Modification by cofactors in the impacts of body mass index change on the risk of biliary tract cancers.

INTRODUCTION AND OBJECTIVES: The impact of body mass index (BMI) change on the risk of biliary tract cancer, considering effect modification by age, smoking, and menopausal status, remains unexplored. PATIENTS AND METHODS: Cancer-free individuals who underwent health examinations in 2010 and 2014 were followed until 2021. BMI categories included underweight, normal, overweight, obesity I, and obesity II, with BMI changes classified into 25 groups using baseline and follow-up BMI. We assessed cancer risk according to BMI change and modification by cofactors using Fine and Gray's sub-distribution hazard model. RESULTS: Among 3.8 million persons, 5,047 gallbladder and 8,339 bile duct cancers were detected. Persistent high BMI elevated the risk of BTC compared to persistent normal BMI. Among obese individuals, a modest BMI loss (from obesity I to overweight) decreased gallbladder cancer risk (aHR 0.87; 95% CI 0.77-0.99), wherein marked BMI loss (from obesity I to normal) increased bile duct cancer risk (aHR 1.30; 95% CI 1.07-1.58). Excessive BMI gain (from normal to obesity I) increased gallbladder cancer risk in smokers (aHR 1.71; 95% CI 1.01-2.92). The effect of BMI change on the risk of BTC was more pronounced in women, never smokers, and those under 60 years. Among overweight women, BMI loss and excessive BMI gain increased bile duct cancer risk in premenopausal women. The impact of persistent high BMI and BMI change on the risk of BTC was prominent in postmenopausal women. CONCLUSIONS: Maintaining a normal BMI is crucial for preventing BTCs. Excessive BMI changes confer varying risks by sex, age, smoking, and menopausal status.