Coffee Drink may protect against Risk for Liver Cancer

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.

Clinical Context

According to the current authors, liver cancer is the third most common cause of death from cancer worldwide. The incidence rate is high in western and central Africa and southeastern and eastern Asia and low in most developed countries except Japan, and hepatitis B and C virus infections have been identified as causative factors in more than 75% of cases. However, according to the current authors, coffee consumption has been found to be inversely related to risk for primary liver cancer, whereas GGT levels has been linked to increased risk. Finns drink coffee daily and have a higher per capita consumption of coffee (11.4 kg/year) than others such as the Japanese (3.2 kg/year) and Americans (4.1 kg/year). The prevalence of primary liver cancer and of hepatitis B and C virus infection is low in the Finnish population, making it a good setting to test the hypothesis that coffee consumption protects against primary liver cancer.

This is a population-based prospective cohort study to examine the association between coffee consumption and GGT level and risk for primary liver cancer during 19 years of follow-up in the Finn population.

Study Highlights

• 7 independent surveys were conducted in 6 geographic areas of Finland between 1972 and 2002, and a randomly selected sample was drawn during 2 of the years, and stratified by area, sex, and age, according to the World Health Organization MONICA [MONItoring trends and determinants of CArdiovascular disease] protocol.
• Subjects included were those 25 to 64 years of age and 65 to 74 years with a total sample size of 62,015.
• After excluding those with any history of cancer and incomplete data, 29,286 men and 31,037 women were analyzed and observed.
• Participants completed a questionnaire at baseline for medical history, lifestyle, and demographics.
• Smoking was categorized as never, ex-smoker, and current smoker; diabetes was documented from disease registers, and participants were asked "How many cups of coffee do you drink daily?".
• 1 cup of coffee in Finland is 1 dL.
• Alcohol consumption was categorized as abstainers and users and also into 4 subgroups of consumption.
• Body mass index was calculated.
• GGT was determined from venous blood using a kinetic method.
• All cancers were identified using the Finnish Cancer Registry, and survey cohorts were followed with computer-based registry linkage to 2006.
• Primary liver cancer included all types of cancer, such as hepatocellular carcinoma, cholangiocarcinoma, and adenocarcinoma.
• Mean age was 45 years, mean body mass index was 26 kg/m², 60% to 72% were alcohol drinkers, 24% to 60% were current smokers, 7% had incident diabetes during follow-up, and less than 0.4% had chronic liver disease.
• Median coffee consumption was 5.0 cups, and only 6.9% reported no coffee consumption and 3.3% reported 1 cup a day.
• Coffee consumption was positively associated with body mass index and smoking and inversely related to education and serum GGT.
• After excluding those with chronic liver disease, the multivariate adjusted hazard ratios during the first 2 years of follow-up for liver cancer for those who drank 0 to 1, 2 to 3, 4 to 5, 6 to 7, and 8 or more cups daily were 1.00, 0.66, 0.43, 0.42, and 0.35, respectively (P for trend .013).
• For the entire cohort for a median follow-up of 19.3 years, the adjusted hazard ratios for 0 to 1, 2 to 3, 4 to 5, 5 to 6, 6 to 7 and 8 or more cups daily were 1.00, 0.66, 0.44, 0.38, and 0.32 (P for trend .003).
• When analysis was restricted to 1982 to 2002 (n = 37,842) for a median of 14.3 years of follow-up, the multivariate and GGT adjusted odds of liver cancer for 0 to 1, 2 to 3, 4 to 5, 6 to 7 and 8 or more cups daily were 1.00, 0.53, 0.41, 0.29, and 0.22 respectively (P for trend .018).
• A significant positive association was found for serum GGT and liver cancer risk, with a hazard ratio of 3.13 for the highest vs the lowest quartile of GGT, excluding those with chronic liver disease or those who died from any cause did not change this association.
• No interactions were found for age group, smoking, body mass index, and alcohol consumption.
• The association did not change for filtered vs pot-boiled coffee.
• Those who drank the least coffee (0-1 cups daily) and in the highest quartile of serum GGT level had a 9.2 times increased risk for liver cancer.
• There was no significant interaction between coffee intake and GGT level for the risk for liver cancer.
• The authors concluded that coffee consumption and serum GGT were independently associated with liver cancer risk.

Pearls for Practice

• Coffee consumption is associated with reduced risk for primary liver cancer in the Finnish population.
• Serum GGT level is associated with increased risk for primary liver cancer in the Finnish population.