Abstract A78: Body mass index and risk of incident gallbladder cancer: Results from two large U.S. prospective cohort studies

Abstract

Abstract Background and Aims: Gallbladder cancer, a relatively rare malignancy, is highly lethal with a 5-year relative survival rate of 15%. Men and women with cholesterol gallstones face higher risk of the disease, and little else is known of its etiology. Because obesity, usually defined by a high body mass index (BMI: weight in kg divided by height in meters squared), greatly increases risk for gallstones, excess body mass emerges as a candidate risk factor for gallbladder cancer. The lethality of gallbladder cancer makes prospective studies most useful. To date, prospective studies have been inconsistent, but limited data suggest higher risks among obese women, while results among men have been equivocal. The rarity of the cancer motivated us to combine cohorts to derive more stable risk estimates. We investigated the association between BMI and incident gallbladder cancer risk in two large U.S. cohort studies. Methods: The American Cancer Society's Cancer Prevention Study II Nutrition Cohort (CPS-II) is a prospective study of cancer incidence conducted among U.S. men and women who resided in 21 states with population-based state cancer registries. In 1992 or 1993, 184,194 adult participants, aged 40 to 93 years, completed a detailed, self-administered questionnaire that included body weight, physical activity and other lifestyle and medical factors. The NIH-AARP Diet and Health Study is a prospective study of men and women, aged 50 to 71 years, from six U.S. states and two metropolitan areas. In 1995 or 1996, 566,401 adult participants completed a self-administered questionnaire regarding demographic and lifestyle characteristics, including body weight and height. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI) for the association between BMI and incident gallbladder cancer risk, by study and sex, adjusting for covariates that included age at baseline, physical activity and cigarette smoking. Random-effects meta-analysis was used to combine results. Results: After exclusions, 154,493 (73,174 men and 81,319 women) CPS-II participants and 479,593 (192,095 men and 287,498 women) AARP participants remained in the final analytic cohorts; among analytic cohort participants. Twenty men and 50 women in CPS-II and 59 men and 53 women in AARP were diagnosed with an incident gallbladder cancer (ICD-O-3: 23.9) by the end of follow-up in June 2007 (CPS-II) and December 2006 (AARP). In the CPS-II study, there was a suggestive association between linear BMI, per 5 kg/m⁁2, and gallbladder cancer risk, although the risk estimates were not statistically significant in men (RR 1.31; 95%CI 0.75–2.28) or in women (RR 1.15; 95%CI 0.85–1.54). In the larger AARP cohort, BMI per 5 kg/m⁁2 was positively associated with risk of gallbladder cancer in men (RR 1.18; 95%CI 0.97–1.44) and in women (RR 1.14; 95%CI 1.03–1.25). Pooled estimates, from random-effects meta-analysis, found summary relative risks for a 5 kg/m⁁2 BMI increase of 1.19 for men (95%CI 0.99–1.44), 1.14 for women (95%CI 1.04–1.25), and 1.15 for men and women combined (95%CI 1.06–1.25). Conclusions: Results of this study suggest that BMI is positively associated with risk of incident gallbladder cancer among women and men. The lack of statistical precision in this study, and the lack of categorical comparisons for obese versus normal BMI due to small case numbers, highlights the necessity of pooling data from multiple prospective studies to assess the impact of energy balance indicators on risk of rarer cancers. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A78.