Consumption of Coffee Associated With Reduced Risk of Liver Cancer

A Meta-Analysis

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


BMC Gastroenterol. 2013;13(34) 

In This Article


Search Strategy

We searched Medline (via PubMed; National Library of Medicine), EMBASE (Elsevier, Amsterdam, the Netherlands), ISI Web of Science (Institute for Scientific Information, Philadelphia, Pennsylvania), and the Cochrane library (Wiley, Chichester, United Kingdom) for studies published up to May 2012. Key words searched were as follows: (coffee OR caffeine OR beverages OR diet OR drinking OR lifestyle) AND (liver OR hepatocellular OR digestive) AND (cancer OR carcinoma OR tumor OR neoplasm) AND (risk). No language restrictions were applied.

Inclusion and Exclusion Criteria

The inclusion criteria were: case–control or cohort study; data on the frequency of coffee consumption; primary outcome defined as liver cancer or hepatocellular carcinoma; and relative risk (RR) estimates, odds ratios (ORs) or hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). Exclusion criteria included duplicate reports and insufficient data about coffee consumption.

Data Extraction

The following data were collected from each publication: the name of the first author, year of publication, the country where the study was conducted, sex, study design, study population demographics, study period, sample size, type of outcome, consumption of coffee, number of exposed cases, the RRs or ORs or HRs and their 95%CIs, and covariates adjusted in the analysis. All data were extracted independently by three reviewers, and any disagreement was resolved by discussion between them. If results were published more than once, the results from the most recent one were selected. Because liver cancer is rare, the OR was assumed to be the same as RR and HR, and all results are reported as OR for simplicity.[9]

Quality Assessment

The study quality was assessed by the 9-star Newcastle-Ottawa Scale.[10] A full score is 9 stars, and a score ≥ 6 stars is considered to be high quality. The quality of case–control studies was assessed as follows: adequate definition of cases, representativeness of cases, selection of controls, definition of controls, control for the most important factor or the second important factor, exposure assessment, same method of ascertainment for all subjects, and non-response rate (Table 1). The quality of cohort studies was assessed as follows: representativeness of the exposed cohort, selection of the unexposed cohort, ascertainment of exposure, outcome of interest not present at start of study, control for the most important factor or the second important factor, outcome assessment, follow-up long enough for outcomes to occur, adequacy of follow-up of cohorts (Table 2).

Statistical Analysis

For the included studies, we determined pooled ORs (or RRs or HRs) with 95% CI for the highest versus lowest category of coffee consumption from each study. Since various sources of heterogeneity may exist owing to a variety of factors, we carried out subgroup analysis to investigate the influence of study design, study region, sex and history of liver disease on the heterogeneity.

Statistical heterogeneity was evaluated through the Q test and I2 statistic;[26] P < 0.10 was considered statistically significant.[27] If the heterogeneity was acceptable (I2 < 50%), a fixed effects analysis was conducted to calculate the pooled OR. In addition, a random effects model was used. The causes of heterogeneity were investigated by subgroup analyses. To evaluate whether publication bias might affect the statistical results, we applied Egger's test and Begg's method to assess bias through visual inspection of funnel plots;[28,29] all statistical analyses were conducted using STATA (version 11.0; StataCorp, College Station, TX, USA). All statistical tests were 2-sided.