Abstract A59: Serum 25-hydroxyvitamin D and risk of incident liver cancer and chronic liver disease mortality in Finnish men

Introduction: Vitamin D has generated great interest as a potential preventative agent of chronic disease. For example, laboratory studies suggest that vitamin D has anti-proliferative, anti-inflammation, pro-differentiation, and pro-apoptotic properties. Epidemiologic studies have linked high vitamin D levels with some cancers, yet few studies have examined possible associations with liver cancer or chronic liver disease. Therefore, we evaluated the association of serum 25-hydroxyvitamin D (25(OH)D) with incident liver cancer and chronic liver disease mortality in a case-control study nested within the prospective Alpha-Tocopherol and Beta-Carotene Cancer Prevention (ATBC) Study, a cohort of Finnish male smokers. Methods: The ATBC Study was a randomized primary prevention trial of α-tocopherol and β-carotene supplementation where 29,133 Finnish male smokers, aged 50-69, were recruited from 1985 to 1988 and randomized to daily supplementation of α-tocopherol (50 mg), β-carotene (20 mg), both, or placebo. Supplementation ended in April 1993 (median 6.1 years); however, participants have been followed since that time. At baseline, participants underwent a physical examination by registered nurses to measure height and weight, and to collect an overnight fasting blood sample. Participants also completed a baseline questionnaire concerning their tobacco smoking, general risk factors, diet and their medical history. Serum 25(OH)D levels was measured for 202 incident liver cancer cases (ICD-9=155 and ICD-10=C22), 225 chronic liver disease deaths (CD-9=571 and ICD-10=K70, K73, or K74) occurring between baseline and December 31, 2009, and 427 liver cancer-free controls matched with cases by age and date of blood draw. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, adjusting for age, date of blood draw, BMI, history of diabetes, number of cigarettes smoked per day, daily intakes of alcohol and coffee, serum α-tocopherol, β-carotene, and cholesterol. Results: High serum 25(OH)D levels were inversely associated with both incident liver cancer and chronic liver disease in models adjusted for age and date of blood draw. After multivariate adjustment, associations remained similar for incident liver cancer (season-specific quartile 4 (Q4) vs. quartile 1 (Q1) OR=0.53, 95% CI=0.31-0.89, P-trend=0.007) but were attenuated somewhat for chronic liver disease mortality (Q4 vs. Q1 OR=0.71, 95% CI=0.41-1.25, P-trend=0.23). Associations were similar in analyses using clinical vitamin D cutpoints and season-standardized quartiles, and in analyses stratified by season of blood collection and intervention group. Similar associations were also observed among cases occurring more than fifteen years after baseline and in analyses performed after excluding cases seropositive for hepatitis B and C viruses. Conclusions: Men with higher serum 25(OH)D levels had a lower risk of incident liver cancer. A similar pattern was observed for chronic liver disease mortality, although associations for this outcome were not statistically significant. Our observations suggest that high vitamin D status may protect against the development or progression of these diseases. Citation Format: Gabriel Y. Lai, Jian-Bing Wang, Stephanie J. Weinstein, Dominick Parisi, Ronald L. Horst, Philip R. Taylor, Katherine A. McGlynn, Satu Mannisto, Demetrius Albanes, Neal D. Freedman. Serum 25-hydroxyvitamin D and risk of incident liver cancer and chronic liver disease mortality in Finnish men. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A59.