Coffee consumption, as a major and frequent dietary exposure in diverse cultures around the globe, has been shown to be associated with pancreatic cancer in epidemiological studies. However, there is no comprehensive, up-to-date overview of the entirety of the substantial body of epidemiologic evidence. To address this need, we quantitatively assessed the relationship between coffee intake and incidence of pancreatic cancer in a meta-analysis of cohort studies.
Coffee can potentially impact the etiology of cancer of various sites along multiple pathways, ranging from carcinogenesis to cellular apoptosis. A number of in vitro
studies suggest that caffeine can influence carcinogenesis through inhibition of DNA repair, and induction of mitotic events before DNA replication is completed[26-28
]. Porta et al[29
] argues that in exocrine pancreatic cancer, caffeine, other coffee compounds, or other correlates of coffee drinking could modulate Ki-ras activation by interfering with DNA repair, cell-cycle checkpoints, and apoptosis. However, for most cancer sites, there is a signiﬁcant amount of evidence to show that there is no detrimental effect following the consumption of up to 6 cups of coffee per day in relation to cancer occurrence. Through the meta-analysis of cohort studies, we found that compared with individuals who did not drink or seldom drank coffee per day, the pooled RR of pancreatic cancer was 0.82 (95% CI: 0.69-0.95) for regular coffee drinkers, 0.86 (0.76-0.96) for low to moderate coffee drinkers, and 0.68 (0.51-0.84) for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 4% reduced risk of pancreatic cancer (RR, 0.96; 95% CI: 0.90-1.02). Thus, the evidence presented above suggests that coffee intake might prevent pancreatic cancer occurrence in humans.
Over the past two decades, many studies have been carried out on coffee and pancreatic cancer following the early warning in the early 1980s that coffee consumption was related to pancreatic cancer risk. Some ecological[30
], and cohort[20,22
] studies carried out in the USA, Canada, Europe and Asia investigated the relationship between coffee consumption and the risk of pancreatic cancer. In general, these investigations yielded inconsistent results, with a meta-analysis on 25 case-control studies giving a summary effect estimate of 1.04 (95% CI: 1.00-1.07) and a summary RR of 1.00 (0.94-1.07) per 1 cup/d for 10 cohort studies[5
]. Since the WCRF report, Luo et al[25
] studied the association between drinking coffee and the risk of pancreatic cancer in a large population-based cohort study in Japan. Among 102 137 participants followed for an average of 11 years in which 233 incident cases of pancreatic cancer were identified, there was no increased risk of pancreatic cancer with coffee intake. A reduced risk was apparent among men who drank at least 3 cups of coffee per day compared with those who did not drink any or only rarely drank coffee. After a pooled analysis of 14 cohort studies, we found that there was a reverse association between coffee consumption and the risk of pancreatic cancer.
Some limitations of this meta-analysis should be acknowledged. First, as in all observational studies of diet and disease, the possibility of bias and confounding can not be excluded. However, cohort studies, which are less susceptible to bias because of the prospective design, also showed an inverse association between coffee consumption and risk of pancreatic cancer, suggesting that the finding is not likely attributable to recall and selection bias. Individual studies may have failed to adjust for potential known or unknown confounders. Second, our results are likely to be affected by the misclassification of coffee consumption. Coffee exposure is mostly assessed in relation to the number of cups of coffee consumed daily, weekly or monthly. However, most of the studies included in our meta-analysis did not provide information on coffee type, serving size, or brewing method. Serving sizes and brewing methods for coffee can vary substantially within and between countries. Standard coffee cups are larger in the United States than in Europe or Japan, and the difference in the strength of the coffee brewed may compensate for the different serving size between countries[32
]. Third, we extracted the risk estimates that reflected the greatest degree of the control potential confounders, because it was hard to obtain raw data from each study to conduct standardized adjustments. Therefore, it is probable that the results based on the adjustment for different confounders were different from those based on standardized adjustments. Finally, only published studies were included in our meta-analysis. Therefore, publication bias may have occurred although no publication bias was indicated from both visualization of the funnel plot and Egger’s test.
In summary, there is substantial evidence from both laboratory and animal studies on the favorable influence of coffee on the risk of pancreatic cancer. Although well designed studies, in particular randomized clinical studies among high risk populations, are needed to provide valuable insights into coffee consumption and the risk of pancreatic cancer, our meta-analysis which included 14 prospective cohort studies confirmed that coffee consumption is inversely associated with the risk of pancreatic cancer.