Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Prediagnostic serum concentrations of per- and polyfluoroalkyl substances and risk of papillary thyroid cancer in the Finnish Maternity Cohort.

Human exposure to per- and polyfluoroalkyl substances (PFAS) occurs globally through contaminated food, dust, and drinking water. Studies of PFAS and thyroid cancer have been limited. We conducted a nested case-control study of prediagnostic serum levels of 19 PFAS and papillary thyroid cancer (400 cases, 400 controls) in the Finnish Maternity Cohort (pregnancies 1986-2010; follow-up through 2016), individually matched on sample year and age. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for log2 transformed and categorical exposures, overall and stratified by calendar period, birth cohort, and median age at diagnosis. We adjusted for other PFAS with Spearman correlation rho = 0.3-0.6. Seven PFAS, including perfluoroctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), N-ethyl-perfluorooctane sulfonamidoacetic acid (EtFOSAA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonic acid (PFHxS) were detected in >50% of women. These PFAS were not associated with risk of thyroid cancer, except for PFHxS, which was inversely associated (OR log2 = 0.82, 95% CI: 0.70-0.97). We observed suggestive but imprecise increased risks associated with PFOA, PFOS, and EtFOSAA for those diagnosed at ages <40 years, whereas associations were null or inverse among those diagnosed at 40+ years (P-interaction: .02, .08, .13, respectively). There was little evidence of other interactions. These results show no clear association between PFAS and papillary thyroid cancer risk. Future work would benefit from evaluation of these relationships among those with higher exposure levels and during periods of early development when the thyroid gland may be more susceptible to environmental harms.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

Occupational Radiation Dose Trends in U.S. Radiologic Technologists Assisting with Fluoroscopically Guided Interventional Procedures, 1980-2020.

PURPOSE: To summarize dose trends from 1980 to 2020 for 19,651 U.S. Radiologic Technologists who reported assisting with fluoroscopically guided interventional procedures (FGIPs), overall and by work history characteristics. MATERIALS AND METHODS: A total of 762,310 annual personal dose equivalents at a 10-mm reference depth (doses) during 1980-2020 for 43,823 participants of the U.S. Radiologic Technologists (USRT) cohort who responded to work history questionnaires administered during 2012-2014 were summarized. This population included 19,651 technologists who reported assisting with FGIP (≥1 time per month for ≥12 consecutive months) at any time during the study period. Doses corresponding to assistance with FGIP were estimated in terms of proximity to patients, monthly procedure frequency, and procedure type. Box plots and summary statistics (eg, medians and percentiles) were used to describe annual doses and dose trends. RESULTS: Median annual dose corresponding to assistance with FGIP was 0.65 mSv (interquartile range [IQR], 0.60-1.40 mSv; 95th percentile, 6.80). Higher occupational doses with wider variability were associated with close proximity to patients during assistance with FGIP (median, 1.20 mSv [IQR, 0.60-4.18 mSv]; 95th percentile, 12.66), performing ≥20 FGIPs per month (median, 0.75 mSv [IQR, 0.60-2.40 mSv]; 95th percentile, 9.44), and assisting with high-dose FGIP (median, 0.70 mSv [IQR, 0.60-1.90 mSv]; 95th percentile, 8.30). CONCLUSIONS: Occupational doses corresponding to assistance with FGIP were generally low but varied with exposure frequency, procedure type, and proximity to patients. These results highlight the need for vigilant dose monitoring, radiation safety training, and proper protective equipment.

Absorbed dose coefficients for pediatric differentiated thyroid cancer patients undergoing radioiodine therapy.

The escalating incidence of differentiated thyroid cancer (DTC) in pediatric patients and the resultant growing use of radioactive iodine (RAI) reinforce the need to evaluate radiation exposure to normal tissues and radiation-induced health risks in pediatric patients undergoing RAI therapy. In the current study, we calculated absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq-1) specific for pediatric patients with localized DTC undergoing RAI therapy following total thyroidectomy for use in epidemiological studies. We first modified previously-published biokinetic models for adult thyroid cancer patients to achieve a reasonable agreement with iodine biokinetics observed in pediatric patients or design principles addressed in the International Commission on Radiological Protection (ICRP) reference age-specific biokinetic models. We then combined the biokinetic models in conjunction withSvalues derived from ICRP reference pediatric voxel phantoms. The absorbed dose coefficients for pediatric patients were overall greater than those for adults with a ratio (pediatric/adult) up to 11.6 and rapidly decreased with increasing age. The sensitivity analysis showed that the renal clearance rate andSvalues may have the greatest impact on the absorbed dose coefficients with the rank correlation coefficients ranging from -0.53 to -0.82 (negative correlations) and from 0.51 to 0.80 (positive correlations), respectively. The results of the current study may be utilized in clinical or epidemiological studies to estimate organ-specific radiation absorbed doses and radiation-associated health risks among pediatric thyroid cancer patients.

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018).

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.

Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

Anthropometric, dietary, and lifestyle factors and risk of advanced thyroid cancer: The NIH-AARP diet and health cohort study.

BACKGROUND: Most patients diagnosed with thyroid cancer have low-risk disease, but some have a higher risk for persistent or recurrent disease and even death from thyroid cancer. Few studies have evaluated potential anthropometric, lifestyle, or dietary risk factors for advanced or aggressive types of thyroid cancer. METHODS: Using data from a large US cohort study, we examined associations for high-risk thyroid cancer (HRTC) and, separately, low-risk thyroid cancer (LRTC) in relation to anthropometric factors, diet, smoking, and alcohol consumption. The National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study included 304,122 participants (124,656 women and 179,466 men) without a history of cancer who completed a mailed questionnaire in 1996-1997 and were followed for cancer incidence through 2011 via linkages with state cancer registries. Hazard ratios (HRs) for anthropometric, dietary, and lifestyle factors in relation to HRTC or LRTC, defined using guidance from the American Thyroid Association initial risk of recurrence classification, were calculated using multivariable-adjusted Cox proportional hazards regression models. RESULTS: During follow-up (median = 10.1 years), 426 participants were diagnosed with HRTC (n = 95) or LRTC (n = 331). In models combining men and women, baseline waist circumference (per 5 cm, HR = 1.13, 95% confidence interval [CI] 1.01-1.27) and weight gain from age 18 years to baseline age (per 5 kg, HR = 1.14, 95% CI 1.02-1.28) were positively associated with risk of HRTC but not LRTC. In contrast, vegetable intake (per cup equivalents/day, HR = 1.15, 95% CI 1.01-1.30), cigarette smoking (current vs. never, HR = 0.39, 95% CI 0.23-0.68), and alcohol consumption (per drink/day, HR = 0.83, 95% CI 0.70-0.97) were associated with risk of LRTC but not HRTC. The association of LRTC risk with vegetable intake was limited to men, and that of current smoking was more pronounced in women. CONCLUSIONS: Our findings suggest that greater waist circumference and adulthood weight gain are associated with thyroid cancers at higher risk for recurrence. These results may have implications for the primary prevention of advanced thyroid cancer.

Absolute and relative risk estimation in the presence of outcome ascertainment gaps and competing risks.

Incomplete coverage by cancer registries can lead to an underreporting of cancers and a resulting bias in risk estimates. When registries are defined by geographic region, gaps in observation can arise for individuals who reside outside of or migrate from the total registry catchment area. Moreover, the exact periods of non-observation for an individual may be unknown due to intermittent reporting of residential histories. The motivating example for this work is the U.S. Radiologic Technologist (USRT) study which ascertained cancer outcomes for a national cohort through 43 state/regional registries; similar gaps in outcome ascertainment can appear in other registry or electronic health record- based cohort studies. We propose a two-step procedure for estimating relative and absolute risk in these settings. First, using a mover stayer model fitted to individuals' known residential history, we obtain individual posterior probabilities of residing outside the registry catchment area each year. Second, we incorporate these probabilities in the survival data likelihood for competing risks to account for unobserved events. We assess the performance of the proposed method in extensive simulation studies. Compared to several simple alternative approaches, the proposed method reduces bias and improves efficiency. Finally, we apply the proposed method to a study of first primary lung cancers in the USRT cohort.

Absorbed dose coefficients for adult thyroid cancer patients undergoing radioiodine therapy.

Use of radioactive iodine (RAI) for thyroid cancer patients is accompanied by elevated risks of radiation-induced adverse effects due to significant radiation exposure of normal tissues or organs other than the thyroid. The health risk estimation for thyroid cancer patients should thus be preceded by estimating normal tissue doses. Although organ dose estimation for a large cohort often relies on absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq-1) based on population models, no data are available for thyroid cancer patients. In the current study, we calculated absorbed dose coefficients specific for adult thyroid cancer patients undergoing RAI treatment after recombinant human TSH (rhTSH) administration or thyroid hormone withdrawal (THW). We first adjusted the transfer rates in the biokinetic model previously developed for THW patients for use in rhTSH patients. We then implemented the biokinetic models for thyroid cancer patients coupled withSvalues from the International Commission on Radiological Protection (ICRP) reference voxel phantoms to calculate absorbed dose coefficients. The biokinetic model for rhTSH patients predicted the extrathyroidal iodine decreasing noticeably faster than in the model for THW patients (calculated half-times of 12 and 15 h for rhTSH administration and THW, respectively). All dose coefficients for rhTSH patients were lower than those for THW patients with the ratio (rhTSH administration/THW) ranging from 0.60 to 0.95 (mean = 0.67). The ratio of the absorbed dose coefficients in the current study to the ICRP dose coefficients, which were derived from models for normal subjects, varied widely from 0.21 to 7.19, stressing the importance of using the dose coefficients for thyroid cancer patients. The results of this study will provide medical physicists and dosimetrists with scientific evidence to protect patients from excess exposure or to assess radiation-induced health risks caused by RAI treatment.

Ascertainment of Incident Cancer by US Population-Based Cancer Registries Versus Self-Reports and Death Certificates in a Nationwide Cohort Study, the US Radiologic Technologists Study.

Follow-up of US cohort members for incident cancer is time-consuming, is costly, and often results in underascertainment when the traditional methods of self-reporting and/or medical record validation are used. We conducted one of the first large-scale investigations to assess the feasibility, methods, and benefits of linking participants in the US Radiologic Technologists (USRT) Study (n = 146,022) with the majority of US state or regional cancer registries. Follow-up of this cohort has relied primarily on questionnaires (mailed approximately every 10 years) and linkage with the National Death Index. We compared the level of agreement and completeness of questionnaire/death-certificate-based information with that of registry-based (43 registries) incident cancer follow-up in the USRT cohort. Using registry-identified first primary cancers from 1999-2012 as the gold standard, the overall sensitivity was 46.5% for self-reports only and 63.0% for both self-reports and death certificates. Among the 37.0% false-negative reports, 27.8% were due to dropout, while 9.2% were due to misreporting. The USRT cancer reporting patterns differed by cancer type. Our study indicates that linkage to state cancer registries would greatly improve completeness and accuracy of cancer follow-up in comparison with questionnaire self-reporting. These findings support ongoing development of a national US virtual pooled registry with which to streamline cohort linkages.

Reproductive factors, hormone use, and incidence of melanoma in a cohort of US Radiologic Technologists.

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 <12 years vs ≥14 years: RR = 1.48, 95% CI = 1.11-1.98; 1.19, 0.89-1.61; 1.26, 0.93-1.73), and in women with older age at first birth (25-29 and ≥30 years vs <25 years; 1.09, 0.86-1.39; 1.48, 1.12-1.95; P-value for trend = 0.006). However, no significant association was observed for other reproductive factors, and for all exogenous hormone use. The associations of melanoma incidence for most reproductive factors and exogenous hormone use were not modified by ambient UVR, eye color, natural hair color at age 15 and skin complexion. The exception was that natural hair color at age 15 modified the associations of melanoma for age at menarche (P-value for interaction = 0.004) and age at first birth among parous women (0.005). In participants with blonde/red/auburn natural hair color at age 15, we found increased risk of melanoma among women who experienced menarche at age 13, 12 and <12 years (vs ≥14 years: RR = 3.54, 95% CI = 1.98-6.90; 2.51, 1.37-4.98; 2.66, 1.41-5.36, respectively; P-value for trend = 0.10). However, the association between age at menarche and melanoma was null in participants with brown/black natural hair color at age 15. 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.

Collar Badge Lens Dose Equivalent Values among United States Physicians Performing Fluoroscopically Guided Interventional Procedures.

PURPOSE: To describe the range of occupational badge dose readings and annualized dose records among physicians performing fluoroscopically guided interventional (FGI) procedures using job title information provided by the same 3 major medical institutions in 2009, 2012, and 2015. MATERIALS AND METHODS: The Radiation Safety Office of selected hospitals was contacted to request assistance with identifying physicians in a large commercial dosimetry database. All entries judged to be uninformative of occupational doses to FGI procedure staff were excluded. Monthly and annualized doses were described with univariate statistics and box-and-whisker plots. RESULTS: The dosimetry data set of interventional radiology staff contained 169 annual dose records from 77 different physicians and 698 annual dose records from 455 nonphysicians. The median annualized lens dose equivalent values among physicians (11.9 mSv; interquartile range [IQR], 6.9-20.0 mSv) was nearly 3-fold higher than those among nonphysician medical staff assisting with FGI procedures (4.0 mSv; IQR, 1.8-6.7 mSv) (P < .001). During the study period, without eye protection, 25% (23 of 93) of the physician annualized lens dose equivalent values may have exceeded 20 mSv; for nonphysician medical staff, this value may have been exceeded 3.5% (6 of 173) of the time. However, these values did not account for eye protection. CONCLUSIONS: The findings from this study highlight the importance of mitigating occupational dose to the eyes of medical staff, particularly physicians, performing or assisting with FGI procedures. Training on radiation protection principles, the use of personal protective equipment, and patient radiation dose management can all help ensure that the occupational radiation dose is adequately controlled.

Associations between artificial light at night and risk for thyroid cancer: A large US cohort study.

BACKGROUND: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. METHODS: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. RESULTS: Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18-2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26-2.60) than men (HR, 1.29; 95% CI, 0.86-1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. CONCLUSIONS: LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms.

Trends in Occupational Radiation Doses for U.S. Radiologic Technologists Performing General Radiologic and Nuclear Medicine Procedures, 1980-2015.

Background Occupational doses to most medical radiation workers have declined substantially since the 1950s because of improvements in radiation protection practices. However, different patterns may have emerged for radiologic technologists working with nuclear medicine because of the higher per-procedure doses and increasing workloads. Purpose To summarize annual occupational doses during a 36-year period for a large cohort of U.S. radiologic technologists and to compare dose between general radiologic technologists and those specializing in nuclear medicine procedures. Materials and Methods Annual personal dose equivalents (referred to as doses) from 1980 to 2015 were summarized for 58 434 (62%) participants in the U.S. Radiologic Technologists (USRT) cohort who responded to the most recent mailed work history survey (years 2012-2014) and reported never regularly performing interventional procedures. Doses were partitioned according to the performance of nuclear medicine (yes or no, frequency, procedure type) by calendar year. Annual dose records were described by using summary statistics (eg, median and 25th and 75th percentiles). Results Median annual doses related to performance of general radiologic procedures decreased from 0.60 mSv (interquartile range [IQR], 0.10-1.9 mSv) in 1980 to levels below the limits of detection by 2015, whereas annual doses related to performance of nuclear medicine procedures remained relatively high during this period (median, 1.2 mSv; IQR, 0.12-3.0 mSv). Higher median annual doses were associated with more frequent (above vs below the median) performance of diagnostic nuclear medicine procedures (≥35 vs <35 times per week; 1.6 mSv [IQR, 0.30-3.3 mSv] and 0.9 mSv [IQR, 0.10-2.6 mSv]). Higher and more variable annual doses were associated with more frequent performance of cardiac nuclear medicine (≥10 times per week) and PET (nine or more times per week) examinations (median, 1.6 mSv [IQR, 0.30-2.2 mSv] and 2.2 mSv [IQR, 0.10-4.6 mSv], respectively). Conclusion Annual doses to U.S. radiologic technologists performing general radiologic procedures declined during a 36-year period. However, consistently higher and more variable doses were associated with the performance of nuclear medicine procedures, particularly cardiac nuclear medicine and PET procedures. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mettler and Guiberteau in this issue.

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women.

BACKGROUND AND AIMS: In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with LC risk, overall and by histology, by leveraging resources from five prospective cohorts. APPROACH AND RESULTS: Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC cases (HCC, n = 83; ICC, n = 56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one-unit increase in log2 hormone value (approximate doubling of circulating concentration) and LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas SHBG was associated with a 31% increased risk (OR = 1.31; 95% CI = 1.05-1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR = 1.40; 95% CI = 1.05-1.89), but not HCC (OR = 1.12; 95% CI = 0.81-1.54). CONCLUSIONS: This study provides evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.

Lung cancer mortality associated with protracted low-dose occupational radiation exposures and smoking behaviors in U.S. radiologic technologists, 1983-2012.

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.

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.

Abdominal and gluteofemoral size and risk of liver cancer: The liver cancer pooling project.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to <25 kg/m2 ; HR = 1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR = 1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR = 0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements.