Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: A prospective study in Japan

Background. An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. Methods: Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90 452 middle-aged and elderly Japanese subjects (43 109 men and 47 343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. Results: Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1-2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3-4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for greater than or equal to 5 cups per day = 0.24 [5% CI = 0.08 to 0.77], P-trend < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100 000 people over 10 years, but it was 214.6 cases per 100000 people with drinking coffee on a, daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR = 0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18])and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). Conclusions: In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC.