Adiposity, Adulthood Weight Change, and Risk of Incident Hepatocellular Carcinoma.

Prospective data are limited regarding dynamic adulthood weight changes and hepatocellular carcinoma (HCC) risk. We included 77,238 women (1980-2012) and 48,026 men (1986-2012), who recalled young-adult weight [age 18 years (women); 21 years (men)], and provided biennially updated information regarding weight, body mass index (BMI), and comorbidities. Overall adulthood weight change was defined as the difference in weight (kilograms) between young-adulthood and present. Using Cox proportional hazards models, we calculated multivariable adjusted HRs (aHR) and 95% confidence intervals (CI). Over 3,676,549 person-years, we documented 158 incident HCC cases. Elevated HCC risk was observed with higher BMI in both young-adulthood and later-adulthood [continuous aHRs per each 1 unit = 1.05; 95% CI = 1.02-1.09 (P trend = 0.019), and 1.08; 95% CI = 1.06-1.10 (P trend = 0.004), respectively]. Moreover, overall adulthood weight gain was also significantly associated with increased HCC risk (aHR per each 1-kg increase = 1.03; 95% CI = 1.01-1.08; P trend = 0.010), including after further adjusting for young-adult BMI (P trend = 0.010) and later-adult BMI (P trend = 0.008). Compared with adults with stable weight (±5 kg), the multivariable-aHRs with weight gain of 5-<10 kg, 10-<20 kg, and ≥20 kg were, 1.40 (95% CI = 0.67-2.16), 2.09 (95% CI = 1.11-3.95), and 2.61 (95% CI = 1.42-5.22), respectively. In two prospective, nationwide cohorts, adulthood weight gain was significantly associated with increased HCC risk. PREVENTION RELEVANCE: Our data suggest that maintaining a stable weight during adulthood, specifically by preventing weight gain, could represent an important public health strategy for the prevention of hepatocellular carcinoma. ©2021 American Association for Cancer Research.