Case–control study on cigarette smoking and the risk of hepatocellular carcinoma among Japanese

Emerging epidemiologic data suggest that cigarette smoking may increase the risk of hepatocellular carcinoma (HCC), yet considerable controversies (e.g. inconsistent dose–response relationships) still exist with this association. We examined whether smoking was associated with HCC risk in a case–control study including 209 incident HCC cases and two different control groups (256 hospital controls and 381 patients with chronic liver disease [CLD] without HCC). Comparison of HCC cases with CLD patients, but not with hospital controls, demonstrated a significantly increased risk of HCC for current smokers. After adjustment for sex, age, heavy drinking history and hepatitis virus markers, odds ratios (and 95% confidence intervals) for former and current smokers relative to never smokers were 1.0 (0.6–1.7) and 2.5 (1.4–4.6), respectively, against CLD patients, as compared with 0.8 (0.3–2.3) and 1.8 (0.6–5.1), respectively, against hospital controls. In terms of pack-years during lifetime, dose–response relationship was not evident against either control group (P trend = 0.43), but it became clearer for more recent cigarette use among CLD patients. For example, regarding cumulative cigarette consumption during the last 5 years, adjusted odds ratios (and 95% confidence intervals) for 1–4 and 5+ pack-years relative to no use were 1.9 (1.1–3.6) and 2.8 (1.5–5.2) (P trend = 0.003), respectively. These results suggest that cigarette smoking may play a crucial role in the late stage of HCC development and that CLD patients may benefit from their earliest smoking cessation. (Cancer Sci 2008; 99: 93–97)