Synergism between obesity and alcohol in increasing the risk of hepatocellular carcinoma: a prospective cohort study.
Obesity and alcohol interact to increase the risk of death from liver failure in men. In the present study, we aimed to examine whether obesity and alcohol were multiplicative or additive in increasing the risk of hepatocellular carcinoma (HCC) in both men and women. We conducted a prospective, population-based study of 23,712 Taiwanese residents (50.3% men) from 7 townships who underwent an evaluation for liver disease and were followed for 11.6 years for incident HCC. The mean age was 47 (standard deviation, 10) years and the mean body mass index (weight (kg)/height (m)(2)) was 24 (standard deviation, 3). Overall, 305 cases of HCC were identified over 275,126 person-years of follow-up. Age, male sex, alcohol drinking, cigarette smoking, elevated alanine aminotransferase, serum hepatitis B surface antigen, anti-hepatitis C virus positivity, and diabetes mellitus were each statistically significant predictors of incident HCC in univariate analyses (P < 0.05). Alcohol use and obesity (body mass index ≥30) showed a synergistic association with the risk of incident HCC in both unadjusted analyses (hazard ratio = 7.19, 95% confidence interval: 3.69, 14.00; P < 0.01) and multivariable-adjusted analyses (age, sex, smoking, serum alanine aminotransferase, serum hepatitis B surface antigen, anti-hepatitis C virus antibody, and diabetes mellitus) (hazard ratio = 3.82, 95% confidence interval: 1.94, 7.52; P < 0.01). Relative excess risks due to interaction, attributable proportion, and synergy index were 4.83, 0.67, and 4.53, respectively, suggesting a multiplicative interaction between alcohol use and obesity. Obesity and alcohol synergistically increase the risk of incident HCC.
Division of Gastroenterology and Division of Epidemiology, University of California at San Diego, 9500 Gilman Drive, MC 0063, La Jolla, CA 92093, USA. roloomba@ucsd.edu
Rohit
R
Loomba
Hwai-I
HI
Yang
Jun
J
Su
David
D
Brenner
Elizabeth
E
Barrett-Connor
Uchenna
U
Iloeje
Chien-Jen
CJ
Chen
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects*; D000465:Algorithms; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D016001:Confidence Intervals; D048909:Diabetes Complications / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000150:complications; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013624:Taiwan / Q000453:epidemiology
D014408:Biomarkers, Tumor; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D000410:Alanine Transaminase