Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma

During a 4-year period from January 1995 to December 1998, blood samples an d questionnaire data were obtained from 333 incident cases of hepatocellula r carcinoma (HCC), as well as from 360 controls who were hospitalized for e ye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded ser a were tested for hepatitis B surface antigen (HBsAg) and antibodies to hep atitis C virus (anti-HCV) by third-generation enzyme immunoassays, and info rmation on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC ri sk [greater than or equal to 2 packs per day, odds ratio (OR) = 2.5]. This association was stronger in individuals without chronic infection with eith er HBV or HCV (greater than or equal to 2 packs per day, OR = 2.8). Consump tion of alcoholic beverages above a threshold of 40 glasses per week increa sed the risk of HCC (OR = 1.9). We also found evidence of a strong, statist ically significant and apparently super-multiplicative effect of heavy smok ing and heavy drinking in the development of HCC (OR for both exposures = 9 .6). This interaction was particularly evident: among individuals without e ither HBsAg or anti-HCV (OR for both exposures = 10.9). Coffee intake was n ot positively associated with HCC risk, but the reverse could not be exclud ed for the subgroup of chronically infected individuals. In conclusion, tob acco smoking and heavy alcohol consumption are associated with increased ri sk of HCC, especially when these 2 exposures occur together. Int. J. Cancer 85:498-502, 2000. (C) 2000 Wiley-Liss, Inc.