% CI 5.22, 11.09, p p Conclusions We observed increases in risk of basal cell carcinoma and a similar exposure-response for ground-based and satellite ultraviolet radiation measures. Our observations suggest that interventions should concentrate on persons with higher levels of ultraviolet radiation exposure.

BACKGROUND: Ionizing radiation is a known cause of female breast cancer, but there have been few studies of the risk after prolonged radiation exposure at low dose rates. METHODS: This population-based case-control study estimated breast cancer risk after ∼25 years’ exposure to radiation from the Chernobyl accident. Cases (n = 468) were women ≤55 years old when first diagnosed with invasive breast cancer during October 2008 through February 2013, who lived in Bryansk Oblast, Russia at the time of the accident and their diagnoses. Controls, individually matched to cases on birth year, administrative district of residence and urban vs non-urban settlement during the accident, were women without breast cancer who lived in Bryansk Oblast at the time of the accident and on their cases’ diagnosis dates (n = 468). Subjects were interviewed regarding residence, dietary and food source histories to support individualized estimation of their radiation doses to the breast, which ranged from 0.04 − 41 centigray (cGy) (mean 1.3 cGy). RESULTS: In multivariable analyses, the odds ratio for breast cancer risk was 3.0 [95% confidence interval (CI): 1.3, 7.0] and 2.7 (95% CI: 1.0, 7.3) in the seventh and eighth dose octiles, respectively, relative to the lowest octile. Analyses of dose effect modification suggested that radiation-related risk may have been higher in women who were younger at the time of the accident and/or at the time of diagnosis. CONCLUSIONS: This study suggests that prolonged exposure to ionizing radiation at low dose rates can increase risk of breast cancer.

Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261,500 transplant recipients in the United States. Two-hundred thirty-one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2.01, 95%CI 1.44–2.82), transplanted organ (0.33, 0.20–0.57, for liver transplants and 3.07, 1.96–4.81, for lung transplants, compared with kidney transplants), and racial/ethnic groups other than non-Hispanic whites (0.09, 0.04–0.20). In addition, incidence increased with age and during the first three years following transplant, and was higher in recipients prescribed cyclosporine/azathioprine maintenance therapy (aIRR 1.79, 95%CI 1.09–2.93, compared with use of tacrolimus/mycophenolate mofetil) and following a diagnosis of cutaneous squamous cell carcinoma (4.21, 2.69–0.94). The elevation in lip cancer incidence is consistent with an effect of immunosuppression. Notably, the very strong associations with white race and history of prior skin cancer point to an important role for ultraviolet radiation exposure, and cyclosporine and azathioprine may contribute as photosensitizing or DNA damaging agents.

Background Pregnancy and lactation may constitute radiation-sensitive reproductive periods due to rapid cell proliferation and concentration of radioiodine in the lactating breast. However, there are limited epidemiological data among women exposed to radiation during these periods. Methods We examined incidence of breast cancer in a cohort of 3214 women who were pregnant and/or lactating within 2 months (26 April to 30 June 1986) of the Chernobyl accident and residing in contaminated regions of Belarus. There were 33 breast cancers identified through linkage with the Belarusian National Cancer Registry. Breast cancer rates among women who were either pregnant and/or lactating were compared with population rates by calculating standardized incidence ratios (SIR) and 95% confidence intervals (CI) adjusting for attained age, oblast, urban/rural residence and calendar year. Results Among women who were lactating, we found a greater than 2-fold increased risk of breast cancer compared with the general population, SIR = 2.49 (95% CI: 1.55, 3.75). In contrast, women who were pregnant were not at increased risk (SIR = 0.84 95% CI: 0.46, 1.38). The SIR was highest in women who were exposed at a younger age and at the earliest time period since the accident, though stratified analyses had limited sample sizes. Conclusions We found a significantly increased risk of breast cancer among women residing in contaminated areas of Belarus who were lactating at the time of the accident and may have had elevated exposure to radioiodine, when compared with the general population. Studies of breast cancer with individual radiation dose estimates among women exposed during lactation are warranted.

Although much is known about the radiation-related risk of thyroid cancer in those exposed at young ages, less is known about the risk due to adult exposure, particularly in men. We aimed to examine the association between thyroid radiation dose received during adulthood and thyroid cancer risk in men. We conducted a nested case-control study (149 cases; 458 controls) of male, Ukrainian cleanup workers who first worked in the Chornobyl zone between ages 18 and 59 years, with cases identified through linkage with the National Cancer Registry of Ukraine from 1988 to 2012. Individual thyroid doses due to external and internal exposure during the cleanup mission and during residence in contaminated settlements were estimated (total dose mean 199 mGy; range 0.15 mGy to 9.0 Gy). The excess odds ratio per gray (EOR/Gy) for overall thyroid cancer was 0.40 (95% CI: - 0.05, 1.48; p-value = 0.118). Time since exposure was borderline significant (p-value = 0.061) in modifying this association so that less time since exposure was associated with a stronger EOR/Gy. An elevated, but nonsignificant association was observed for follicular thyroid cancer (EOR/Gy = 1.72; 95% CI: - 0.25, 13.69; p-value = 0.155) based on a small number of cases (n = 24). Our findings for radiation-related overall thyroid cancer risk are consistent with evidence of increased risks observed in most of the other studies of adult exposure, though the magnitude of the effect in this study is lower than in the previous case-control study of Chornobyl cleanup workers.

Radiation doses of parents exposed from the Chornobyl accident as cleanup workers or evacuees were estimated in the National Cancer Institute-National Research Center for Radiation Medicine trio (i.e. father, mother, offspring) study aimed at investigating the radiation effects on germline de novo mutations in children as well as other outcomes. Paternal (testes) and maternal (ovaries) gonadal doses were calculated along with associated uncertainty distributions for the following exposure pathways: (a) external irradiation during the cleanup mission, (b) external irradiation during residence in Pripyat, and (c) external irradiation and (d) ingestion of radiocesium isotopes, such as 134Cs and 137Cs, during residence in settlements other than Pripyat. Gonadal doses were reconstructed for 298 trios for the periods from the time of the accident on 26 April 1986 to two time points before the child’s date of birth (DOB): 51 (DOB-51) and 38 (DOB-38) weeks. The two doses, DOB-51 and DOB-38 were equal (within 1 mGy) in most instances, except for 35 fathers where the conception of the child occurred within 3 months of exposure or during exposure. The arithmetic mean of gonadal DOB-38 doses was 227 mGy (median: 11 mGy, range 0–4080 mGy) and 8.5 mGy (median: 1.0 mGy, range 0–550 mGy) for fathers and mothers, respectively. Gonadal doses varied considerably depending on the exposure pathway, the highest gonadal DOB-38 doses being received during the cleanup mission (mean doses of 376 and 34 mGy, median of 144 and 7.4 mGy for fathers and mothers, respectively), followed by exposure during residence in Pripyat (7.7 and 13 mGy for mean, 7.2 and 6.2 mGy for median doses) and during residence in other settlements (2.0 and 2.1 mGy for mean, 0.91 and 0.81 mGy for median doses). Monte Carlo simulations were used to estimate the parental gonadal doses and associated uncertainties. The geometric standard deviations (GSDs) in the individual parental stochastic doses due to external irradiation during the cleanup mission varied from 1.2 to 4.7 (mean of 1.8), while during residence in Pripyat they varied from 1.4 to 2.8 (mean of 1.8), while the mean GSD in doses received during residence in settlements other than Pripyat was 1.3 and 1.4 for external irradiation and ingestion of radiocesium isotopes, respectively.

Background: Cutaneous basal cell carcinoma (BCC) has long been associated with UV radiation (UVR) exposure, but data are limited on risks by anatomic site. Methods: We followed 63,912 cancer-free White U.S. radiologic technologists from cohort entry (1983–1989/1994–1998) to exit (date first BCC via 2003–2005 questionnaire). We estimated associations between cumulative ambient UVR and relative/absolute risks of self-reported BCC by anatomic location via Poisson models. Results: For incident first primary BCC in 2,124 subjects (mean follow-up, 16.9 years) log[excess relative risks] (ERR) of BCC per unit cumulative ambient UVR = 1.27/MJ cm–2 [95% confidence interval (CI): 0.86–1.68; Ptrend < 0.001] did not vary by anatomic site (P = 0.153). However, excess absolute risks of BCC per unit cumulative ambient UVR were large for the head/neck = 5.46/MJ cm–2/104 person-year (95% CI: 2.92–7.36; Ptrend < 0.001), smaller for the trunk (2.56; 95% CI: 1.26–3.33; Ptrend = 0.003), with lesser increases elsewhere. There were lower relative risks, but higher absolute risks, for those with Gaelic ancestry (P < 0.001), also higher absolute risks among those with fair complexion, but relative and absolute risks were not generally modified by other constitutional, lifestyle or medical factors for any anatomic sites. Excess absolute and relative risk was concentrated 5–15 years before time of follow-up. Conclusions: BCC relative and absolute risk rose with increasing cumulative ambient UVR exposure, with absolute risk highest for the head/neck, to a lesser extent in the trunk. Impact: These associations should be evaluated in other White and other racial/ethnic populations along with assessment of possible modification by time outdoors, protective, and behavioral factors.

Genomics of radiation-induced damage The potential adverse effects of exposures to radioactivity from nuclear accidents can include acute consequences such as radiation sickness, as well as long-term sequelae such as increased risk of cancer. There have been a few studies examining transgenerational risks of radiation exposure but the results have been inconclusive. Morton et al. analyzed papillary thyroid tumors, normal thyroid tissue, and blood from hundreds of survivors of the Chernobyl nuclear accident and compared them against those of unexposed patients. The findings offer insight into the process of radiation-induced carcinogenesis and characteristic patterns of DNA damage associated with environmental radiation exposure. In a separate study, Yeager et al. analyzed the genomes of 130 children and parents from families in which one or both parents had experienced gonadal radiation exposure related to the Chernobyl accident and the children were conceived between 1987 and 2002. Reassuringly, the authors did not find an increase in new germline mutations in this population. Science , this issue p. eabg2538 , p. 725

IMPORTANCE: Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor characteristics are unknown. OBJECTIVE: To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021. MAIN OUTCOMES AND MEASURES: Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors. RESULTS: A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 [61.7%] male; 272 241 [61.2%] non-Hispanic White). Melanoma was the most common cancer (1471 [61.8%]), followed by Merkel cell carcinoma (334 [14.0%]), Kaposi sarcoma (186 [7.8%]), sebaceous carcinoma (170 [7.1%]), and cutaneous lymphomas (108 [4.5%]). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.

Epidemiological evidence for a radiation effect on prostate cancer risk has been inconsistent and largely indicative of no or little effect. Here we studied prostate cancer incidence among males of the Life Span Study cohort of atomic bomb survivors in a follow-up from 1958 to 2009, eleven years more than was previously reported. During this period there were 851 incident cases of prostate cancer among 41,544 male subjects, doubling the total number of cases in the cohort. More than 50% of the cases were diagnosed among those who were less than 20 years of age at the time of the bombings and who were at, or near, the ages of heightened prostate cancer risks during the last decade of follow-up. In analyses of the radiation dose response using Poisson regression methods, we used a baseline-rate model that allowed for calendar period effects corresponding to the emergence of prostate-specific antigen screening in the general population as well as effects of attained age and birth cohort. The model also allowed for markedly increased baseline rates among the Adult Health Study participants between 2005 and 2009, a period during which a prostate-specific antigen test was included in Adult Health Study biennial health examinations. We found a significant linear dose response with an estimated excess relative risk (ERR) per Gy of 0.57 (95% CI: 0.21, 1.00, P = 0.001). An estimated 40 of the observed cases were attributed to radiation exposure from the bombings. There was a suggestion of the ERR decreasing with increasing age at exposure (P = 0.09). We found no indication of effects of smoking, alcohol consumption and body mass index on the baseline risk of prostate cancer. The observed dose response strengthens the evidence of a radiation effect on the risk of prostate cancer incidence in the atomic bomb survivors.

There is limited evidence concerning the association between radiation exposure and ovarian cancer. We evaluated radiation risk of ovarian cancer between 1958 and 2009 among 62,534 female atomic bomb survivors in the Life Span Study cohort, adding 11 years of follow-up from the previously reported study. Poisson regression methods were used to estimate excess relative risk per Gy (ERR/Gy) for total ovarian cancer and according to tumor type. We assessed the modifying effect of follow-up period and other factors on the radiation risk. We ascertained 288 first primary ovarian cancers including 77 type 1 epithelial cancers, 75 type 2 epithelial cancers, 66 epithelial cancers of undetermined type and 70 other cancers. Radiation dose was positively, although not significantly, associated with risk of total ovarian cancer [ERR/Gy = 0.30, 95% confidence interval (CI): -0.22 to 1.11]. There was a suggestion of heterogeneity in radiation effects (P = 0.08) for type 1 (ERR/Gy = -0.32, 95% CI

Importance Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights. Objective To assess SC incidence and patient survival after solid organ transplantation. Design, Setting, and Participants This cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals. Main Outcomes and Measures Sebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population. Results A total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P

The Trinity nuclear test, conducted in 1945, exposed residents of New Mexico to varying degrees of radioactive fallout. Companion papers in this issue have detailed the results of a dose reconstruction that has estimated tissue-specific radiation absorbed doses to residents of New Mexico from internal and external exposure to radioactive fallout in the first year following the Trinity test when more than 90% of the lifetime dose was received. Estimated radiation doses depended on geographic location, race/ethnicity, and age at the time of the test. Here, these doses were applied to sex- and organ-specific risk coefficients (without applying a dose and dose rate effectiveness factor to extrapolate from a population with high-dose/high-dose rates to those with low-dose/low-dose rates) and combined with baseline cancer rates and published life tables to estimate and project the range of radiation-related excess cancers among 581,489 potentially exposed residents of New Mexico. The total lifetime baseline number of all solid cancers [excluding thyroid and non-melanoma skin cancer (NMSC)] was estimated to be 183,000 from 1945 to 2034. Estimates of ranges of numbers of radiation-related excess cancers and corresponding attributable fractions from 1945 to 2034 incorporate various sources of uncertainty. We estimated 90% uncertainty intervals (UIs) of excess cancer cases to be 210 to 460 for all solid cancers (except thyroid cancer and NMSC), 80 to 530 for thyroid cancer, and up to 10 for leukemia (except chronic lymphocytic leukemia), with corresponding attributable fractions ranging from 0.12% to 0.25%, 3.6% to 20%, and 0.02% to 0.31%, respectively. In the counties of Guadalupe, Lincoln, San Miguel, Socorro, and Torrance, which received the greatest fallout deposition, the 90% UI for the projected fraction of thyroid cancers attributable to radioactive fallout from the Trinity test was estimated to be from 17% to 58%. Attributable fractions for cancer types varied by race/ethnicity, but 90% UIs overlapped for all race/ethnicity groups for each cancer grouping. Thus, most cancers that have occurred or will occur among persons exposed to Trinity fallout are likely to be cancers unrelated to exposures from the Trinity nuclear test. While these ranges are based on the most detailed dose reconstruction to date and rely largely on methods previously established through scientific committee agreement, challenges inherent in the dose estimation, and assumptions relied upon both in the risk projection and incorporation of uncertainty are important limitations in quantifying the range of radiation-related excess cancer risk.

Sebaceous carcinoma is an aggressive skin cancer with a 5-year overall survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been increasing in the United States for several decades, but the underlying reasons for this increase are unclear. In this article, we review the epidemiology and genetics of sebaceous carcinoma, including recent population data and tumor genomic analyses that provide new insights into underlying tumor biology. We further discuss emerging evidence of a possible viral etiology for this cancer. Finally, we review the clinical implications of recent advances in sebaceous carcinoma research for screening, prevention, and treatment.

This population-based cohort study examines associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas in recipients of lung transplants., Key Points Question What is the association between voriconazole, an antifungal used to treat aspergillosis infections, and the risk of keratinocyte carcinomas among recipients of lung transplants? Findings In a population-based cohort study of 9599 non-Hispanic white recipients of 9793 lung transplants in the United States (2007-2016) with linkage to pharmacy claims, increasing cumulative voriconazole exposure was associated with an increased risk of cutaneous squamous cell carcinoma. Meaning These findings suggest that physicians caring for lung transplant recipients at high risk for aggressive keratinocyte carcinomas should limit voriconazole exposure when possible and encourage skin protection behaviors and more frequent cancer screenings., Importance The antifungal medication voriconazole is used to prevent and treat aspergillosis, a major cause of mortality among recipients of lung transplants (hereinafter referred to as lung recipients). Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC). Objective To examine associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas (SCC and cutaneous basal cell carcinoma [BCC]) in lung recipients. Design, Setting, and Participants This population-based cohort study included non-Hispanic white patients (n = 9599) who underwent lung transplant in the United States from January 1, 2007, to December 31, 2016, identified through the national Scientific Registry of Transplant Recipients with data linkable to pharmacy claims. Data were analyzed from March 1, 2018, to February 13, 2019. Exposures Antifungal medication use, including voriconazole, itraconazole, posaconazole, and other antifungals, was ascertained from pharmacy claims and treated as a time-varying exposure (assessed every 30 days). Cumulative antifungal exposure was calculated as the total number of exposed months. Main Outcomes and Measures Primary outcomes were the first SCC or BCC reported to the transplant registry by transplant centers. Follow-up began at transplant and ended at SCC or BCC diagnosis, transplant failure or retransplant, death, loss to follow-up, or December 31, 2016. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) for each antifungal medication. Results Among the 9793 lung transplants in 9599 recipients included in the analysis, median age at transplant was 59 (interquartile range [IQR], 48-65) years, 5824 (59.5%) were male, and 5721 (58.4%) reported ever smoking. During a median follow-up of 3.0 (IQR, 1.4-5.0) years after transplant, 1031 SCCs (incidence, 322 per 10 000 person-years) and 347 BCCs (incidence, 101 per 10 000 person-years) were reported. Compared with lung recipients with no observed voriconazole use, those with 1 to 3 months of voriconazole use experienced increased AHR for SCC of 1.09 (95% CI, 0.90-1.31); 4 to 7 months, 1.42 (95% CI, 1.16-1.73); 8 to 15 months, 2.04 (95% CI, 1.67-2.50); and more than 15 months, 3.05 (95% CI, 2.37-3.91). Ever itraconazole exposure was associated with increased SCC risk (AHR, 1.20; 95% CI, 1.00-1.45). For BCC, risk was not associated with voriconazole use but was increased with itraconazole use (AHR, 1.74; 95% CI, 1.27-2.37) or posaconazole use (AHR, 1.55; 95% CI, 1.00-2.41). Conclusions and Relevance In this study, voriconazole use was associated with increased SCC risk among lung recipients, especially after prolonged exposure. Further research evaluating the risk-benefit ratio of shorter courses or alternative medications in transplant recipients at high risk for SCC should be considered.

Thyroid radiation doses were estimated for a cohort of 2,965 Belarusian persons who were exposed in utero and during early life to fallout from the Chernobyl nuclear power plant accident. Prenatal and postnatal doses to the thyroid due to intake of iodine-131 ((131)I), external irradiation from radionuclides deposited on the ground and ingestion of cesium isotopes ((134)Cs and (137)Cs) were calculated for all cohort members. Dose estimation was based on personal interviews with subjects’ mothers which collected data on subjects’ residential history, consumption by mothers during time of pregnancy and breastfeeding, as well as consumption by subjects after birth. Direct instrumental measurement of radioactivity in mothers and the study subjects, if available, were also used for calculation of doses. Intake of (131)I by mother was found to be the predominant pathway for thyroid exposure for the study subjects. The average thyroid dose due to all exposure pathways was estimated to be 137 milli-Gray (mGy) (median dose of 25 mGy, maximal dose of 14.8 Gy), including 130 mGy (median dose of 17 mGy, maximal dose of 14.8 Gy) from (131)I intake, 4.9 mGy (median dose of 3.0 mGy, maximal dose of 102 mGy) due to external irradiation, and 2.5 mGy (median dose of 1.7 mGy, maximal dose of 47 mGy) due to ingestion of (134, 137)Cs. The dose estimates will be used to evaluate the radiation-related risk of thyroid cancer and other thyroid diseases in this unique cohort.

BACKGROUND: Children and adolescents exposed to radioactive iodine-131 (I-131) in fallout from the 1986 Chernobyl nuclear accident appear to be at increased risk of thyroid cancer and benign thyroid nodules. The prenatal period is also considered radiosensitive, and the fetal thyroid can absorb I-131 from the maternal circulation. OBJECTIVES: We aimed to estimate the risk of malignant and benign thyroid nodules in individuals exposed prenatally. METHODS: We studied a cohort of 2582 subjects in Ukraine with estimates of I-131 prenatal thyroid dose (mean = 72.6 mGy), who underwent two standardized thyroid screening examinations. To evaluate the dose-response relationship, we estimated the excess OR (EOR) using logistic regression. RESULTS: Based on a combined total of eight cases diagnosed at screenings from 2003 to 2006 and 2012 to 2015, we found a markedly elevated, albeit not statistically significant, dose-related risk of thyroid cancer (EOR/Gy = 3.91, 95% CI: –1.49, 65.66). At cycle 2 (n = 1,786), there was a strong and significant association between I-131 thyroid dose and screen-detected large benign nodules (≥10 mm) (EOR/Gy = 4.19, 95% CI: 0.68, 11.62; P = 0.009), but no significant increase in risk for small nodules (

There are well-documented associations of glaucoma with high-dose radiation exposure, but only a single study suggesting risk of glaucoma, and less conclusively macular degeneration, associated with moderate-dose exposure. We assessed risk of glaucoma and macular degeneration associated with occupational eye-lens radiation dose, using participants from the US Radiologic Technologists Study, followed from the date of surveys in 1994–1998, 2003–2005 to the earliest of diagnosis of glaucoma or macular degeneration, cancer other than non-melanoma skin cancer, or date of last survey (2012–2014). We excluded those with baseline disease or previous radiotherapy history. Cox proportional hazards models with age as timescale were used. There were 1631 cases of newly self-reported doctor-diagnosed cases of glaucoma and 1331 of macular degeneration among 69,568 and 69,969 eligible subjects, respectively. Estimated mean cumulative eye-lens absorbed dose from occupational radiation exposures was 0.058 Gy. The excess relative risk/Gy for glaucoma was −0.57 (95% CI −1.46, 0.60, p = 0.304) and for macular degeneration was 0.32 (95% CI −0.32, 1.27, p = 0.381), suggesting that there is no appreciable risk for either endpoint associated with low-dose and low dose-rate radiation exposure. Since this is the first examination of glaucoma and macular degeneration associated with low-dose radiation exposure, this result needs to be replicated in other low-dose studies.

OBJECTIVE: Childhood exposure to acute, high-dose radiation has consistently been associated with risk of benign and malignant intracranial tumors of the brain and central nervous system, but data on risks following adulthood exposure to protracted, low-to-moderate dose radiation are limited. In a large cohort of radiologic technologists, we quantified the association between protracted, low-to-moderate dose radiation and malignant intracranial tumor mortality. METHODS: The study population included 83,655 female and 26,642 male U.S. radiologic technologists who were certified for at least two years as of 1982. The cohort was followed from the completion date of the first or second survey (1983–1989 or 1994–1998) to the date of death, loss-to-follow-up, or December 31, 2012, whichever was earliest. Occupational brain doses through 1997 were based on work history, historical data, and, for most years after the mid-1970s, individual film badge measurements. Radiation-related excess relative risks (ERRs) and 95% confidence intervals (CIs) were estimated from Poisson regression models adjusted for attained age and sex. RESULTS: Cumulative mean absorbed brain dose was 11.8 mGy (range 0–290.1 mGy). During follow-up (median 26.7 years), 193 technologists died of a malignant intracranial neoplasm. Based on models incorporating a five-year lagged cumulative brain dose, cumulative brain dose was not associated with malignant intracranial tumor mortality (overall ERR per 100 mGy=0.1, 95% CI

This study aimed to explore patient-, provider-, and system-level factors that may contribute to elevated risk of patient safety events among persons with serious mental illness (SMI). We conducted a medical record review of medical/surgical admissions in Maryland hospitals from 1994 to 2004 for a community-based sample of adults with SMI (N = 790 hospitalizations). We estimated the prevalence of multiple patient, provider, and system factors that could influence patient safety among persons with SMI. We conducted a case crossover analysis to examine the relationship between these factors and adverse patient safety events. Patients’ mental status, level of consciousness, disease severity, and providers’ lack of patient monitoring, delay/failure to seek consultation, lack of trainee supervision, and delays in care were positively associated with adverse patient safety events (p < 0.05). Efforts to reduce SMI-related patient safety risks will need to be multifaceted and address both patient- and provider-level factors.

Author(s): Cahoon, Elizabeth K; Nadyrov, Eldar A; Polyanskaya, Olga N; Yauseyenka, Vasilina V; Veyalkin, Ilya V; Yeudachkova, Tamara I; Maskvicheva, Tamara I; Minenko, Victor F; Liu, Wayne; Drozdovitch, Vladimir; Mabuchi, Kiyohiko; Little, Mark P; Zablotska, Lydia B; McConnell, Robert J; Hatch, Maureen; Peters, Kamau O; Rozhko, Alexander V; Brenner, Alina V | Abstract: ContextAlthough radiation exposure is an important predictor of thyroid cancer on diagnosis of a thyroid nodule, the relationship between childhood radiation exposure and thyroid nodules has not been comprehensively evaluated.ObjectiveTo examine the association between internal I-131 thyroid dose and thyroid nodules in young adults exposed during childhood.Design, setting, and participantsIn this cross-sectional study, we screened residents of Belarus aged ≤18 years at the time of the Chernobyl nuclear accident for thyroid disease (median age, 21 years) with thyroid palpation, ultrasonography, blood/urine analysis, and medical follow-up when appropriate. Eligible participants (N = 11,421) had intact thyroid glands and doses based on direct individual thyroid activity measurements.Main outcome measuresExcess odds ratios per Gray (EOR/Gy, scaled at age 5 years at exposure) for any thyroid nodule and for nodules grouped by cytology/histology, diameter size, and singularity.ResultsRisk of any thyroid nodule increased significantly with I-131 dose and, for a given dose, with younger age at exposure. The EOR/Gy (95% confidence intervals) for neoplastic nodules (3.82; 0.87 to 15.52) was significantly higher than for nonneoplastic nodules (0.32; l0.03 to 0.70) and did not vary by size; whereas the EOR/Gy for nonneoplastic nodules did vary by size (P = 0.02) and was 1.55 (0.36 to 5.46) for nodules ≥10 mm and 0.02 (l-0.02 to 0.70) for nodules l10 mm. EORs/Gy for single and multiple nodules were comparable.ConclusionsChildhood exposure to internal I-131 is associated with increased risk of neoplastic thyroid nodules of any size and nonneoplastic nodules ≥10 mm.

In April 1986, the Chernobyl nuclear accident resulted in wide-scale contamination of Belarus with significantly elevated levels of radioiodine isotopes, mainly iodine-131 (131I), and long-lived radiocaesium isotopes, mainly caesium-137 (137Cs). Various groups of the population were affected by exposure to ionising radiation, including pregnant women and their foetuses. This paper describes the methods and results related to the establishment of a cohort of 2965 Belarusian people exposed in utero due to Chernobyl fallout. The cohort consists of individuals whose mothers resided in the most radioactively contaminated areas in Belarus at the time of the accident. Prenatal and postnatal doses to the thyroid due to intake of 131I, external irradiation and ingestion of radiocaesium isotopes were estimated for all cohort members. Ongoing research on this unique cohort will provide important information on adverse health effects following prenatal and postnatal exposure to radioiodine and radiocaesium isotopes, for which available epidemiological data are scant.

BACKGROUND: Few well-established factors are associated with risk of amyotrophic lateral sclerosis (ALS). We comprehensively evaluate prescription drugs use in administrative health claims from U.S. Medicare beneficiaries in relation to ALS risk to generate hypotheses for further research. METHODS: This is a population-based case–control study of 10,450 U.S. Medicare participants (ages 66–89 years) diagnosed with ALS, based on Medicare Parts A and B fee-for-service claims, between 1 January 2008, and 31 December 2014, and 104,500 controls (1:10 ratio) frequency-matched on age, sex, and selection year. Odds ratios (ORs) for the ALS association with 685 prescription drugs were estimated using logistic regression models for both a one- and three-year lag period. Covariates included demographic characteristics and key comorbidities, among other factors. Prescription drug use was based on Medicare Part D claims. We adjusted for multiple comparisons using a Bonferroni correction. Additional a priori analyses of sex hormone drugs were also undertaken. RESULTS: In the large drug screen, we found 10 drugs significantly associated with lower ALS risk after the multiple-testing correction in a one-year and three-year lag analysis. These included several drugs for hypertension, diabetes, and cardiovascular disease. In a separate a priori inquiry of sex hormone drugs, tamoxifen was related to lower ALS risk, and testosterone to a higher risk in women. CONCLUSIONS: These associations warrant replication in databases that include information on the severity and duration of medical conditions underlying drug use, and drug use over a longer portion of individuals’ lifespans, to further help evaluate confounding by indication.

Although transgenerational effects of exposure to ionizing radiation have long been a concern, human research to date has been confined to studies of disease phenotypes in groups exposed to high doses and high dose rates, such as the Japanese atomic bomb survivors. Transgenerational effects of parental irradiation can be addressed using powerful new genomic technologies. In collaboration with the Ukrainian National Research Center for Radiation Medicine, the US National Cancer Institute, in 2014–2018, initiated a genomic alterations study among children born in selected regions of Ukraine to cleanup workers and/or evacuees exposed to low–dose-rate radiation after the 1986 Chornobyl (Chernobyl) nuclear accident. To investigate whether parental radiation exposure is associated with germline mutations and genomic alterations in the offspring, we are collecting biospecimens from father-mother-offspring constellations to study de novo mutations, minisatellite mutations, copy-number changes, structural variants, genomic insertions and deletions, methylation profiles, and telomere length. Genomic alterations are being examined in relation to parental gonadal dose, reconstructed using questionnaire and measurement data. Subjects are being recruited in exposure categories that will allow examination of parental origin, duration, and timing of exposure in relation to conception. Here we describe the study methodology and recruitment results and provide descriptive information on the first 150 families (mother-father-child(ren)) enrolled.

Radiation exposure is among the few factors known to be associated with risk of central nervous system (CNS) tumors. However, the patterns of radiation risk by histological type, sex or age are unclear. We evaluated radiation risks of first primary glioma, meningioma, schwannoma, and other or not otherwise specified (other/NOS) tumors in the Life Span Study (LSS) cohort of atomic bomb survivors. Cases diagnosed between 1958 and 2009 were ascertained through population-based cancer registries in Hiroshima and Nagasaki. To estimate excess relative risk per Gy (ERR/Gy), we fit rate models using Poisson regression methods. There were 285 CNS tumors (67 gliomas, 107 meningiomas, 49 schwannomas, and 64 other/NOS tumors) among 105,444 individuals with radiation dose estimates to the brain contributing 3.1 million person-years of observation. Based on a simple linear model without effect modification, ERR/Gy was 1.67 (95% confidence interval, CI: 0.12 to 5.26) for glioma, 1.82 (95% CI: 0.51 to 4.30) for meningioma, 1.45 (95% CI: −0.01 to 4.97) for schwannoma, and 1.40 (95% CI: 0.61 to 2.57) for all CNS tumors as a group. For each tumor type, the dose-response was consistent with linearity and appeared to be stronger among males than among females, particularly for meningioma (P = 0.045). There was also evidence that the ERR/Gy for schwannoma decreased with attained age (P = 0.002). More than 60 years after the bombings, radiation risks for CNS tumors continue to be elevated. Further follow-up is necessary to characterize the lifetime risks of specific CNS tumors following radiation exposure.

As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958-2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (-66% per decade, 95% CI: -88% to -32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (-1.93 power of attained age, 95% CI: -2.94 to -0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.

Statins are commonly prescribed drugs that have been inconsistently associated with amyotrophic lateral sclerosis (ALS) risk. We examined associations between ALS risk and overall statin use, statin categories based on lipophilicity and other cholesterol-lowering medications, in Medicare beneficiaries.In this nation-wide population-based case-control study, 10,450 Medicare participants (ages 66-89 years) diagnosed with ALS, using Medicare Parts A and B claims, between 1 January 2008 and 31 December 2014, were frequency-matched to 104,500 controls on age, sex, and selection year. Odds ratios (ORs) for the association between statins and ALS were estimated using logistic regression models. Covariates included dyslipidemia, other comorbidities, age, sex, race, proxies for smoking and obesity, Medicare use, and indicators of socioeconomic status. Statin use derived from Medicare Part D claims. Non-statin cholesterol-lowering drugs were evaluated as comparison drugs.ALS risk was reduced with statin use (OR = 0.87 (95% confidence interval (CI) = 0.83-0.91)). While risk was unrelated to three cholesterol-lowering medications (nitrates, bile acid sequestrants, and ezetimibe), it was associated with fibrates (OR = 0.88 (95% CI = 0.80-0.97)). Risk for lipophilic statins was slightly lower than for other statins. ALS risk was lower in all statin categories for dyslipidemic individuals, but only lipophilic statins were associated with lower risk in non-dyslipidemic individuals and demonstrated an inverse trend with duration.Our findings suggest that statins are associated with lower ALS risk and offer new evidence that fibrates may be related to lower risk. However, we were unable to fully adjust for smoking and body mass index.

This study explored the risk of patient safety events and associated nonfatal physical harms and mortality in a cohort of persons with serious mental illness. This group experiences high rates of medical comorbidity and premature mortality and may be at high risk of adverse patient safety events.Medical record review was conducted for medical-surgical hospitalizations occurring during 1994-2004 in a community-based cohort of Maryland adults with serious mental illness. Individuals were eligible if they died within 30 days of a medical-surgical hospitalization and if they also had at least one prior medical-surgical hospitalization within five years of death. All admissions took place at Maryland general hospitals. A case-crossover analysis examined the relationships among patient safety events, physical harms, and elevated likelihood of death within 30 days of hospitalization.A total of 790 hospitalizations among 253 adults were reviewed. The mean number of patient safety events per hospitalization was 5.8, and the rate of physical harms was 142 per 100 hospitalizations. The odds of physical harm were elevated in hospitalizations in which 22 of the 34 patient safety events occurred (p.05), including medical events (odds ratio [OR]=1.5, 95% confidence interval [CI]=1.3-1.7) and procedure-related events (OR=1.6, CI=1.2-2.0). Adjusted odds of death within 30 days of hospitalization were elevated for individuals with any patient safety event, compared with those with no event (OR=3.7, CI=1.4-10.3).Patient safety events were positively associated with physical harm and 30-day mortality in nonpsychiatric hospitalizations for persons with serious mental illness.

Background: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality. Methods: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983–2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983–2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors. Results: Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03–0.39) with similar patterns for mortality among technologists born before 1930. Conclusions: Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

A few studies have examined the association between vitamin D and telomere length, and fewer still have examined the relationship in black or male populations. We investigated the cross-sectional association between the vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) concentration in plasma and relative leucocyte telomere length (LTL) in 1154 US radiologic technologists who were 48–93 years old (373 white females, 278 white males, 338 black females, 165 black males). Plasma 25(OH)D concentration was measured by the chemiluminescence immunoassay, and relative LTL was measured by quantitative PCR. Logistic regression was used to obtain OR and 95 % CI for long v. short (based on median) LTL in relation to continuous 25(OH)D, quartiles of 25(OH)D and 25(OH)D deficiency. We found no significant association between continuous 25(OH)D and long LTL in all participants (Ptrend=0·440), nor in white females (Ptrend=0·845), white males (Ptrend=0·636), black females (Ptrend=0·967) or black males (Ptrend=0·484). Vitamin D deficiency (defined as 25(OH)DP=0·024), but not in other groups. In this population, we found little evidence to support associations between 25(OH)D and long LTL over the entire range of 25(OH)D in the overall study population or by sex and race.

Purpose UV radiation exposure is the primary risk factor for basal cell carcinoma (BCC), the most common human malignancy. Although the photosensitizing properties of estrogens have been recognized for decades, few studies have examined the relationship between reproductive factors or exogenous estrogen use and BCC. Methods Using data from the US Radiologic Technologists Study, a large, nationwide, prospective cohort, we assessed the relationship between reproductive factors, exogenous estrogen use, and first primary BCC while accounting for sun exposure, personal sun sensitivity, and lifestyle factors for geographically dispersed women exposed to a wide range of ambient UV radiation. Results Elevated risk of BCC was associated with late age at natural menopause (hazard ratio [HR] for ≥ 55 years v 50 to 54 years, 1.50; 95% CI, 1.04 to 2.17) and any use of menopausal hormone therapy (MHT; HR, 1.16; 95% CI, 1.03 to 1.30; P for trend for duration = .001). BCC risk was most increased among women reporting natural menopause who used MHT for 10 or more years versus women who never used MHT (HR, 1.97; 95% CI, 1.35 to 2.87). Risk of BCC was not associated with age at menarche, parity, age at first birth, infertility, use of diethylstilbestrol by participant's mother, age at hysterectomy, or use of oral contraceptives. Conclusion These analyses confirm a previous finding of increased risk of BCC associated with MHT. Novel findings of increased BCC risk associated with MHT in women experiencing natural menopause and for late age at natural menopause warrant further investigation. Users of MHT may constitute an additional high-risk group in need of more frequent skin cancer screening.

The importance of reproductive history in breast tissue development and etiology of sporadic breast cancer in females is well established. However, there is limited evidence of factors, other than age, that modify risk of radiation-related breast cancer. In this study, we evaluated breast cancer incidence in the Life Span Study cohort of atomic bomb survivors, adding 11 years of follow-up and incorporating reproductive history data. We used Poisson regression models to describe radiation risks and modifying effects of age and reproductive factors. Among 62,534 females, we identified 1,470 breast cancers between 1958 and 2009. Of 397 new cases diagnosed since 1998, 75% were exposed before age 20. We found a strong linear dose response with excess relative risk (ERR) of 1.12 per Gy [95% confidence interval (CI): 0.73 to 1.59] for females at age 70 after exposure at age 30. The ERR decreased with increasing attained age ( P = 0.007) while excess absolute rate (EAR) increased with attained age up to age 70 ( P0.001). Age at menarche was a strong modifier of the radiation effect: for a given dose, both the ERR and EAR decreased with increasing age at menarche ( P = 0.007 and P0.001). Also, independently, age-at-exposure effects on ERR and EAR differed before and after menarche ( P = 0.043 and P = 0.015, respectively, relative to log-linear trends), with highest risks for exposures around menarche. Despite the small number of male breast cancers (n = 10), the data continue to suggest a dose response (ERR per Gy = 5.7; 95% CI: 0.3 to 30.8; P = 0.018). Persistently increased risk of female breast cancer after radiation exposure and its modification pattern suggests heightened breast sensitivity during puberty.

ObjectivesTo assess radiation exposure-related work history and risk of cataract and cataract surgery among radiologic technologists assisting with fluoroscopically guided interventional procedures (FGIP).MethodsThis retrospective study included 35 751 radiologic technologists who reported being cataract-free at baseline (1994–1998) and completed a follow-up questionnaire (2013–2014). Frequencies of assisting with 21 types of FGIP and use of radiation protection equipment during five time periods (before 1970, 1970–1979, 1980–1989, 1990–1999, 2000–2009) were derived from an additional self-administered questionnaire in 2013–2014. Multivariable-adjusted relative risks (RRs) for self-reported cataract diagnosis and cataract surgery were estimated according to FGIP work history.ResultsDuring follow-up, 9372 technologists reported incident physician-diagnosed cataract; 4278 of incident cases reported undergoing cataract surgery. Technologists who ever assisted with FGIP had increased risk for cataract compared with those who never assisted with FGIP (RR: 1.18, 95% CI 1.11 to 1.25). Risk increased with increasing cumulative number of FGIP; the RR for technologists who assisted with >5000 FGIP compared with those who never assisted was 1.38 (95% CI 1.24 to 1.53; p trend 3 feet (>0.9 m) (RRs for >5000 at ≤3 feet vs never FGIP were 1.48, 95% CI 1.27 to 1.74 and 1.15, 95% CI 0.98 to 1.35, respectively; pdifference=0.04). Similar risks, although not statistically significant, were observed for cataract surgery.ConclusionTechnologists who reported assisting with FGIP, particularly high-volume FGIP within 3 feet of the patient, had increased risk of incident cataract. Additional investigation should evaluate estimated dose response and medically validated cataract type.

Objective To assess whether personal medical diagnostic procedures over life, but particularly those associated with exposure in adulthood, were associated with increased thyroid cancer risk. Design Participants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from the date of first mailed questionnaire survey completed during 1983–1989 to the earliest date of self-reported diagnosis of thyroid cancer or of any other cancer than non-melanoma skin cancer (NMSC) in any of three subsequent questionnaires up to the last in 2012–2014. Setting US nationwide, occupational cohort. Participants US radiologic technologists with exclusion of: those who reported a previous cancer apart from NMSC on the first questionnaire; those who reported a cancer with an unknown date of diagnosis on any of the questionnaires; and those who did not respond to both the first questionnaire and at least one subsequent questionnaire. Primary outcome measure We used Cox proportional hazards models with age as timescale to compute HRs and 95% CI for thyroid cancer in relation to cumulative 5-year lagged diagnostic thyroid dose. Results There were 414 self-reported thyroid cancers (n=275 papillary) in a cohort of 76 415 persons. Cumulative thyroid dose was non-significantly positively associated with total (excess relative risk/Gy=2.29 (95% CI −0.91 to 7.01, p=0.19)) and papillary thyroid cancer (excess relative risk/Gy=4.15 (95% CI −0.39, 11.27, p=0.08)) risk. These associations were not modified by age at, or time since, exposure and were independent of occupational exposure. Conclusion Our study provides weak evidence that thyroid dose from diagnostic radiation procedures over the whole of life, in particular associated with exposure in adulthood, influences adult thyroid cancer risk.

International audience; It has long been known that relatively high-dose ionising radiation exposure (> 1 Gy) can induce cataract, but there has been no evidence that this occurs at low doses (< 100 mGy). To assess low-dose risk, participants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from date of mailed questionnaire survey completed during 1994-1998 to the earliest of self-reported diagnosis of cataract/cataract surgery, cancer other than non-melanoma skin, or date of last survey (up to end 2014). Cox proportional hazards models with age as timescale were used, adjusted for a priori selected cataract risk factors (diabetes, body mass index, smoking history, race, sex, birth year, cumulative UVB radiant exposure). 12,336 out of 67,246 eligible technologists reported a history of diagnosis of cataract during 832,479 person years of follow-up, and 5509 from 67,709 eligible technologists reported undergoing cataract surgery with 888,420 person years of follow-up. The mean cumulative estimated 5-year lagged eye-lens absorbed dose from occupational radiation exposures was 55.7 mGy (interquartile range 23.6-69.0 mGy). Five-year lagged occupational radiation exposure was strongly associated with self-reported cataract, with an excess hazard ratio/mGy of 0.69 é— 10ˆ’3 (95% CI 0.27 é— 10ˆ’3 to 1.16 é— 10ˆ’3, p < 0.001). Cataract risk remained statistically significant (p = 0.030) when analysis was restricted to < 100 mGy cumulative occupational radiation exposure to the eye lens. A non-significantly increased excess hazard ratio/mGy of 0.34 é— 10ˆ’3 (95% CI ˆ’ 0.19 é— 10ˆ’3 to 0.97 é— 10ˆ’3, p = 0.221) was observed for cataract surgery. Our results suggest that there is excess risk for cataract associated with radiation exposure from low-dose and low dose-rate occupational exposures. © 2018, This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection.

Purpose: We examine the risk of cataract and cataract surgery with measures of ultraviolet radiation (UVR) exposure and UVR sensitivity in a large, nationwide population of indoor workers. Methods: Participants from the US Radiologic Technologists Study were followed from age at baseline survey (2003–2005) to age at earliest of cataract diagnosis, cataract surgery, or completion of last survey (2012–2013). UVR-related factors included satellite-based ambient UVR linked to lifetime residences, time spent outdoors across various age periods, history of blistering sunburns, prior diagnosis of keratinocyte carcinoma, and iris color. We used Cox proportional hazards models with age as timescale to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for cataract and cataract surgery. Results: Participants had a median age of entry of 54.0 years, were 80.0% female, and 95.7% white. Of the 44, 891 eligible participants, 9399 cases of cataract and 3826 cases of cataract surgery were reported. Ambient UVR (quintile 5 vs. 1) was associated with an increased risk of cataract (HR = 1.08; 95% CI: 1.01–1.16) and cataract surgery (HR = 1.16; 95% CI: 1.05–1.29). Lifetime average time spent outdoors was not associated with cataract risk. History of blistering sunburns before and after age 15, but not previous keratinocyte carcinoma diagnosis was associated with both cataract and cataract surgery. Conclusion: Our results suggest a modest role for residence-based ambient UVR and cataract risk among indoor workers in the United States.

The Earth's surface is warming and animal studies have shown higher temperatures promote ultraviolet radiation (UVR) skin carcinogenesis. There are, however, no population studies of long-term temperature exposure and basal cell carcinoma (BCC) risk. We linked average lifetime summer ambient temperatures (based on weather station data) and satellite-based UVR estimates to self-reported lifetime residences in the U.S. Radiologic Technologists' cohort. We assessed the relationship between time-dependent average lifetime summer ambient temperature (20-year lag) in quintiles and BCC in whites, using Cox proportional hazards regression. Risks were adjusted for time-dependent lagged average lifetime UVR and time outdoors, body mass index, eye color, and sex (baseline hazard stratified on birth cohort). During a median 19.4 years follow-up, we identified 3,556 BCC cases. There was no significant trend in risk between temperature and BCC. However, BCC risk was highest in the fourth quintile of temperature (Q4 vs. Q1; hazards ratio (HR)=1.18; 95% confidence interval (CI) = 1.06–1.31, p-trend =0.09). BCC risk was strongly related to average lifetime ambient UVR exposure (Q5 vs. Q1; HR = 1.54 (95% CI = 1.35–1.75, p-trend=

BackgroundSerum thyroglobulin (Tg) is associated with the presence of thyroid disease and has been proposed as a biomarker of iodine status. Few studies have examined factors related to serum Tg in populations environmentally exposed to ionizing radiation and living in regions with endemic mild-to-moderate iodine deficiency.MethodsWe screened 10,430 individuals who were living in Ukraine and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant accident for thyroid disease from 2001 to 2003. We estimated the percent change (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose, and indicators of thyroid structure and function using linear regression. We also examined these relationships for individuals with and without indications of thyroid abnormality.ResultsMean and median serum Tg levels were higher among participants with abnormal thyroid structure/function. Percent change in serum Tg increased among females, smokers and with older age (p-values

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members’ prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (−1.0 cm/Gy, P = 0.005) and chest circumference (−0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (−0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.