title: Impact of radiation and hepatitis virus infection on risk of hepatocellular carcinoma.
abstract: In cohort studies of atomic bomb survivors and Mayak nuclear facility workers, radiation-associated increases in liver cancer risk were observed, but hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were not taken strictly into account. We identified 359 hepatocellular carcinoma (HCC) cases between 1970 and 2002 in the cohort of atomic bomb survivors and estimated cumulative incidence of HCC by radiation dose. To investigate contributions of radiation exposure and hepatitis virus infection to HCC risk, we conducted a nested case-control study using sera stored before HCC diagnosis in the longitudinal cohort of atomic bomb survivors. The study included 224 HCC cases and 644 controls that were matched to the cases on gender, age, city, and time and method of serum storage, and countermatched on radiation dose. The cumulative incidence of HCC by follow-up time and age increased significantly with radiation dose. The relative risk (RR) of HCC for radiation at 1 Gy was 1.67 (95% confidence interval: 1.22-2.35) with adjustment for alcohol consumption, body mass index (BMI), and smoking habit, whereas the RRs for HBV or HCV infection alone were 63 (20-241) and 83 (36-231) with such adjustment, respectively. Those estimates changed little when radiation and hepatitis virus infection were fit simultaneously. The RR of non-B, non-C HCC at 1 Gy was 1.90 (1.02-3.92) without adjustment for alcohol consumption, BMI, or smoking habit and 2.74 (1.26-7.04) with such adjustment.
  
  
  CONCLUSIONS
  These results indicate that radiation exposure and HBV and HCV infection are associated independently with increased HCC risk. In particular, radiation exposure was a significant risk factor for non-B, non-C HCC with no apparent confounding by alcohol consumption, BMI, or smoking habit.
authors.affiliation: Department of Clinical Studies, Hiroshima, Japan. nwaka@rerf.or.jp
authors.forename: Waka
authors.initials: W
authors.lastname: Ohishi
authors.forename: Saeko
authors.initials: S
authors.lastname: Fujiwara
authors.forename: John B
authors.initials: JB
authors.lastname: Cologne
authors.forename: Gen
authors.initials: G
authors.lastname: Suzuki
authors.forename: Masazumi
authors.initials: M
authors.lastname: Akahoshi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nishi
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006525:Hepatitis, Viral, Human / Q000150:complications*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D054043:Nuclear Weapons; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects