Coffee drinking and hepatocellular carcinoma: An update
Authors: Francesca Bravi, Cristina Bosetti, Alessandra Tavani, Carlo La Vecchia
Journal: Hepatology (2009)

We reviewed in a meta-analysis data from six case-control and four cohort studies on coffee and hepatocellular carcinoma (HCC) published between 1966 and February 2007.1 The summary relative risk (RR) estimate for coffee drinkers versus nondrinkers was 0.59 (0.54 from case-control and 0.64 from cohort studies). The RR was 0.42 (95% confidence interval [CI]: 0.32-0.55) for drinkers of three or more cups per day, but this estimate was based on limited data from case-control studies, mainly coming from Southern Europe. Since then, four prospective studies were published, including a total of 473 cases of HCC. A nested case-control study, conducted as part of the Japanese Collaborative Cohort Study for Evaluation of Cancer Risk, and reporting information on 106 HCC cases out of 110,792 subjects followed for 11 years, found a RR of 0.49 for daily coffee drinkers versus nondrinkers, 0.31 in hepatitis C virus (HCV)-positive subjects and 0.75 in HCV-negative subjects.2 A Finnish prospective study of 60,323 subjects followed for 19 years, and including 128 liver cancer cases, reported RRs around 0.5 for moderate coffee drinkers (two to five cups per day) and of 0.32 for drinkers of at least eight cups of coffee per day.3 A Japanese nested case-control study on 224 HCC cases, conducted within the longitudinal cohort of atomic bomb survivors, showed a RR of 0.40 for daily coffee drinkers as compared to nondrinkers.4 In the Japan Public Health Center-Based Prospective Study Cohort II, which included 18,815 subjects followed for 13 years and 110 incident cases of liver cancer affected by HCV or hepatitis B virus (HBV), the RRs were 0.67 for fewer than one cup per day, 0.49 for one to two cups, and 0.54 for three or more cups of coffee per day.5 We computed the summary RRs and the corresponding CIs for coffee drinkers, and for various levels of coffee consumption versus nondrinkers, applying the same methods of the previous meta-analysis.1 Briefly, we performed a Medline search of the literature from 1966 to June 2009, using the MeSH terms "coffee" and combinations of "hepatocellular" or "liver" and "carcinoma" or "neoplasm." We also cross-checked the reference list of the publications retrieved. To compute summary RRs, we used the fixed effect model,6 and random effect model when a significant heterogeneity was found.7 We calculated summary estimates for the two study types (case-control and cohort) separately, as well as in combination. Forest plots were given, in which a square was plotted for each study whose center projection on the underlying scale correspond to the study-specific RR. A diamond was used to plot the summary RRs, the center of which represents the RR, whereas the extremes show the 95% CI. Figure 1 shows the RR for coffee drinkers versus nondrinkers and low coffee drinkers and high coffee drinkers as compared to nondrinkers, in case-control studies, cohort studies, and overall. For coffee drinkers, the summary RR was 0.57 (95% CI: 0.49-0.67, Pheterogeneity < 0.01) from all studies, 0.54 (95% CI: 0.38-0.76, Pheterogeneity < 0.01) from case-control, and 0.60 (95% CI: 0.53-0.67) from cohort studies. For low or moderate coffee drinkers, the summary RR was 0.69 (95% CI: 0.59-0.81, Pheterogeneity = 0.04) from all studies, 0.68 (95% CI: 0.48-0.96, Pheterogeneity < 0.01) from case-control, and 0.68 (95% CI: 0.60-0.78) from cohort studies. For heavy coffee drinkers, the summary RR was 0.44 (95% CI: 0.38-0.50) from all studies, 0.42 (95% CI: 0.32-0.55) from case-control, and 0.46 (95% CI: 0.37-0.57) from cohort studies. Summary relative risks of hepatocellular carcinoma for drinkers, low or moderate drinkers, and high drinkers versus nondrinkers. (A) Low or moderate consumption defined as fewer than three cups per day for Kuper et al. (2000), Gallus et al. (2002), Gelatti et al. (2005), Inoue et al. (2005), Montella et al. (2007), Hu et al. (2008), and Inoue et al. (2009), and as fewer than one cup per day for Ohfuji et al. (2006), Tanaka et al. (2007), Kurozawa et al. (2005), Shimazu et al. (2005), and Wakai et al. (2007). (B) High consumption defined as three or more cups per day for Kuper et al. (2000), Gallus et al. (2002), Gelatti et al. (2005), Inoue et al. (2005), Montella et al. (2007), Hu et al. (2008), and Inoue et al. (2009), and as one or more cup per day for Ohfuji et al. (2006), Tanaka et al. (2007), Kurozawa et al. (2005), Shimazu et al. (2005), and Wakai et al. (2007). Thus, in the present updated meta-analysis, we found a 43% reduction in the risk of HCC among coffee drinkers compared to nondrinkers. The apparent beneficial role of coffee consumption was found both in studies from Europe, where coffee is more frequently consumed, and from Japan, where coffee consumption is less frequent. Moreover, the additional cohort results are now consistent with those of case-control studies. Liver cancer is the third most common cause of cancer death worldwide, with about 600,000 deaths per year.8 Liver cancer is, however, largely avoidable, through HBV vaccination, control of HCV transmission, and reduction of alcohol drinking. Whether coffee drinking has an additional relevant role on liver cancer prevention remains open to discussion.9 This work was conducted the contribution of the Italian Association for Cancer Research, the Italian League Against Cancer and the Italian Ministry of Research (PRIN 2005, PRIN 2007). Francesca Bravi* , Cristina Bosetti*, Alessandra Tavani*, Carlo La Vecchia* , * Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy, Università degli Studi di Milano, Istituto di Statistica Medica e Biometria "G.A. Maccacaro", Milan, Italy.