Abstract

Obesity relatively late in adulthood has been consistently associated with increased risk of primary liver cancer. However, little is known about the role of early adult adiposity and evolution of adiposity across adulthood in hepatocarcinogenesis. We examined adult body mass index (BMI; kg/m2 ) in relation to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a large prospective cohort. Weight at ages 18, 35, 50 and at study baseline was retrospectively reported by 303,620 participants. BMI trajectories were identified using latent class trajectory modeling. Incidence of HCC and ICC was determined through 2011. Cox proportional hazards modeling was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 372 HCC cases and 104 ICC cases occurred during follow-up. Being obese (BMI ≥ 30) at ages 18, 35, 50 and at baseline (mean age 62.3 years, range 50.3-71.5 years) was associated with an 86-119% elevated risk of HCC. BMI trajectories that resulted in obesity were associated with ∼80% higher HCC incidence. BMI at age 18, per 5 kg/m2 , was associated with a 34% higher risk of ICC, but the association attenuated for BMI at older ages. In conclusion, our findings suggest that maintaining a healthy BMI throughout the lifetime may reduce liver cancer risk. Future studies with longitudinally collected weight information are warranted to further elucidate the role of life-course adiposity in liver cancer development.

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