Blood Transfusion, Alcohol Consumption, and Cigarette Smoking in Causation of Hepatocellular Carcinoma: A Case‐Control Study in Fukuoka, Japan

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Abstract
In the present study, we investigated the association between hepatocellular carcinoma (HCC) and hepatitis B virus infection (HBV), blood transfusion and drinking and smoking habits by comparing 124 HCC cases and 250 controls. We confirmed a very high relative risk (RR), i.e. 31.0 (P<0.001), among persons who were positive for serum hepatitis B surface antigen (HBsAg). However, the prevalence of serum HBsAg positives among our cases was only 21%, about half of those reported earlier, indicating a role of other etiological factors. Those who have a history of blood transfusion showed a significantly elevated RR of 3.0 (P<0.001) or 4.9 (P<0.001), and most of them (85%) were non‐carriers of HBV. Thus, the past history of blood transfusion is an important risk factor among the Japanese. Unidentified non‐A, non‐B hepatitis viruses in transfused blood probably play a significant role in causing HCC. We estimated that 15% of male HCCs were attributable to blood transfusion. A positive relationship between alcohol consumption and HCC was detected, particularly among HBsAg‐negative subjects with no history of blood transfusion who had drunk heavily in their younger years. RR estimates were not great (e.g., heavy drinkers: 2.5), but a substantial proportion of HCC may be attributed to drinking because of common drinking habits among Japanese males. Smoking was also found to have a positive association, but the relationship at a young age was less clear, and further investigation is needed to clarify the etiological role of smoking.