Abstract 2275: Serum retinol and risk of overall and site-specific cancer in the Alpha Tocopherol, Beta-Carotene Cancer Prevention Study

Abstract

Abstract Retinol, one of the most biologically active forms of vitamin A, influences many biologic pathways potentially related to cancer. However, results of observational studies of serum retinol and cancer risk have been mixed. We prospectively examined serum retinol and risk of overall and site-specific cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized, double-blind, placebo controlled trial of α-tocopherol (AT) and β-carotene (BC) supplementation conducted in male smokers in southwestern Finland. At enrollment, overnight fasting blood samples were collected and stored at -70°C protected from light. Serum retinol concentration was measured for all 29,133 participants using reverse-phase high performance liquid chromatography. 10,798 cancer cases occurred through 12/31/2012. Cox proportional hazards models were used to estimate the prospective association between quintiles of baseline serum retinol and overall and site-specific cancer incidence. Known or hypothesized risk factors for cancer were included in the multivariable model (AT and BC supplementation group, cigarettes smoked/day, years smoked, age, BMI, alcohol intake, and serum AT, BC, and cholesterol). Stratified analyses for all subgroups of the covariates (by category or by medians for continuous variables) and follow-up time to diagnosis (<10 vs. ≥10 y) were also performed for overall cancer and for the cancers for which an association with serum retinol was observed. After adjustment for age, higher serum retinol was associated with a lower risk of overall cancer (Q5 vs. Q1: HR=0.93, 95%CI=0.88-0.99, p-trend = 0.04). This finding was attenuated and no longer statistically significant after multivariable adjustment (MV-adj) (Q5 vs. Q1: MV-adj HR= 0.97, 95% CI = 0.91-1.03, p-trend = 0.43). Higher retinol concentrations were associated with increased risk of prostate cancer (Q5 vs. Q1: MV-adj HR=1.28, 95%CI = 1.13-1.45, p-trend < 0.0001) and lower risk of both lung and liver cancers (Q5 vs. Q1: liver MV-adj HR = 0.70, 95%CI = 0.50-0.99,p-trend = 0.03; lung MV-adj HR = 0.80, 95%CI = 0.72-0.88, p-trend < 0.0001). No associations with other cancers were observed. The inverse association between retinol and lung cancer was significantly modified by serum BC with a stronger association among men with higher serum BC (p for interaction = 0.018). No other statistically significant interactions were observed. In this large prospective study, higher serum retinol was associated with increased risk of prostate cancer and lower risk of lung and liver cancers. Understanding the biological mechanisms that underlie these associations may provide insight into retinol’s role in cancer prevention. Citation Format: Manila Hada, Alison Mondul, Stephanie Weinstein, Demetrius Albanes. Serum retinol and risk of overall and site-specific cancer in the Alpha Tocopherol, Beta-Carotene Cancer Prevention Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2275. doi:10.1158/1538-7445.AM2017-2275