Hepatocellular carcinoma among atomic bomb survivors: Significant interaction of radiation with hepatitis C virus infections

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Abstract
We conducted a nested case-control study within the cohort of Japanese survivors of the 1945 atomic bombings to study the joint effects of HBV and HCV with radiation on the risk of HCC. Among subjects who received autopsies during 1954–1988, we analyzed archival tissue samples for 238 pathologically confirmed HCC cases and 894 controls who died from diseases other than liver cancer. Using logistic regression and adjusting for potential confounders and other factors, we found a statistically significant, supermultiplicative interaction between A bomb radiation and HCV in the etiology of HCC. Compared to subjects who were negative for HCV and radiation, ORs of HCC for HCV-positive subjects showed a statistically significant, greater than multiplicative increase for liver irradiation exposures in the second (>0.018–0.186 Sv, p = 0.04) and third (>0.186 Sv, p = 0.05) tertiles of non-zero radiation exposure but not for first tertile exposure (>0–0.018 Sv, p = 0.86). Limiting analysis to subjects without cirrhosis, HCV-infected subjects were at 58.0-fold (95% CI 1.99–∞) increased risk of HCC per Sv of radiation exposure (p = 0.017), a supermultiplicative interaction between radiation and HCV that was not found among subjects with cirrhosis (p = 0.67). We found no evidence of interaction between HBV infection and radiation exposure in the etiology of HCC, regardless of cirrhosis status (p = 0.58). We conclude that among survivors of the nuclear bombings of Hiroshima and Nagasaki, subjects who were both HCV-positive and radiation-exposed were at a significantly, supermultiplicatively increased risk of HCC without concurrent cirrhosis.