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Inconsistent epidemiologic findings on cigarette smoking and female breast cancer risk may reflect insufficient assessment of smoking onset and amount relative to reproductive events. To determine the risk of breast cancer associated with smoking during different periods of reproductive life, the authors evaluated 906 incident breast cancer cases in a nationwide cohort of 56,042 female US radiologic technologists (1983-1998) who responded to two questionnaire surveys. After they accounted for age, birth cohort, and established breast cancer risk factors, smoking-related breast cancer risks differed by smoking during three reproductive time periods (p = 0.003), with a statistically significant 3% increase per pack-year of smoking between menarche and first childbirth (relative risk = 1.03, 95% confidence interval: 1.02, 1.05) and no significant association for smoking after first childbirth. Risk also increased with younger age at smoking initiation (p-trend = 0.06), after adjustment for pack-years of smoking before and after first childbirth, indicating an independent effect of age at smoking initiation. The findings from this study suggest that sensitivity of the female breast to tobacco carcinogens is increased during adolescence and early adulthood but decreases after first childbirth, when most breast tissue has terminally differentiated. [ABSTRACT FROM AUTHOR]

We evaluated breast cancer mortality through 1997 among 69 525 female radiologic technologists who were certified in the United States from 1926 through 1982 and who responded to our questionnaire. Risk of breast cancer mortality was examined according to work history and practices and was adjusted for known risk factors. Breast cancer mortality risk was highest among women who were first employed as radiologic technologists prior to 1940 (relative risk [RR] = 2.92, 95% confidence interval [CI] = 1.22 to 7.00) compared with risk of those first employed in 1960 or later and declined with more recent calendar year of first employment (P for trend =.002). Breast cancer mortality risk increased with increasing number of years of employment as a technologist prior to 1950 (P for trend =.018). However, risk was not associated with the total number of years a woman worked as a technologist. Technologists who first performed fluoroscopy (RR = 1.69, 95% CI = 1.02 to 3.11) and multifilm procedures (RR = 1.87, 95% CI = 1.04 to 3.34) before 1950 had statistically significantly elevated risks compared with technologists who first performed these procedures in 1960 or later. The high risks of breast cancer mortality for women exposed to occupational radiation prior to 1950 and the subsequent decline in risk are consistent with the dramatic reduction in recommended radiation exposure limits over time. [ABSTRACT FROM AUTHOR]

Purpose: To illustrate the value of cohort studies to assess trends in chronic disease risk factors.Methods: In collaboration with the American Registry of Radiologic Technologists and the University of Minnesota, the National Cancer Institute initiated a cohort study of cancer among radiologic technologists. More than 90,000 technologists who responded to a mailed questionnaire were grouped into ten birth cohorts from before 1920 through 1960 and later, and stratified by self-reported racial/ethnic groups. Trends in height, smoking, and reproductive factors were analyzed.Results: Among the trends observed were that the proportion of young men (< 18 years) smoking generally fell in each birth cohort after 1925, whereas the proportion of young women smoking rose for those born after 1950. Among women born since 1940, the mean age at menarche for white women has remained at 12.5 years, but has declined among black and Asian/Pacific Islander women. Recent birth cohorts (since 1955) show among the highest mean ages at birth of first child (> 26 years), highest rates of nulliparity at age 25 (>/= 63 %), and lowest mean parity levels (< or = 1.7) compared with earlier cohorts.Conclusion: Analyses of large cohorts can clarify birth cohort trends in chronic disease risk factors. [ABSTRACT FROM AUTHOR]

Background: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear., Methods: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted., Results: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards., Discussion: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

In the Japanese atomic bomb survivors, risk of lung cancer has been shown to increase with greater acute exposure to ionizing radiation. Although similar findings have been observed in populations exposed to low-dose, protracted radiation, such studies lack information on cigarette smoking history, a potential confounder. In a cohort of 106 068 U.S. radiologic technologists, we examined the association between estimated cumulative lung absorbed dose from occupational radiation exposure and lung cancer mortality. Poisson regression models, adjusted for attained age, sex, birth cohort, pack-years smoked and years since quitting smoking, were used to calculate linear excess relative risks (ERR) per 100 mGy, using time-dependent cumulative lung absorbed dose, lagged 10 years. Mean cumulative absorbed dose to the lung was 25 mGy (range: 0-810 mGy). During the 1983 to 2012 follow-up, 1090 participants died from lung cancer. Greater occupational radiation lung dose was not associated with lung cancer mortality overall (ERR per 100 mGy: -0.02, 95% CI: <0-0.13). However, significant dose-response relationships were observed for some subgroups, which might be false-positive results given the number of statistical tests performed. As observed in other studies of radiation and smoking, the interaction between radiation and smoking appeared to be sub-multiplicative with an ERR per 100 mGy of 0.41 (95% CI: 0.01-1.15) for those who smoked <20 pack-years and -0.03 (95% CI: <0-0.15) for those who smoked ≥20 pack-years. Our study provides some evidence that greater protracted radiation exposure in the low-dose range is positively associated with lung cancer mortality., (© 2020 UICC.)

Objectives: To evaluate cumulative occupational radiation dose response and haematopoietic malignancy mortality risks in the US radiologic technologist cohort., Methods: Among 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., Results: Deaths 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 <-0.02 to 0.24, p-trend>0.5, 85 cases) or leukaemia excluding CLL (ERR=0.05, 95% CI <-0.09 to 0.24, p-trend=0.21, 155 cases). No significant dose-response trends were observed overall for CLL (ERR<-0.023, 95% CI <-0.025 to 0.18, p-trend=0.45, 32 cases), non-Hodgkin lymphoma (ERR=0.03, 95% CI <-0.2 to 0.18, p-trend=0.4, 201 cases) or multiple myeloma (ERR=0.003, 95% CI -0.02 to 0.16, p-trend>0.5, 112 cases). Findings did not differ significantly by demographic factors, smoking or specific radiological procedures performed., Conclusion: After follow-up averaging 22 years, there was little evidence of a relationship between occupational radiation exposure and myeloid or lymphoid haematopoietic neoplasms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism., Objective: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism., Design, Setting, and Participants: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18 805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019., Exposures: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland)., Main Outcomes and Measures: Site-specific and all solid-cancer mortality., Results: A total of 18 805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14 671 [78.0%]), and most had a Graves disease diagnosis (17 615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P = .002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P = .04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P = .01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur., Conclusions and Relevance: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

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 × 10 -3 (95% CI 0.27 × 10 -3 to 1.16 × 10 -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 × 10 -3 (95% CI - 0.19 × 10 -3 to 0.97 × 10 -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.

Although childhood exposure to ionizing radiation is a well-established risk factor for thyroid cancer, the risk associated with adulthood exposure remains unclear. We prospectively examined the association between cumulative, low-to-moderate dose occupational radiation exposure to the thyroid and thyroid cancer incidence in the U.S. Radiologic Technologists cohort. The study included 89,897 members who completed at least two of four mailed questionnaires and were cancer-free at the time of the first questionnaire. Cumulative occupational thyroid radiation dose (mean = 57 mGy, range = 0-1,600 mGy) was estimated based on self-reported work histories, historical data and, during the years 1960-1997, 783,000 individual film badge measurements. During follow-up, we identified 476 thyroid cancer cases. We used Poisson regression to estimate excess relative risk of thyroid cancer per 100 milliGray (ERR/100 mGy) absorbed dose to the thyroid gland. After adjusting for attained age, sex, birth year, body mass index and pack-years smoked, we found no association between thyroid dose and thyroid cancer risk (ERR/100 mGy = -0.05, 95% CI <-0.10, 0.34). In this large cohort study of radiologic technologists, protracted, low-to-moderate dose ionizing radiation exposure to the thyroid gland in adulthood was not associated with an increased risk of thyroid cancer., (© 2018 UICC.)

Background: Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years)., Methods: In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014. We evaluated leukaemia and myeloid malignancy outcomes in these cohorts with the relevant International Classification of Diseases and International Classification of Diseases for Oncology definitions. The cohorts included had not been treated for malignant disease, had reported at least five cases of the relevant haematopoietic neoplasms, and estimated individual active bone marrow (ABM) doses. We restricted analysis to individuals who were younger than 21 years at first irradiation who had mean cumulative ABM doses of less than 100 mSv. Dose-response models were fitted by use of Poisson regression. The data were received in fully anonymised form by the statistical analyst., Findings: We identified nine eligible cohorts from Canada, France, Japan, Sweden, the UK, and the USA, including 262 573 people who had been exposed to less than 100 mSv enrolled between June 4, 1915, and Dec 31, 2004. Mean follow-up was 19·63 years (SD 17·75) and mean cumulative ABM dose was 19·6 mSv (SD 22·7). 154 myeloid malignancies were identified (which included 79 acute myeloid leukaemias, eight myelodysplastic syndromes, and 36 chronic myeloid leukaemias, in addition to other unspecified myeloid malignancies) and 40 acute lymphoblastic leukaemias, with 221 leukaemias (including otherwise unclassified leukaemias but excluding chronic lymphocytic leukaemia) identified overall. The fitted relative risks at 100 mSv were 3·09 (95% CI 1·41-5·92; p trend =0·008) for acute myeloid leukaemia and myelodysplastic syndromes combined, 2·56 (1·09-5·06; p trend =0·033) for acute myeloid leukaemia, and 5·66 (1·35-19·71; p trend =0·023) for acute lymphoblastic leukaemia. There was no clear dose-response for chronic myeloid leukaemia, which had a relative risk at 100 mSv of 0·36 (0·00-2·36; p trend =0·394). There were few indications of between-cohort heterogeneity or departure from linearity. For acute myeloid leukaemia and myelodysplastic syndromes combined and for acute lymphoblastic leukaemia, the dose-responses remained significant for doses of less than 50 mSv. Excess absolute risks at 100 mSv were in the range of 0·1-0·4 cases or deaths per 10 000 person-years., Interpretation: The risks of acute myeloid leukaemia and acute lymphoblastic leukaemia were significantly increased after cumulative doses of ionising radiation of less than 100 mSv in childhood or adolescence, with an excess risk also apparent for cumulative radiation doses of less than 50 mSv for some endpoints. These findings support an increased risk of leukaemia associated with low-dose exposure to radiation and imply that the current system of radiological protection is prudent and not overly protective., Funding: National Cancer Institute Intramural Research Program, National Cancer Institute, and US National Institutes for Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Technologists working in nuclear medicine (NM) are exposed to higher radiation doses than most other occupationally exposed populations. The aim of this study was to estimate the risk of cancer in NM technologists in relation to work history, procedures performed and radioprotection practices., Methods: From the US Radiologic Technologists cohort study, 72 755 radiologic technologists who completed a 2003-2005 questionnaire were followed for cancer mortality through 31 December 2012 and for cancer incidence through completion of a questionnaire in 2012-2013. Multivariable-adjusted models were used to estimate HRs for total cancer incidence and mortality by history of ever performing NM procedures and frequency of performing specific diagnostic or therapeutic NM procedures and associated radiation protection measures by decade., Results: During follow-up (mean=7.5 years), 960 incident cancers and 425 cancer deaths were reported among the 22 360 technologists who worked with NM procedures. We observed no increased risk of cancer incidence (HR 0.96, 95% CI 0.89 to 1.04) or death (HR 1.05, 95% CI 0.93 to 1.19) among workers who ever performed NM procedures. HRs for cancer incidence but not mortality were higher for technologists who began performing therapeutic procedures in 1960 and later compared with the 1950s. Frequency of performing diagnostic or therapeutic NM procedures and use of radioprotection measures were not consistently associated with cancer risk. No clear associations were observed for specific cancers, but results were based on small numbers., Conclusion: Cancer incidence and mortality were not associated with NM work history practices, including greater frequency of procedures performed., Competing Interests: Competing interests: None declred., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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: 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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type., Methods: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression., Results: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR ≥7 drinks/day  = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR ≥5 drinks/day  = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR >0-<0.5 drinks/day  = 0.77, 95% CI: 0.67-0.89; HR >0.5-<1 drinks/day  = 0.57, 95% CI: 0.44-0.73; HR 1-<3 drinks/day  = 0.71, 95% CI: 0.58-0.87), but not ICC., Conclusions: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.

Purpose To estimate the risk of cataract in a cohort of nuclear medicine (NM) radiologic technologists on the basis of their work histories and radiation protection practices. Materials and Methods In the years 2003-2005 and 2012-2013, 42 545 radiologic technologists from a U.S. prospective study completed questionnaires in which they provided information regarding their work histories and cataract histories. Cox proportional hazards models, stratified according to birth-year cohort (born before 1940 or born in 1940 or later) and adjusted for age, sex, and race, were used to estimate hazard ratios (HRs) for the risk of cataract in radiologic technologists according to NM work history practices according to decade. Results During the follow-up period (mean follow-up, 7½ years), 7137 incident cataracts were reported. A significantly increased risk of cataract (HR, 1.08; 95% confidence interval [CI]: 1.03, 1.14) was observed among workers who performed an NM procedure at least once-as opposed to never. Risks of cataract were increased in the group who had performed a diagnostic (HR, 1.07; 95% CI: 1.01, 1.12) or therapeutic (HR, 1.10; 95% CI: 1.04, 1.17) NM procedure. Risks were higher for those who had first performed diagnostic NM procedures in the 1980s to early 2000s (HR, 1.30; 95% CI: 1.08, 1.58) and those who had performed therapeutic NM procedures in the 1970s (HR, 1.11; 95% CI: 1.01, 1.23) and in the 1980s to early 2000s (HR, 1.14; 95% CI: 1.02, 1.29). With the exception of a significantly increased risk associated with performing therapeutic NM procedures without shielding the radiation source in the 1980s (HR, 1.32; 95% CI: 1.04, 1.67), analyses revealed no association between cataract risk and specific radiation protection technique used. Conclusion An increased risk of cataract was observed among U.S. radiologic technologists who had performed an NM procedure at least once. This association should be examined in future studies incorporating estimated lens doses. © RSNA, 2017.

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: The prevalence of hyperthyroidism and hypothyroidism is 0.5-4% in iodine-replete communities, but it is 5-10 times higher in women than in men. Those conditions are associated with a broad range of metabolic disorders and cardiovascular diseases. Biological evidence of a role of thyroid hormones in carcinogenesis also exists. However, the association between thyroid dysfunction and cardiovascular disease or cancer mortality risk remains controversial. In a large cohort of women, the associations of hyperthyroidism and hypothyroidism with cause-specific mortality were evaluated after nearly 30 years of follow-up., Methods: The prospective study included 75,076 women aged 20-89 years who were certified as radiologic technologists in the United States in 1926-1982, completed baseline questionnaires in 1983-1998 from which medical history was ascertained, and reported no malignant disease or benign thyroid disease except thyroid dysfunction. A passive follow-up of this cohort was performed through the Social Security Administration database and the National Death Index-Plus. Cause-specific mortality risks were compared according to self-reported thyroid status, with proportional hazards models adjusted for baseline year and age, race/ethnicity, body mass index, family history of breast cancer, and life-style and reproductive factors., Results: During a median follow-up of 28 years, 2609 cancer, 1789 cardiovascular or cerebrovascular, and 2442 other non-cancer deaths were recorded. Women with hyperthyroidism had an elevated risk of breast cancer mortality after 60 years of age (hazard ratio [HR] = 2.04 [confidence interval (CI) 1.16-3.60], 13 cases in hyperthyroid women) compared to women without thyroid disease. Hypothyroid women had increased mortality risks for diabetes mellitus (HR = 1.58 [CI 1.03-2.41], 27 cases in hypothyroid women), cardiovascular disease (HR = 1.20 [CI 1.01-1.42], 179 cases), and cerebrovascular disease (HR = 1.45 [CI 1.01-2.08], 35 cases, when restricting the follow-up to ≥10 years after baseline). Other causes of death were not associated with hyperthyroidism or hypothyroidism, though there was a suggestion of an elevated risk of ovarian cancer mortality in hyperthyroid women based on very few cases., Conclusion: The excess mortality risks observed in a large, prospective 30-year follow-up of patients with thyroid dysfunction require confirmation, and, if replicated, further investigation will be needed because of the clinical implications.

Objective: Childhood exposure to acute, high-dose radiation has consistently been associated with risk of benign and malignant intracranial tumors of the brain and CNS, but data on risks of adulthood exposure to protracted, low-to-moderate doses of radiation are limited. In a large cohort of radiologic technologists, we quantified the association between protracted, low-to-moderate doses of radiation and malignant intracranial tumor mortality., Materials and Methods: The study population included 83,655 female and 26,642 male U.S. radiologic technologists who were certified for at least 2 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% CIs were estimated from Poisson regression models adjusted for attained age and sex., Results: Cumulative mean absorbed brain dose was 12 mGy (range, 0-290 mGy). During follow-up (median, 26.7 years), 193 technologists died of a malignant intracranial neoplasm. Based on models incorporating a 5-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, < -0.3 to 1.5). No effect modification was observed by sex or birth cohort., Conclusion: In this nationwide cohort of radiologic technologists, cumulative occupational radiation exposure to the brain was not associated with malignant intracranial tumor mortality.

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.

The authors evaluated historical patterns in the types of procedures performed in diagnostic and therapeutic nuclear medicine and the associated radiation safety practices used from 1945-2009 in a sample of U.S. radiologic technologists. In 2013-2014, 4,406 participants from the U.S. Radiologic Technologists (USRT) Study who previously reported working with medical radionuclides completed a detailed survey inquiring about the performance of 23 diagnostic and therapeutic radionuclide procedures and the use of radiation safety practices when performing radionuclide procedure-related tasks during five time periods: 1945-1964, 1965-1979, 1980-1989, 1990-1999, and 2000-2009. An overall increase in the proportion of technologists who performed specific diagnostic or therapeutic procedures was observed across the five time periods. Between 1945-1964 and 2000-2009, the median frequency of diagnostic procedures performed substantially increased (from 5 wk to 30 wk), attributable mainly to an increasing frequency of cardiac and non-brain PET scans, while the median frequency of therapeutic procedures performed modestly decreased (from 4 mo to 3 mo). Also a notable increase was observed in the use of most radiation safety practices from 1945-1964 to 2000-2009 (e.g., use of lead-shielded vials during diagnostic radiopharmaceutical preparation increased from 56 to 96%), although lead apron use dramatically decreased (e.g., during diagnostic imaging procedures, from 81 to 7%). These data describe historical practices in nuclear medicine and can be used to support studies of health risks for nuclear medicine technologists.

Objective: The purpose of this study was to examine risks of cancer incidence and mortality among U.S. radiation technologists performing or assisting with fluoroscopically guided interventional procedures., Subjects and Methods: A nationwide prospective cohort of 90,957 radiologic technologists, who responded to a 1994-1998 survey that collected information on whether they had ever worked with fluoroscopically guided interventional procedures, was followed through completion of a subsequent cohort survey during 2003-2005 (for cancer incidence) or December 31, 2008 (for cancer mortality). Sex-adjusted hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazards models for incidence and mortality from all cancers other than nonmelanoma skin cancer and for specific cancer outcomes in participants who reported ever performing fluoroscopically guided interventional procedures compared with technologists who never performed these procedures., Results: The analysis showed an approximately twofold increased risk of brain cancer mortality (HR, 2.55; 95% CI, 1.48-4.40) and modest elevations in incidence of melanoma (HR, 1.30; 95% CI, 1.05-1.61) and in breast cancer incidence (HR, 1.16; 95% CI, 1.02-1.32) but not mortality (HR, 1.07; 95% CI, 0.69-1.66) among technologists who performed fluoroscopically guided interventional procedures compared with those who never performed these procedures. Although there was a small suggestive increase in incidence of all cancers combined, excluding nonmelanoma skin cancers (HR, 1.08; 95% CI, 1.00-1.17), mortality from all cancers combined, excluding nonmelanoma skin cancers, was not elevated (HR, 1.00; 95% CI, 0.88-1.14). We similarly observed no elevated risk of cancers of the thyroid, skin other than melanoma, prostate, lung, or colon and rectum or of leukemia that was not chronic lymphocytic leukemia among workers who performed fluoroscopically guided interventional procedures., Conclusion: We observed elevated risks of brain cancer, breast cancer, and melanoma among technologists who performed fluoroscopically guided interventional procedures. Although exposure to low-dose radiation is one possible explanation for these increased risks, these results may also be due to chance or unmeasured confounding by nonradiation risk factors. Our results must be confirmed in other studies, preferably with individual radiation dose data.

Objectives: Although fluoroscopically guided interventional procedures (FGIP) have provided major advances in the treatment of various common diseases, radiation exposures associated with these procedures may cause adverse health effects in workers. We assess risk of circulatory disease incidence and mortality in medical radiation workers performing FGIP., Methods: A US nationwide prospective cohort study of 90,957 radiologic technologists who completed a cohort survey during 1994-1998 was followed until completion of a subsequent survey during 2003-2005 for circulatory disease incidence, or until 31 December 2008 for mortality. Incidence analyses were restricted to the 63,482 technologists who completed both the second survey (1994-1998) and the third survey (2003-2005). Cox proportional hazards models were used to assess adjusted HR and 95% CIs for mortality from all causes, all circulatory diseases, all heart diseases, ischaemic heart disease, stroke, acute myocardial infarction and hypertension in participants who reported ever performing FGIP compared to technologists who never performed FGIP procedures. Adjusted HRs were calculated for self-reported hypertension, stroke and myocardial infarction., Results: We observed a 34% increase in stroke incidence (HR=1.34, 95% CI 1.10 to 1.64) in technologists who performed FGIP compared to those who never performed these procedures. Mortality from stroke was also modestly elevated, although not statistically significant (HR=1.22, 95% CI 0.85 to 1.73). We observed no statistically significant excess risks of incidence or mortality from any other outcome evaluated., Conclusions: Our finding of elevated risk of stroke in workers performing FGIP needs to be confirmed in studies with individual radiation dose data, but nonetheless underlines the need to keep radiation exposure as low as reasonably achievable without compromising key diagnostic information., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To determine risk for incident basal cell carcinoma from cumulative low-dose ionising radiation in the US radiologic technologist cohort., Methods: We analysed 65,719 Caucasian technologists who were cancer-free at baseline (1983-1989 or 1994-1998) and answered a follow-up questionnaire (2003-2005). Absorbed radiation dose to the skin in mGy for estimated cumulative occupational radiation exposure was reconstructed for each technologist based on badge dose measurements, questionnaire-derived work history and protection practices, and literature information. Radiation-associated risk was assessed using Poisson regression and included adjustment for several demographic, lifestyle, host and sun exposure factors., Results: Cumulative mean absorbed skin dose (to head/neck/arms) was 55.8 mGy (range 0-1735 mGy). For lifetime cumulative dose, we did not observe an excess radiation-related risk (excess relative risk/Gy=-0.01 (95% CI -0.43 to 0.52). However, we observed that basal cell carcinoma risk was increased for radiation dose received before age 30 (excess relative risk/Gy=0.59, 95% CI -0.11 to 1.42) and before 1960 (excess relative risk/Gy=2.92, 95% CI 1.39 to 4.45)., Conclusions: Basal cell carcinoma risk was unrelated to low-dose radiation exposure among radiologic technologists. Because of uncertainties in dosimetry and sensitivity to model specifications, both our null results and our findings of excess risk for dose received before age 30 and exposure before 1960 should be interpreted with caution., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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., (© 2015 by American Society of Clinical Oncology.)

Objectives: The number of nuclear medicine procedures has increased substantially over the past several decades, with uncertain health risks to the medical workers who perform them. We estimated risks of incidence and mortality from cancer and circulatory disease associated with performing procedures involving the use of radionuclides., Methods: From a nationwide cohort of 90,955 US radiologic technologists who completed a mailed questionnaire during 1994-1998, 22,039 reported ever performing diagnostic radionuclide procedures, brachytherapy, radioactive iodine therapy, or other radionuclide therapy. We calculated multivariable-adjusted HRs and 95% CIs for incidence (through 2003-2005) and mortality (through 2008) associated with performing these procedures., Results: Ever (versus never) performing radionuclide procedures was not associated with risks for most end points examined. However, we observed increased risks for squamous cell carcinoma of the skin (HR=1.29, 95% CI 1.01 to 1.66) with ever performing diagnostic radionuclide procedures, for myocardial infarction incidence (HR=1.37, 95% CI 1.10 to 1.70), all-cause mortality (HR=1.10, 95% CI 1.00 to 1.20) and all-cancer mortality (HR=1.20, 95% CI 1.01 to 1.43) with ever performing brachytherapy, and for mortality from all causes (HR=1.14, 95% CI 1.01 to 1.30), breast cancer (HR=2.68, 95% CI 1.10 to 6.51), and myocardial infarction (HR=1.76, 95% CI 1.02 to 3.04) with ever performing other radionuclide therapy procedures (excluding brachytherapy and radioactive iodine); increasing risks were also observed with greater frequency of performing these procedures, particularly before 1980., Conclusions: The modest health risks among radiologic technologists performing procedures using radionuclides require further examination in studies with individual dose estimates, more detailed information regarding types of procedures performed and radionuclides used, and longer follow-up., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking., Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates., Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer., Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report., (© The Author 2015. Published by Oxford University Press.)

Objectives: There have been few studies of work history and mortality risks in medical radiation workers. We expanded by 11 years and more outcomes our previous study of mortality risks and work history, a proxy for radiation exposure., Methods: Using Cox proportional hazards models, we estimated mortality risks according to questionnaire work history responses from 1983 to 1989 through 2008 by 90,268 US radiological technologists. We controlled for potential confounding by age, birth year, smoking history, body mass index, race and gender., Results: There were 9566 deaths (3329 cancer and 3020 circulatory system diseases). Mortality risks increased significantly with earlier year began working for female breast (p trend=0.01) and stomach cancers (p trend=0.01), ischaemic heart (p trend=0.03) and cerebrovascular diseases (p trend=0.02). The significant trend with earlier year first worked was strongly apparent for breast cancer during baseline through 1997, but not 1998-2008. Risks were similar in the two periods for circulatory diseases. Radiological technologists working ≥5 years before 1950 had elevated mortality from breast cancer (HR=2.05, 95% CI 1.27 to 3.32), leukaemia (HR=2.57, 95% CI 0.96 to 6.68), ischaemic heart disease (HR=1.13, 95% CI 0.96 to 1.33) and cerebrovascular disease (HR=1.28, 95% CI 0.97 to 1.69). No other work history factors were consistently associated with mortality risks from specific cancers or circulatory diseases, or other conditions., Conclusions: Radiological technologists who began working in early periods and for more years before 1950 had increased mortality from a few cancers and some circulatory system diseases, likely reflecting higher occupational radiation exposures in the earlier years., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

In this article, we describe recent methodological enhancements and findings from the dose reconstruction component of a study of health risks among U.S. radiologic technologists. An earlier version of the dosimetry published in 2006 used physical and statistical models, literature-reported exposure measurements for the years before 1960, and archival personnel monitoring badge data from cohort members through 1984. The data and models previously described were used to estimate annual occupational radiation doses for 90,000 radiological technologists, incorporating information about each individual's employment practices based on a baseline survey conducted in the mid-1980s. The dosimetry methods presented here, while using many of the same methods as before, now estimate 2.23 million annual badge doses (personal dose equivalent) for the years 1916-1997 for 110,374 technologists, but with numerous methodological improvements. Every technologist's annual dose is estimated as a probability density function to reflect uncertainty about the true dose. Multiple realizations of the entire cohort distribution were derived to account for shared uncertainties and possible biases in the input data and assumptions used. Major improvements in the dosimetry methods from the earlier version include: A substantial increase in the number of cohort member annual badge dose measurements; Additional information on individual apron usage obtained from surveys conducted in the mid-1990s and mid-2000s; Refined modeling to develop lognormal annual badge dose probability density functions using censored data regression models; Refinements of cohort-based annual badge probability density functions to reflect individual work patterns and practices reported on questionnaires and to more accurately assess minimum detection limits; and Extensive refinements in organ dose conversion coefficients to account for uncertainties in radiographic machine settings for the radiographic techniques employed. For organ dose estimation, we rely on well-researched assumptions about critical exposure-related variables and their changes over the decades, including the peak kilovoltage and filtration typically used in conducting radiographic examinations, and the usual body location for wearing radiation monitoring badges, the latter based on both literature and national recommendations. We have derived organ dose conversion coefficients based on air-kerma weighting of photon fluences from published X-ray spectra and derived energy-dependent transmission factors for protective lead aprons of different thicknesses. Findings are presented on estimated organ doses for 12 organs and tissues: red bone marrow, female breast, thyroid, brain, lung, heart, colon, ovary, testes, skin of trunk, skin of head and neck and arms, and lens of the eye.

Background: UV radiation (UVR) exposure is the primary risk factor for basal cell carcinoma (BCC). Although prescription diuretics have photosensitizing properties, the relationship between diuretic use and BCC remains unclear., Methods: Using data from the United States Radiologic Technologists Study, a large, nationwide prospective cohort, we assessed the relationship between diuretic use and first primary BCC while accounting for sun exposure history, constitutional characteristics, lifestyle factors, and anthropometric measurements for geographically dispersed individuals exposed to a wide range of ambient UVR., Results: After adjustment for potential confounders, we found a significantly increased risk of BCC associated with diuretic use [HR, 1.22; 95% confidence interval (CI), 1.07-1.38]. This relationship was modified by body mass index (P = 0.019), such that BCC risk was increased with diuretic use in overweight (HR, 1.43; 95% CI, 1.16-1.76) and obese individuals (HR, 1.43; 95% CI, 1.09-1.88), but not in normal weight individuals (HR, 0.99; 95% CI, 0.81-1.21)., Conclusions: Increased risk of BCC associated with diuretic use in overweight and obese participants may be related to higher dosages, longer duration of medication use, reduced drug metabolism, or drug interactions., Impact: Future cohort studies should obtain more detailed information on medication use, consider factors that affect drug metabolism, and measure intermediate endpoints such as photosensitivity reactions., (©2014 American Association for Cancer Research.)

Chromosome translocations are a well-recognized biological marker of radiation exposure and cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be detected, and whether there is temporal decay of induced translocations in radiation-exposed populations. Dosimetric uncertainties can substantially alter the shape of dose-response relationships; although regression-calibration methods have been used in some datasets, these have not been applied in radio-occupational studies, where there are also complex patterns of shared and unshared errors that these methods do not account for. In this article we evaluated the relationship between estimated occupational ionizing radiation doses and chromosome translocation rates using fluorescent in situ hybridization in 238 U.S. radiologic technologists selected from a large cohort. Estimated cumulative red bone marrow doses (mean 29.3 mGy, range 0-135.7 mGy) were based on available badge-dose measurement data and on questionnaire-reported work history factors. Dosimetric assessment uncertainties were evaluated using regression calibration, Bayesian and Monte Carlo maximum likelihood methods, taking account of shared and unshared error and adjusted for overdispersion. There was a significant dose response for estimated occupational radiation exposure, adjusted for questionnaire-based personal diagnostic radiation, age, sex and study group (5.7 translocations per 100 whole genome cell equivalents per Gy, 95% CI 0.2, 11.3, P = 0.0440). A significant increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. For combined estimated occupational and personal-diagnostic-medical radiation exposures, there was a borderline-significant modifying effect of age (P = 0.0704), but little evidence (P > 0.5) of temporal decay of induced translocations. The three methods of analysis to adjust for dose uncertainty gave similar results. In summary, chromosome translocation dose-response slopes were detectable down to <100 mGy and were compatible with those observed in other radiation-exposed populations. However, there are substantial uncertainties in both occupational and other (personal-diagnostic-medical) doses that may be imperfectly taken into account in our analysis.

Although diagnostic x-ray procedures provide important medical benefits, cancer risks associated with their exposure are also possible, but not well characterized. The US Radiologic Technologists Study (1983-2006) is a nationwide, prospective cohort study with extensive questionnaire data on history of personal diagnostic imaging procedures collected prior to cancer diagnosis. We used Cox proportional hazard regressions to estimate thyroid cancer risks related to the number and type of selected procedures. We assessed potential modifying effects of age and calendar year of the first x-ray procedure in each category of procedures. Incident thyroid cancers (n = 251) were diagnosed among 75,494 technologists (1.3 million person-years; mean follow-up = 17 years). Overall, there was no clear evidence of thyroid cancer risk associated with diagnostic x-rays except for dental x-rays. We observed a 13% increase in thyroid cancer risk for every 10 reported dental radiographs (hazard ratio = 1.13, 95% confidence interval: 1.01, 1.26), which was driven by dental x-rays first received before 1970, but we found no evidence that the relationship between dental x-rays and thyroid cancer was associated with childhood or adolescent exposures as would have been anticipated. The lack of association of thyroid cancer with x-ray procedures that expose the thyroid to higher radiation doses than do dental x-rays underscores the need to conduct a detailed radiation exposure assessment to enable quantitative evaluation of risk.

Background/aim: Geographic gradients in breast cancer incidence and mortality suggest that vitamin D may reduce risk. The enzyme 25-hydroxyvitamin D 24-hydroxylase (CYP24A1), which degrades the active form of vitamin D, and the vitamin D receptor (VDR) are both found in breast tissue. We investigated six polymorphisms in CYP24A1 and two in the VDR gene in association with breast cancer risk., Materials and Methods: We conducted a case-control study within the nationwide U.S. Radiologic Technologists cohort, including 845 controls and 484 incident breast cancer cases. Associations of polymorphic variants and ecologic and personal measures of sun exposure with breast cancer risk were assessed using unconditional logistic regression., Results: Two polymorphisms in CYP24A1 were associated with increased breast cancer risk (rs34043203, P(trend)=0.03; rs2762934, P(trend)=0.005) and one with reduced breast cancer risk (rs1570669, P(trend)=0.048). Risk was inversely associated with minor alleles for the VDR Bsm1 polymorphism (rs1544410, P(trend)=0.05) but not Fok1 (rs2228570). Sunlight measures were not associated with breast cancer risk, however significant interactions between time outdoors in the teen years and three unlinked genotypes were found for VDR (rs1544410, rs2228570) and CYP24A1 (rs1570669)., Conclusion: In this nation-wide breast cancer case-control study, we found that the vitamin D pathway was involved in disease etiology and our results further suggest that reduced cancer risk, in association with sunlight, may depend on timing of exposure and genetic background. These findings merit further investigation.

Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n = 842), blacks (n = 646), and people of other races/ethnicities (n = 12). Participants were recruited monthly (2008-2009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25% of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest.

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors., Competing Interests: The authors have declared that no competing interests exist.

Basal cell carcinoma (BCC) is the most common cancer in Caucasian populations. Although several risk factors are well-established, including ultraviolet radiation (UVR) sensitivity and exposure, few studies have examined anthropometric measures and BCC. Using Cox proportional hazards regression analysis, we prospectively investigated the relationship between height, weight and body mass index (BMI) and BCC in 58,213 Caucasian participants (11,631 men and 46,582 women) from the United States Radiological Technologists cohort. This analysis was limited to participants who were cancer-free at baseline. The baseline questionnaire provided self-reported anthropometric factors and the subsequent questionnaire collected skin cancer susceptibility factors, lifetime UVR exposure derived from residential and personal UVR exposure (time outdoors) and health outcomes. During 509,465 person-years of follow-up, we identified 2,291 BCC cases (486 men; 1,805 women). BCC risk increased with increasing height, and decreased with increasing weight and BMI in both sexes, even after adjusting for UVR susceptibility factors and exposures. For BMI categories: <25 (reference); 25-<30; 30-<35 and ≥ 35 kg m(-2) , multivariate hazard ratios (HR) in women were: 1.00; 0.74 (95% CI = 0.66-0.83); 0.67 (0.56-0.81) and 0.57 (0.44-0.74), respectively, p-trend ≤ 0.0001. Risks were similar in men. The inverse association between BMI and BCC was unaffected by controlling for sun-related exposures. Nevertheless, it may at least partly reflect residual UVR confounding. Further research with more detailed sun exposure data, including clothing patterns, would help clarify the relationship between BMI and BCC., (Copyright © 2011 UICC.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of colorectal and other cancers, but the association with basal cell carcinoma (BCC) is unclear. Previous epidemiological studies have been small in size, conducted in especially vulnerable populations, or have not accounted for solar ultraviolet exposure, a major risk factor for BCC. In the United States Radiologic Technologists cohort, we followed subjects to assess NSAID use on risk of first incident BCC. We included Caucasian participants who responded to both second and third questionnaires (administered from 1994 to 1998 and 2003 to 2005, respectively), and who reported no cancer at the time of the second questionnaire, N = 58,213. BCC, constituent risk factors (e.g., eye color, complexion, hair color) and sun exposure history were assessed through self-administered survey. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Of the 58,213 people in the study population, 2,291 went on to develop BCC. Any NSAID use was not associated with subsequent incidence of BCC (HR = 1.04, 95% CI: 0.92-1.16) after adjusting for age, sex and estimated lifetime summer sun exposure. Neither association was observed when stratified by NSAID type (aspirin and other NSAIDs), nor did dose-response patterns emerge by frequency of use (average days per month). Further analyses did not reveal interaction with sex, birth cohort, smoking, alcohol consumption, sun exposure, occupational radiation exposure or personal risk factors for BCC. In this large nationwide study, we observed no association between NSAID use and subsequent BCC risk., (Copyright © 2011 UICC.)

Relationships are unclear between polymorphisms in genes involved in metabolism and detoxification of various chemicals and papillary thyroid cancer (PTC) risk as well as their potential modification by alcohol or tobacco intake. We evaluated associations between 1647 tagging single nucleotide polymorphisms (SNPs) in 132 candidate genes/regions involved in metabolism of exogenous and endogenous compounds (Phase I/II, oxidative stress, and metal binding pathways) and PTC risk in 344 PTC cases and 452 controls. For 15 selected regions and their respective SNPs, we also assessed interaction with alcohol and tobacco use. Logistic regression models were used to evaluate the main effect of SNPs (P(trend)) and interaction with alcohol/tobacco intake. Gene- and pathway-level associations and interactions (P(gene interaction)) were evaluated by combining P(trend) values using the adaptive rank-truncated product method. While we found associations between PTC risk and nine SNPs (P(trend) ≤ 0.01) and seven genes/regions (P(region)<0.05), none remained significant after correction for the false discovery rate. We found a significant interaction between UGT2B7 and NAT1 genes and alcohol intake (P(gene interaction)=0.01 and 0.02 respectively) and between the CYP26B1 gene and tobacco intake (P(gene interaction)=0.02). Our results are suggestive of interaction between the genetic polymorphisms in several detoxification genes and alcohol or tobacco intake on risk of PTC. Larger studies with improved exposure assessment should address potential modification of PTC risk by alcohol and tobacco intake to confirm or refute our findings.

Background: The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer., Methods: The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC)., Results: The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10(-4), minor allele frequency (MAF)=0.23). This SNP yielded an OR(rec) of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-OR(rec) of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01)., Conclusions: These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.

Nulliparity is an established breast cancer risk factor, particularly when compared with parity at young ages. The authors aggregated data from 4 US prospective studies (1979-2006) including 32,641 nulliparous (1,612 breast cancers) and 204,270 parous (8,180 breast cancers) women to examine the hypothesis that nulliparity may increase susceptibility to established postmenopausal breast cancer risk factors. The aggregated hazard ratio for nulliparous versus all parous women = 1.27 (95% confidence interval: 1.21, 1.34), and that for nulliparous versus women <25 years of age at first birth = 1.38 (95% confidence interval: 1.30, 1.46). Among nulliparous women, the hazard ratios for current menopausal hormone therapy use (vs. never use), body mass index ≥30 kg/m(2) (vs. <25 kg/m(2)), and weekly consumption of ≥7 alcoholic drinks (vs. none) ranged from 1.3 to 1.6. The hazard ratios did not differ by parity. In a model including all women, the joint association for each of these factors and nulliparity combined compared with first birth before age 25 years was an approximately 2-fold increased breast cancer risk. Although the baseline risk is higher for nulliparous women compared with parous women, these results suggest that the associations between hormone-related factors and breast cancer do not differ by parity.

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.

Objective: Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk., Methods: We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose-response across genotypes., Results: There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2-12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0-3.8) and EOR/Gy < 0 (95%CI < 0-14.8) for the GC and CC genotypes, respectively, (p (interaction) = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined., Conclusions: This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.

We studied cancer mortality in a cohort of 5,573 women with scoliosis and other spine disorders who were diagnosed between 1912 and 1965 and were exposed to frequent diagnostic X-ray procedures. Patients were identified from medical records in 14 orthopedic medical centers in the United States and followed for vital status and address through December 31, 2004, using publicly available regional, state and nationwide databases. Causes of death were obtained from death certificates or through linkage with the National Death Index (NDI). Statistical analyses included standardized mortality ratios (SMR = observed/expected) based on death rates for U.S. females and internal comparisons using Cox regression models with attained age as the time scale. Diagnostic radiation exposure was estimated from radiology files for over 137,000 procedures; estimated average cumulative radiation doses to the breast, lung, thyroid and bone marrow were 10.9, 4.1, 7.4 and 1.0 cGy, respectively. After a median follow-up period of 47 years, 1527 women died, including 355 from cancer. Cancer mortality was 8% higher than expected (95% CI = 0.97-1.20). Mortality from breast cancer was significantly elevated (SMR = 1.68; 95% CI: 1.38-2.02), whereas death rates from several other cancers were below expectation, in particular lung (SMR = 0.77), cervical (SMR = 0.31), and liver (SMR = 0.17). The excess relative risk (ERR) for breast cancer mortality increased significantly with 10-year lagged radiation dose to the breast (ERR/Gy = 3.9; 95% CI: 1.0-9.3).

Abstract In this paper, we describe recent methodological enhancements and findings from the dose reconstruction component of a study of cancer risks among U.S. radiologic technologists. An earlier version of the dosimetry published in 2006 (Simon et al., Radiat. Res. 166, 174-192, 2006) used physical and statistical models, literature-reported exposure measurements for the years before 1960, and archival personnel monitoring badge data from cohort members through 1984. The data and models were used to estimate unknown occupational radiation doses for 90,000 radiological technologists, incorporating information about each individual's employment practices based on a survey conducted in the mid-1980s. The dosimetry methods presented here, while using many of the same methods as before, now estimate annual and cumulative occupational badge doses (personal dose equivalent) to about 110,000 technologists for each year worked from 1916 to 2006, but with numerous methodological improvements. This dosimetry, using much more comprehensive information on individual use of protection aprons, estimates radiation absorbed doses to 12 organs and tissues (red bone marrow, ovary, colon, brain, lung, heart, female breast, skin of trunk, skin of head and neck and arms, testes, thyroid and lens of the eye). Every technologist's annual dose is estimated as a probability density function (pdf) to account for shared and unshared uncertainties. Major improvements in the dosimetry methods include a substantial increase in the number of cohort member annual badge dose measurements, additional information on individual apron use obtained from surveys conducted in the 1990s and 2005, refined modeling to develop annual badge dose pdfs using Tobit regression, refinements of cohort-based annual badge pdfs to delineate exposures of highly and minimally exposed individuals and to assess minimal detectable limits more accurately, and extensive refinements in organ dose conversion coefficients to account for uncertainties in radiographic techniques employed. For organ dose estimation, we rely on well-researched assumptions about critical exposure-related variables and their changes over the decades, including the peak kilovoltage and filtration typically used in conducting radiographic examinations and the usual body location for wearing radiation monitoring badges. We have derived organ dose conversion coefficients based on air-kerma weighting of photon fluences from published X-ray spectra and derived energy-dependent transmission factors for protective aprons of different thicknesses. We tailor bone marrow dose estimates to individual cohort members by using an individual-specific body mass index correction factor. To our knowledge the models and reconstructed doses presented herein represent the most comprehensive dose reconstructions undertaken for a cohort of medical radiation workers.