Elizabeth K. Cahoon

Prospective study of ultraviolet radiation exposure and risk of cancer in the United States

Ecologic studies have reported that solar ultraviolet radiation (UVR) exposure is associated with cancer; however, little evidence is available from prospective studies. We aimed to assess the association between an objective measure of ambient UVR exposure and risk of total and site‐specific cancer in a large, regionally diverse cohort [450,934 white, non‐Hispanic subjects (50–71 years) in the prospective National Institutes of Health (NIH)‐AARP Diet and Health Study] after accounting for individual‐level confounding risk factors. Estimated erythemal UVR exposure from satellite Total Ozone Mapping Spectrometer (TOMS) data from NASA was linked to the US Census Bureau 2000 census tract (centroid) of baseline residence for each subject. We used Cox proportional hazards models adjusted for multiple potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of UVR exposure. Restricted cubic splines examined nonlinear relationships. Over 9 years of follow‐up, UVR exposure was inversely associated with total cancer risk (N = 75,917; highest versus lowest quartile; HR = 0.97, 95% CI = 0.95–0.99; p‐trend < 0.001). In site‐specific cancer analyses, UVR exposure was associated with increased melanoma risk (highest versus lowest quartile; HR = 1.22, 95% CI = 1.13–1.32; p‐trend < 0.001) and decreased risk of non‐Hodgkins lymphoma (HR = 0.82, 95% CI = 0.74–0.92) and colon (HR = 0.88, 95% CI = 0.82–0.96), squamous cell lung (HR = 0.86, 95% CI = 0.75–0.98), pleural (HR = 0.57, 95% CI = 0.38–0.84), prostate (HR = 0.91, 95% CI = 0.88–0.95), kidney (HR = 0.83, 95% CI = 0.73–0.94) and bladder (HR = 0.88, 95% CI = 0.81–0.96) cancers (all p‐trend < 0.05). We also found nonlinear associations for some cancer sites, including the thyroid and pancreas. Our results add to mounting evidence for the influential role of UVR exposure on cancer.

Sunlight and Other Determinants of Circulating 25-Hydroxyvitamin D Levels in Black and White Participants in a Nationwide US Study

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.

Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009

This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958–2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999–2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: −0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this decrease was more rapid in males compared to females. The lowest dose range that showed a statistically significant dose response using the sex-averaged, linear ERR model was 0–100 mGy (P = 0.038). In conclusion, this analysis demonstrates that solid cancer risks remain elevated more than 60 years after exposure. Sex-averaged upward curvature was observed in the dose response independent of adjustment for smoking. Findings from the current analysis regarding the dose-response shape were not fully consistent with those previously reported, raising unresolved questions. At this time, uncertainties in the shape of the dose response preclude definitive conclusions to confidently guide radiation protection policies. Upcoming results from a series of analyses focusing on the radiation risks for specific organs or organ families, as well as continued follow-up are needed to fully understand the nature of radiation-related cancer risk and its public health significance. Data and analysis scripts are available for download at: http://www.rerf.or.jp.

Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983–2008

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.

Immune-related conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans

Background:Case–control studies have reported an inverse association between self-reported history of allergy and risk of glioma, but cohort data are limited. Our objectives were to evaluate the associations of major groups of medically diagnosed immune-related conditions (allergy/atopy, autoimmune disease, diabetes, infectious/inflammatory disease) and to explore associations with specific conditions in relation to subsequent diagnosis of brain cancer in a large cohort study.Methods:We used hospital discharge records for a cohort of 4.5 million male US veterans, of whom 4383 developed primary brain cancer. Rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using time-dependent Poisson regression.Results:We found a significant trend of decreasing RRs for brain cancer with longer duration of allergy/atopy (P=0.02), but not for other conditions studied. Rate ratios of brain cancer for allergy/atopy and diabetes with duration of 10 or more years were 0.60 (95% CI: 0.43, 0.83) and 0.75 (95% CI: 0.62, 0.93), respectively. Several associations with specific conditions were found, but these did not withstand correction for multiple comparisons.Conclusions:This study lends some support to an inverse association between allergy/atopy and diabetes of long duration and brain cancer risk, but prospective studies with biological samples are needed to uncover the underlying biological mechanisms.

Use of nonsteroidal anti-inflammatory drugs and risk of basal cell carcinoma in the United States Radiologic Technologists study

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.

Prospective study of ultraviolet radiation exposure and risk of breast cancer in the United States.

Although there are few environmental risk factors for breast cancer, some epidemiologic studies found that exposure to solar UV radiation (UVR) may lower risk. Prior epidemiologic studies are limited by narrow ambient UVR ranges and lack lifetime exposure assessment. To address these issues, we studied a cohort with residences representing a wide range of ambient UVR. Using the nationwide U.S. Radiologic Technologists study (USRT), we examined the association between breast cancer risk and UVR based on ambient UVR, time outdoors, a combined variable of ambient UVR and time outdoors (combined UVR), and sun susceptibility factors. Participants reported location of residence and hours spent outdoors during five age periods. Ambient UVR was derived by linking satellite-based annual UVR estimates to self-reported residences. Lifetime values were calculated by averaging these measures accounting for years spent in that location. We examined the risk of breast cancer among 36,725 participants (n=716 cases) from baseline questionnaire completion (2003-2005) through 2012-2013 using Cox proportional hazards models. Breast cancer risk was unrelated to ambient UVR (HR for lifetime 5th vs 1st quintile=1.22, 95% CI: 0.95-1.56, p-trend=0.36), time outdoors (HR for lifetime 5th vs 1st quintile=0.87, 95% confidence interval (CI): 0.68-1.10, p-trend=0.46), or combined UVR (HR lifetime 5th vs 1st quintile =0.85, 95% CI: 0.67-1.08, p-trend=0.46). Breast cancer risk was not associated with skin complexion, eye or hair color, or sunburn history. This study does not support the hypothesis that UVR exposure lowers breast cancer risk.

Individual, environmental, and meteorological predictors of daily personal ultraviolet radiation exposure measurements in a United States cohort study.

Background Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements. Methods We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables. Results The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R2 = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R2 = 0.25). Conclusions In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.

Self-reported sunscreen use and urinary benzophenone-3 concentrations in the United States: NHANES 2003–2006 and 2009–2012

BACKGROUND Sunscreens protect against skin cancer and other harmful effects of solar ultraviolet radiation (UVR). Epidemiologic and public health surveys often rely on self-reported sunscreen use to estimate sun exposure and avoidance, but questions remain about the validity of self-reports. Benzophenone-3 (BP-3), a common sunscreen ingredient, can be detected in the urine. Prior studies suggest that BP-3 concentrations increase after application of sunscreen. OBJECTIVES The goal of this study was to assess the validity of self-reported frequency of sunscreen use in relation to urinary BP-3 concentrations in a representative sample of the general US population, including in sub-groups defined by age, sex and race/ethnicity. METHODS To assess the relationship between categorical self-reported sunscreen use and creatinine-corrected urinary BP-3 concentrations, we conducted a linear regression adjusted for age, sex, race/ethnicity, six-month time period, body mass index, education, and sun avoidance behaviors. We tested for effect modification by age, sex, ethnicity and time period of measurement using multiplicative interaction terms and a F test. RESULTS BP-3 was positively associated with self-reported frequency of sunscreen use across all ages, sexes, race/ethnicities, and time periods. Crude and multivariate adjusted models were all statistically significant. R-square was relatively low for all models, ranging from 0.15 to 0.43. CONCLUSIONS Urinary BP-3 is positively associated with self-reported frequency of sunscreen use in the general US population, even in groups with overall low sunscreen use. These results suggest that self-report is a valid, although weak, way of assessing relative frequencies of sunscreen usage in a population-based study.

Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident

Background The excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of 131I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error. Methods We examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996–2004, who had direct thyroid 131I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied. Results There was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy− (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy− (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy− (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy− (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053–0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2). Conclusions In summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.