Variation by age, smoking, and menopausal status in the impact of body mass index change on liver cancer risk

The influence of age, smoking, and menopausal status on the association between changes in body mass index (BMI) and liver cancer risk remains largely unexplored. We enrolled cancer-free individuals who underwent national health examinations in 2010 and 2014, following them until 2021. BMI was classified as underweight, normal, overweight, obesity I, and obesity II, with BMI changes categorized into 25 groups. Among 3.8 million, 26,188 developed liver cancers. Persistent high BMI was associated with increased liver cancer risk compared to persistent normal BMI. Among individuals with obesity, further BMI gain (adjusted hazard ratio [aHR] 1.17; 95% confidence interval [CI] 1.04-1.31) and excessive BMI loss (aHR 1.29; 95% CI 1.14-1.46) raised liver cancer risk. Among individuals experiencing overweight, excessive BMI gain raised liver cancer risk in men (aHR 2.34; 95% CI 1.06-5.19), never smokers (aHR 2.22; 95% CI 1.00-4.94), and age ≥ 60 years (aHR 2.45; 95% CI 1.17-5.10). Among underweight and normal-weight women, excessive BMI gain increased cancer risk in premenopausal women (aHR 7.54; 95% CI 1.05-54.36). Excessive BMI loss increased liver cancer risk in most subgroups except premenopausal women. Our findings emphasize maintaining a normal BMI and reveal that excessive BMI changes are hazardous, with impacts varying across cofactors.