Lack of Association between Risk of Biliary Tract Cancer and Circulating IGF (Insulin-like Growth Factor) -I, IGF-II or IGF-binding Protein-3: A Nested Case-control Study in a Large Scale Cohort Study in Japan (JACC Study)

Biliary tract cancer, encompassing gallbladder and bile duct cancers, has a poor prognosis, but little is knownof the etiology. A nested case-control study was here conducted to evaluate the association between serum levelsof IGF-I, IGF-II and IGFBP-3 and death from biliary tract cancer. In a large scale cohort study, 35 gallbladderand 42 bile duct cancers were observed during the follow-up. For each subject in the case group, 1-3 controlsubjects (228 in total) were selected randomly, matched for sex, age (as near as possible) and residential area.The subjects were divided into tertiles by circulating levels of IGF-I, IGF-II or IGFBP-3. Using conditionallogistic regression, risks among the tertiles were compared adjusted for defecation, smoking and drinking habits.No remarkable differences in risks of gallbladder or bile duct cancer were observed among tertiles of IGF-I orIGF-II, and no remarkable trend was observed. Circulating IGFBP-3 showed an inverse U-shape associationwith gallbladder cancer and a U-shaped one with bile duct cancer. Associations between IGF-I or IGF-II andgallbladder or bile duct cancer thus were lacking or very weak. The observed U- and inverse U-shaped associationof IGFBP-3 with the cancers is not suggestiveof any meaningful relationships.