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Background:To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Methods:Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. Results:In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = -15.8, P = .003) and nuclear ER-β (β = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = -42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions:Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.

BackgroundEpidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E.MethodsWe undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics.ResultsWe noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome.ConclusionVariants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks.ImpactThe effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR.

ImportanceObservational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium.ObjectiveTo test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men.Design, setting, and participantsThe Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35,533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11,267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study.InterventionsIndividual supplements of selenium (200 μg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate).Main outcomes and measuresIncident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract.ResultsDuring a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction.Conclusions and relevanceThese data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.Trial registrationClinicalTrials.gov Identifier: NCT00784225.

Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium.To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men.The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35,533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11,267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study.Individual supplements of selenium (200 μg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate).Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract.During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction.These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.ClinicalTrials.gov Identifier: NCT00784225.