title: Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study.
abstract: BACKGROUND
  Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).
  
  
  METHODS
  We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.
  
  
  RESULTS
  After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46-3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27-2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco-HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.
  
  
  CONCLUSIONS
  Our findings strongly implicate tobacco smoke as a causal factor of HCC development.
authors.affiliation: Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, MD3, Singapore 117597, Singapore. ephkwp@nus.edu.sg
authors.forename: W-P
authors.initials: WP
authors.lastname: Koh
authors.forename: K
authors.initials: K
authors.lastname: Robien
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Govindarajan
authors.forename: J-M
authors.initials: JM
authors.lastname: Yuan
authors.forename: M C
authors.initials: MC
authors.lastname: Yu
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006510:Hepatitis B Antibodies / Q000032:analysis; D018937:Hepatitis C Antibodies / Q000032:analysis*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D012907:Smoking / Q000009:adverse effects*
chemical_list: D006510:Hepatitis B Antibodies; D018937:Hepatitis C Antibodies