Sex and Ethnic Differences in the Association of Obesity With Risk of Hepatocellular Carcinoma

Background & Aims Obesity is associated with increased risk for hepatocellular carcinoma (HCC), but the risk associated with obesity may vary by sex or ethnicity. We examined whether the association of body mass index (BMI) with HCC incidence, as well as correlations of BMI with total, visceral, and hepatic adiposity, differs among ethnic groups. Methods We collected data from the Multiethnic Cohort Study, a population-based prospective cohort study of more than 215,000 men and women from Hawaii and California that was assembled from 1993 through 1996. After a median follow-up of 16.6 years, 482 incident HCC cases were identified among 168,476 participants. BMI and risk factor data were obtained from a baseline questionnaire. Cox regression analyses were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for HCC associated with BMI. The black subjects in the Southern Community Cohort Study were included as a replication cohort. Results BMI was associated with HCC in men (HR per 5 kg/m2 increase, 1.26; 95% CI, 1.12–1.42) but not in women (HR, 1.06; 95% CI, 0.90–1.25) ( Pinteraction = .009). Although BMI was strongly associated with HCC in Japanese, white, and Latino men, there was no association in black men ( Pinteraction = .002). Similarly, no association was found in the blacks who participated in the Southern Community Cohort Study. BMI correlated with total fat mass, measured by dual-energy x-ray absorptiometry, in men and women and in all ethnic groups ( R ≥ 0.9). However, there was a lower correlation value for BMI and visceral or liver fat measured by abdominal magnetic resonance imaging in black men ( R < 0.5) and in women ( R < 0.8). Conclusions On the basis of an analysis of data from the Multiethnic Cohort Study, the association between BMI and HCC differs between sexes and among ethnicities. The lack of association in black men warrants further investigation. Rather than studying markers of total adiposity, studies of obesity and HCC should move beyond BMI and use a better measure for fat-specific depots.