Consumption of Coffee Associated With Reduced Risk of Liver Cancer

A Meta-Analysis

Li-Xuan Sang; Bing Chang; Xiao-Hang Li; Min Jiang

Disclosures

BMC Gastroenterol. 2013;13(34) 

In This Article

Discussion

Coffee consumption has been suggested as a protective factor in the development of liver cancer, but evidence from observational studies is inconsistent.[11–25] The results of the current meta-analysis of seven prospective and nine case–control studies suggest that there is an inverse association between coffee consumption and liver cancer among different groups according to consumption level. There were significant reductions of 50% in the risk of liver cancer with the highest consumption of coffee compared with non/almost never consumption. The meta-analyses of Bravi et al.[30] found significant reductions of 55% in the risk of liver cancer with the high drinkers compared with non-drinkers, and Larsson & wolk[31] found a risk reduction of 43% per 2 cups of coffee per day increment. Our results are consistent with these two previous articles, partly because all of the studies in these two articles are included in the our meta-analysis.

Some results in this meta-analysis were heterogeneous, because the included studies had differences in study design, study region, study sex distribution, and control for confounding factors. In separate analyses by study design, we found an inverse association between coffee consumption and liver cancer among hospital- based case–control studies and among cohort studies.

There was also an inverse association between coffee consumption and liver cancer among European and Asian populations, and the significant risk reduction was stronger among Asian than European populations. The different results may be explained by racial differences. Differences in coffee drinking habits may be a partial explanation for the discrepancy.

We also found an inverse association between coffee consumption and liver cancer among male and female populations, but this result was derived from only four studies with a small number of cases, so we could not draw a firm conclusion. A history of liver disease may be a risk factor for liver cancer, and after adjustment for this, a significant inverse association remained between coffee consumption and liver cancer among two subgroups.

There are several potential mechanisms through which high consumption of coffee may reduce the risk of liver cancer. Coffee contains a variety of chemicals including caffeine, cafestol, kahweol, and chlorogenic acids. It remains uncertain which ingredient of coffee is protective against liver cancer. Some studies have indicated that caffeine can prevent oxidative DNA damage, modify the apoptotic response and reverse cell cycle checkpoint function.[32–34] Caffeine has strong antioxidant properties.[35] In an animal experiment, caffeine significantly reduced the incidence of chemically-induced hepatocellular carcinoma in rats.[36] Furthermore, cafestol and kahweol have been shown to be anti-carcinogenic.[37,38] Cafestol and kahweol have demonstrated a protective effect against aflatoxin B1-induced genotoxicity.[39] In addition, a study by Feng et al. showed that chlorogenic acids can scavenge reactive oxygen species and have an anti-tumor effect.[40] These studies suggest that ingredients in coffee may play an important role in protecting against the occurrence and development of liver cancer.

Our meta-analysis had some merits. First, the total number of cases included in this meta-analysis was substantial (n = 3622 liver cancer cases). The summary ORs of the highest compared with the lowest coffee consumption categories for risk of liver cancer were consistent with those in a previously published meta-analyses (n = 2260 liver cancer cases).[30,31] Second, we found little evidence of publication bias in our meta-analysis. Third, we performed a comprehensive search of the literature on the association between coffee consumption and liver cancer risk up to May 2012.

Our meta-analysis had several limitations. First, we used the highest and lowest coffee consumption levels as measures of exposure, but we were not able to determine whether different amounts of coffee consumption could decrease liver cancer risk. Second, misclassification bias should be considered. Each study presented coffee consumption in different units (cups/week, cups/day, days/week, drinks/day, times/week). Therefore, differential misclassification could bias the results. Third, because liver cancer is a multifactorial disease, it is uncertain whether other factors may have influenced the results. Fourth, the study areas covered in our meta-analysis only included Asia (Japan, China, Hong Kong) and Europe (Finland, Greece, Italy). Therefore, the value of our results is limited for other areas (Africa, America and Australia). Fifth, potential publication bias might have influenced the results, despite no bias indicated from either the funnel plot or Egger's test.

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