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July 1, 2008 — Higher coffee consumption was associated with lower liver cancer risk but higher levels of gamma-glutamyltransferase (GGT) may increase risk for this disease, according to the results of a study reported in the July issue of Hepatology. "Only three Japanese prospective studies have suggested an inverse association between coffee drinking and liver cancer risk," write Gang Hu, from the Department of Public Health, University of Helsinki in Finland, and colleagues. "No prospective studies on the association between ... GGT and liver cancer risk have been reported. We aimed to determine the single and joint associations of coffee consumption and serum GGT with the risk of primary liver cancer." The study cohort consisted of 60,323 Finns who were 25 to 74 years of age and free of any cancer at enrollment. Median follow-up was 19.3 years (interquartile range, 9.3 - 29.2 years). Incident liver cancer was diagnosed in 128 participants during follow-up. Hazard ratios for liver cancer risk as a function of coffee consumption were multivariable-adjusted for age, sex, alcohol consumption, education, smoking, diabetes and chronic liver disease at baseline and during follow-up, body mass index was assessed.
Adjusted hazard ratios of liver cancer in participants who drank 0 to 1, 2 to 3, 4 to 5, 6 to 7, and more than 8 cups of coffee daily were 1.00, 0.66, 0.44, 0.38, and 0.32, respectively (P for trend = .003), and further adjustment for serum GGT in subgroup analysis affected the results only slightly. For the highest vs the lowest quartile of serum GGT, the multivariable-adjusted and coffee-adjusted hazard ratio of liver cancer was 3.13 (95% confidence interval, 1.22 - 8.07). Stratification by baseline factors did not abolish the multivariable-adjusted inverse association between coffee consumption and liver cancer risk; these factors included age younger than 50 years and 50 years and older, current smoker/never smoked/ever smoked, alcohol drinker/never drinker, obese/nonobese, and the highest/lowest 3 quartiles of serum GGT. Risk was increased nearly 9-fold for the combination of very low coffee consumption and high level of serum GGT. "Coffee drinking has an inverse and graded association with the risk of liver cancer," the study authors write. "High serum GGT is associated with an increased risk of liver cancer." Limitations of this study include use of self-reported data on coffee intake only at baseline; lack of data about other main sources of caffeine; no data on history of either hepatitis B virus or hepatitis C virus infections at baseline; use of only a dichotomized measure of alcohol consumption in the whole sample; and inability to completely exclude the effects of residual confounding due to measurement error. "The biological mechanisms behind the association of coffee consumption with the risk of liver cancer are not understood at present," the study authors conclude. "It would be interesting to find out whether the modification of coffee drinking would modify the risk of liver cancer in people positive for either HBV [hepatitis B virus] or HCV [hepatitis C virus] infection." In an accompanying editorial, Carlo La Vecchia, from Universitá degli Studi di Milano in Milan, Italy, notes the difficulties in translating the inverse relation between coffee drinking and liver cancer risk into potential implications for preventing liver cancer by increasing coffee consumption. "Together with avoidance of lung cancer through tobacco control, primary liver cancer is the other common neoplasm which is most largely avoidable, through HBV vaccination, control of HCV transmission, and reduction of alcohol drinking," Dr. La Vecchia writes. "These three measures can, in principle, avoid more than 90% of primary liver cancers worldwide. Whether coffee drinking has an additional role in liver cancer prevention remains open to discussion, but in any case any such role would be limited — if not negligible — as compared to that achievable through control of HBV, HCV, and alcohol consumption, which are the major recognized risk factors for liver cancer." The Finnish Academy and Special Research Funds of the Social Welfare and Health Board, City of Oulu, supported this study. The authors have disclosed no relevant financial relationships. The Italian Association for Cancer Research and the Italian League Against Cancer supported this work. Hepatology. 2008;48:7-9, 129-136. http://www.medscape.com
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