Cumulative Radiation Exposure and Lifetime Cancer Risk in Patients With Tetralogy of Fallot Requiring Early Intervention.

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, utilizing either a staged repair (SR) or primary repair (PR) approach. They are exposed to several sources of low-dose ionizing radiation, which may contribute to increased cancer risk. Objectives: The purpose of this study was to compare cumulative radiation exposure and associated lifetime attributable risk (LAR) of cancer between treatment strategies in sTOF. Methods: Neonates with sTOF who underwent SR or PR from 2012 to 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Radiation exposure from all radiologic studies prior to 18 months of age was converted to organ-equivalent doses and projected LAR of cancer incidence using the National Cancer Institute dosimetry tools. Results: There were 242 neonates from 8 centers, including patients with 146 SR and 96 PR. Cumulative total effective dose was significantly higher for SR (median 8.3 mSv, IQR: 3.0-17.4 mSv) than PR (2.1 mSv, IQR: 0.8-8.5 mSv; P < 0.001). Cumulative organ-level doses were significantly higher in SR compared to PR. Regardless of treatment strategy, LARs were higher in females compared to males. Among organs with median exposure >1 mGy in females, the LAR was highest for breast in SR (mean 1.9/1,000 patients). The highest proportion of cancers attributable to radiation exposure was projected for thyroid cancer in females undergoing SR (7.3%). Conclusions: Cumulative radiation exposure and LARs were higher among those undergoing SR compared to PR. This will be an important factor to consider in determining the preferred neonatal treatment strategy and should substantiate efforts to reduce radiation exposure in this vulnerable population.

Ambient ultraviolet A, ultraviolet B and risk of melanoma in a nationwide United States cohort, 1984-2014.

BACKGROUND: Ultraviolet radiation (UVR) exposure is the primary risk factor for melanoma although the relationship is complex. Compared to radiation from UVB wavelengths, UVA makes up a majority of the surface solar UVR, penetrates the skin more deeply, is the principal range emitted by tanning beds, and is less filtered by sunscreens and window glass. Few studies have examined the relationship between ambient UVA and UVB and melanoma risk. METHODS: Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for the association between satellite-based ambient (based on residential history) UVA, UVB and melanoma in non-Hispanic White participants using data from the United States Radiologic Technologists study, a large, nationwide prospective cohort. Associations of UVA and UVB quartile (Q) were examined in mutually adjusted and stratified models, additionally adjusted for demographic and sun sensitivity characteristics. RESULTS: There were 837 incident melanoma cases among 62,785 participants. Incidence of melanoma was statistically significantly increased for the highest quartile of childhood UVA exposure after adjustment for UVB (IRR = 2.82; 95%CI:1.46,5.44), but not for higher childhood UVB after adjustment for UVA. Childhood UVA was associated with increased melanoma risk within strata of UVB. Childhood UVB was not associated with melanoma after adjustment for UVA, but there was some evidence of lower risk with increased lifetime ambient UVB after UVA adjustment. CONCLUSIONS: Melanoma risk was elevated among participants living in locations with high annual childhood and lifetime UVA after controlling for UVB. With confirmation, these findings support increased protection from solar UVA for melanoma prevention.

Enhanced Internal Dosimetry for Alimentary Tract Organs in Nuclear Medicine based on the ICRP Mesh-Type Reference Phantoms.

This study introduces a refined approach for more accurately estimating radiation doses to alimentary tract organs in nuclear medicine, by utilizing the ICRP pediatric and adult mesh-type reference computational phantoms (MRCPs) that improved the anatomical representation of these organs. Our initial step involved compiling a comprehensive dataset of electron Specific Absorbed Fractions (SAFs) for all source-target pairs of alimentary tract organs in both adult and pediatric phantoms, calculating SAFs for all cases in the present study only except those computed in the previous study for certain pediatric phantom cases. Subsequently, we determined S values for 1,252 radionuclides, facilitating dosimetry applications. The consistency of target and source masses for alimentary tract organs in the MRCPs with the reference values in ICRP Publication 89 led to noticeable differences in SAF, S values, and consequently, absorbed dose coefficients when compared to the stylized models in ICRP Publication 100. Notably, the S value ratios (MRCP/stylized) for selected radionuclides-11C, 18F, 68Ga, and 131I-ranged from 0.41 to 7.60. Particularly for therapeutic 131I-iodide in thyroid cancer, the use of MRCPs resulted in up to 1.49 times higher absorbed dose coefficients for the colon than those derived from stylized models, while the stomach dose coefficients decreased by a factor of 0.72. The application of our findings promises enhanced, more realistic dosimetry for alimentary tract organs, especially beneficial for radiopharmaceuticals likely to accumulate within these organs.

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.

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.

BMI and breast cancer risk around age at menopause.

BACKGROUND: A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.

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.

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.

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.

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Association of hormonal and reproductive factors with differentiated thyroid cancer risk in women: a pooled prospective cohort analysis.

BACKGROUND: The incidence of differentiated thyroid cancer (DTC) is higher in women than in men but whether sex steroid hormones contribute to this difference remains unclear. Studies of reproductive and hormonal factors and thyroid cancer risk have provided inconsistent results. METHODS: Original data from 1 252 907 women in 16 cohorts in North America, Europe, Australia and Asia were combined to evaluate associations of DTC risk with reproductive and hormonal factors. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During follow-up, 2142 women were diagnosed with DTC. Factors associated with higher risk of DTC included younger age at menarche (<10 vs 10-11 years; HR, 1.28; 95% CI, 1.00-1.64), younger (<40; HR, 1.31; 95% CI, 1.05-1.62) and older (≥55; HR, 1.33; 95% CI, 1.05-1.68) ages at menopause (vs 40-44 years), ever use of menopausal hormone therapy (HR, 1.16; 95% CI, 1.02-1.33) and previous hysterectomy (HR, 1.25; 95% CI, 1.13-1.39) or bilateral oophorectomy (HR, 1.14; 95% CI, 1.00-1.29). Factors associated with lower risk included longer-term use (≥5 vs <5 years) of oral contraceptives (HR, 0.86; 95% CI, 0.76-0.96) among those who ever used oral contraception and baseline post-menopausal status (HR, 0.82; 95% CI, 0.70-0.96). No associations were observed for parity, duration of menopausal hormone therapy use or lifetime number of reproductive years or ovulatory cycles. CONCLUSIONS: Our study provides some evidence linking reproductive and hormonal factors with risk of DTC. Results should be interpreted cautiously considering the modest strength of the associations and potential for exposure misclassification and detection bias. Prospective studies of pre-diagnostic circulating sex steroid hormone measurements and DTC risk may provide additional insight.

All-Cause and Cause-Specific Mortality Among Low-Risk Differentiated Thyroid Cancer Survivors in the United States.

Background: Despite the excellent disease-specific survival associated with low-risk differentiated thyroid cancer (DTC), its diagnosis and management have been linked to patient concerns about cancer recurrence, treatment-related health risks, and mortality. Lack of information regarding long-term health outcomes can perpetuate these concerns. Therefore, we assessed all-cause and cause-specific mortality in a large cohort of individuals diagnosed with low-risk DTC. Methods: From the U.S. Surveillance, Epidemiology, and End Results-12 cancer registry database (1992-2019), we identified 51,854 individuals (81.8% female) diagnosed with first primary DTC at low risk of recurrence (≤4 cm, localized). We estimated cause-specific cumulative mortality by time since diagnosis, accounting for competing risks. Standardized mortality ratios (SMRs) and CIs were used to compare observed mortality rates in DTC patients with expected rates in the matched U.S. general population, overall and by time since DTC diagnosis. We used Cox proportional hazards models to examine associations between radioactive iodine (RAI) treatment and cause-specific mortality. Results: During follow-up (median = 8.8, range 0-28 years), 3467 (6.7%) deaths were recorded. Thyroid cancer accounted for only 4.3% of deaths (n = 148). The most common causes of death were malignancies (other than thyroid cancer) (n = 1031, 29.7%) and cardiovascular disease (CVD; n = 912, 26.3%). The 20-year cumulative mortality rate from thyroid cancer, malignancies (other than thyroid or nonmelanoma skin cancer), and CVD was 0.6%, 4.6%, and 3.9%, respectively. Lower than expected mortality was observed for all causes excluding thyroid cancer (SMR = 0.69 [CI 0.67-0.71]) and most specific causes, including all malignancies combined (other than thyroid cancer; SMR = 0.80 [CI 0.75-0.85]) and CVD (SMR = 0.64 [CI 0.60-0.69]). However, mortality rates were elevated for specific cancers, including pancreas (SMR = 1.58 [CI 1.18-2.06]), kidney and renal pelvis (SMR = 1.85 [CI 1.10-2.93]), and brain and other nervous system (SMR = 1.62 [CI 0.99-2.51]), and myeloma (SMR = 2.35 [CI 1.46-3.60]) and leukemia (SMR = 1.62 [CI 1.07-2.36]); these associations were stronger ≥10 years after diagnosis. RAI was not associated with risk of cause-specific death, but numbers of events were small and the range of administered activities was likely narrow. Conclusions: Overall, our findings provide reassurance regarding low overall and cause-specific mortality rates in individuals with low-risk DTC. Additional research is necessary to confirm and understand the increased mortality from certain subsequent cancers.

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.

Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project.

Background & Aims: Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. Methods: Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography-mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. Results: Higher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38-2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21-2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22-20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27-2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33-0.68). Conclusions: Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implications: This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.

Obesity, obesity-related metabolic conditions, and risk of thyroid cancer in women: results from a prospective cohort study (Sister Study).

Background: Thyroid cancer incidence has increased worldwide. Obesity trends may play a role, but the underlying biological pathways are not well-characterized. Therefore, we examined associations of excess adiposity and obesity-related metabolic conditions with thyroid cancer incidence. Methods: From the Sister Study, a cohort of sisters of women with breast cancer, we included 47,739 women who were cancer-free at baseline (2003-2009). Height, weight, waist and hip circumference, and blood pressure were measured at baseline and medical history was self-reported. Cox proportional hazards regression models were adjusted for age (time scale), race/ethnicity, smoking, baseline history of benign thyroid disease, and frequency of routine healthcare visits. Findings: During follow-up (median = 12.5; max = 15.9 years), 259 women reported incident thyroid cancer. Body mass index (BMI) (hazard ratio [HR]per-5 kg/m2 = 1.25, 95% CI = 1.14-1.37), waist circumference (HRper-5 cm increase = 1.11, 95% CI = 1.06-1.15), and waist-to-hip ratio (HR ≥0.85-versus-<0.85 = 1.49, 95% CI = 1.14-1.94) were positively associated with thyroid cancer incidence, as were metabolic syndrome (HR = 1.67, 95% CI = 1.24-2.25), dyslipidemia (HR = 1.46, 95% CI = 1.13-1.90), borderline diabetes (HR = 2.06, 95% CI = 1.15-3.69), hypertension (HR = 1.49, 95% CI = 1.12-1.96), and polycystic ovary syndrome (PCOS, HR = 2.10, 95% CI = 1.20-3.67). These associations were attenuated with additional BMI adjustment, although dyslipidemia (HR = 1.35, 95% CI = 1.04-1.75) and PCOS (HR = 1.86, 95% CI = 1.06-3.28) remained associated with thyroid cancer incidence. Hypothyroidism was not associated with thyroid cancer. Interpretation: In this cohort of sisters of women diagnosed with breast cancer, excess adiposity and several obesity-related metabolic conditions were associated with thyroid cancer incidence. These findings provide insights into potential biological mechanisms linking obesity and thyroid cancer. Funding: This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and National Institute of Environmental Health Sciences (Z01-ES044005).

NCIRF: an organ dose calculator for patients undergoing radiography and fluoroscopy.

Background. It is critical to monitor the radiation dose delivered to patients undergoing radiography and fluoroscopy to prevent both acute and potential long-term adverse health effects. Accurate estimation of organ doses is essential to ensuring that radiation dose is maintained As Low As Reasonably Achievable. We developed a graphical user interface-based organ dose calculation tool for pediatric and adult patients undergoing radiography and fluoroscopy examinations.Methods. Our dose calculator follows the four sequential steps. First, the calculator obtains input parameters related to patient age and gender, and x-ray source data. Second, the program creates an input file describing the anatomy and material composition of a phantom, x-ray source, and organ dose scorers for Monte Carlo radiation transport using the user input parameters. Third, a built-in Geant4 module was developed to import the input file and to calculate organ absorbed doses and skeletal fluences through Monte Carlo radiation transport. Lastly, active marrow and endosteum doses are derived from the skeletal fluences and effective dose is calculated from the organ and tissue doses. Following benchmarking with MCNP6, we conducted some benchmarking calculations calculated organ doses for an illustrative cardeiac interventional fluoroscopy and compared the results with those from an existing dose calculator, PCXMC.Results. The graphical user interface-based program was entitled National Cancer Institute dosimetry system for Radiography and Fluoroscopy (NCIRF). Organ doses calculated from NCIRF showed an excellent agreement with those from MCNP6 in the simulation of an illustrative fluoroscopy exam. In the cardiac interventional fluoroscopy exam of the adult male and female phantoms, the lungs received relatively greater doses than any other organs. PCXMC based on stylistic phantoms overall overestimated major organ doses calculated from NCIRF by up to 3.7-fold (active bone marrow).Conclusion. We developed an organ dose calculation tool for pediatric and adult patients undergoing radiography and fluoroscopy examinations. NCIRF could substantially increase the accuracy and efficiency of organ dose estimation in radiography and fluoroscopy exams.

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.

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.

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.