This meta-analysis investigated the potential association between coffee consumption and gastric cancer risk, which based on 20 independent reports from 13 prospective cohort studies, involving 1,372,811 participants and 3,368 cases of new-onset gastric cancer. The results showed no appreciable overall association between coffee consumption and gastric cancer. Similar results were obtained in most subgroup analyses. Evidence of a nonlinear association of gastric cancer risk with coffee consumption was not observed.
Comparison with previous studies
There were two meta-analyses published in 2014 [40] and in 2015 [41] to investigate the evidence about coffee consumption and gastric cancer. Results of this current meta-analysis generally concur and further complement the findings of previous review in several important aspects. In contrast to our results, Shen et al. found an overall positive association of 1.24 (95 % CI: 1.03–1.49) between the risk of gastric cancer and coffee consumption. One possible reason was that the review by Shen and colleagues only included eight studies involving 312,993 participants, and a few studies were missed, which may overestimate the effect size. Additionally, the review did not fully investigate other subgroups except for gender, follow-up time and ethnicity and conduct the dose–response analysis. Xie et al. indicated that no significant association was observed between coffee consumption and gastric cancer risk, which was consistent with our result. Compared with the review, our meta-analysis added one large scare cohort study with larger sample size and many more cases, which significantly enhanced statistical power to detect the potential associations of coffee consumption with gastric cancer. More importantly, the nonlinear association between coffee consumption and gastric cancer was investigated in present meta-analysis.
In the subgroup analysis, we obtained two valuable and important findings. A main finding was that the association between coffee consumption and the risk of gastric cancer was significant in the United States from three studies comprising 500,825 participants, but not in European and Japanese populations, which was a very interesting phenomenon. According to the international statistic of U.S Census Bureau [42], we could get the total populations of countries included. Combining coffee consumption data of them from International Coffee Organization in 2010 [43], we could calculate the coffee consumption per capita. We found that coffee consumption per capita (0.14 bags) among European countries included in our meta-analysis were twice greater than in the United States (0.07 bags), but did not observe an association between the consumption of coffee and risk of gastric cancer in European countries. In included original studies, we found that the average dose of coffee consumption of highest categories in those European populations is larger than in the United States. Conversely, it suggested that whether coffee consumption might have protective effect on the incidence of gastric cancer in some degree or not. The finding hints us that it is needed to further explore the dose–response association between coffee consumption and the risk of gastric cancer in future studies. In linear dose–response analysis, we found that the pooled RR of gastric cancer risk for an increase of coffee intake 2 cups per day was 0.98 (95 % CI, 0.85–1.13), which indicated that there were a null inverse association between coffee and gastric cancer. The null association might result from the limited included studies. We could preliminarily speculate that the larger difference between the groups of the highest and the lowest coffee consumption categories, the lower the risk estimates, if coffee had a protective effect on gastric cancer risk. Therefore, the lower risk estimates could be explained in a few categories of coffee consumption of our included studies. On the contrary, if coffee had some effect on the risk of gastric cancer we would expect the pooled RR to approach the null when the references group of coffee consumption includes coffee drinkers. According to available data, the pooled RR compared the highest with the lowest groups (including coffee drinkers) was 1.13 (95 % CI, 0.89–1.42), which was from 8 studies with 12 reports involving 1,205,876 participants and 2,418 patients with gastric cancer. Of course, this was likely to be an accidental finding. Additionally, we suspected that there is a U-shaped association between coffee consumption and gastric cancer risk in some extent. However, in nonlinear dose–response analysis, we did not observe any nonlinear association between coffee consumption and gastric cancer risk to date, which were likely limited by statistical power (nine studies comprising 803,500 participants). It is unclear whether the lack of a nonlinear dose–response association between coffee consumption and the risk of gastric cancer was due to potentially unfavorable effects of coffee at higher consumption levels or was because of residual confounding from other gastric cancer risk factors related to coffee consumption. More studies are warranted to investigate the potential difference between the different ethnic backgrounds.
Interestingly, another important finding was that coffee consumption increased the risk of gastric cancer in the group of equal to or less than 10 years follow-up, but did not have statistically significant association for more than 10 years follow-up. One possible explanation to this finding was that most studies have usually measured coffee consumption only once at the beginning of the study, and have assessed the outcomes at the end of the follow-up. Additionally, individuals frequently make changes to their diet, thus, observational studies investigating the association of baseline coffee consumption with gastric cancer risk cannot adequately account for mutative trends in intake. However, to our knowledge, no study has examined the association between changes in coffee and the risk of gastric cancer. We might preliminarily speculate that the longer the follow-up duration, the more people could change their coffee intake, which might weaken the association between coffee consumption and gastric cancer risk. The interesting finding deserves attention from related researchers. More studies investigating the association between changes in coffee consumption and gastric cancer over time are needed, which will help to explore the dose–response relationship with them.
Coffee is a complex mixture of over a thousand chemicals. Some constituents (such as very small amounts of aromatic hydrocarbons and heterocyclic amines) have been described as having genotoxic and mutagenic properties [11, 44]. For example, coffee contains acrylamide and caffeine, which have potential carcinogenic effects [45, 46]. In contrast, coffee contains many bioactive compounds including phenolic acids with strong antioxidant properties and cafestol and kahweol with anticarcinogenic activity [47]. Our findings provided an importantly open research thought for whether coffee consumption indeed had some degree protective effect on the incidence of gastric cancer or not. However, it lacked comprehensively biological mechanism research at the moment. Thus, both population and animal studies are needed to strengthen the exploration of biological mechanisms that link the coffee consumption and gastric cancer.
It is well acknowledged that the coffee bean types [48, 49], and roasting procedure [50] might affect coffee chemical composition [51]. We could preliminarily speculate that the difference conducting among geographic region might be that the type of coffee beans (Robusta versus Arabica), brewing methods (Instant, soluble, roast and ground), and caffeine content vary among ethnic groups and cultures. However, most of our included studies did not provide above detail information about coffee consumption characteristics.
Our study was unable to estimate the association between decaffeinated coffee and gastric cancer risk, because only one study separately reported the risk estimates between them. However, the study analyzing decaffeinated coffee consumption [39] found no relation with gastric cancer risk. It is not possible to separate the drinkers of both caffeinated and decaffeinated coffee from drinkers of decaffeinated coffee only. In general, drinkers consumed low amount of decaffeinated coffee [51].
Strengths and limitations
Our review is very valuable and crucial though it is an updated meta-analysis. Firstly, we not only included the prospective cohort studies, also added 4 times as many participants as the previous review, which provided stronger and more reliable evidence. Secondly, on the basis of our subgroup analysis, a significantly positive association between coffee consumption and gastric cancer risk was observed in the United States populations, which provided a clue for future study of how the biological mechanisms of coffee consumption and gastric cancer are affected by ethnicity. Thirdly, we not only analyzed the association of higher coffee consumption with gastric cancer risk, but also conducted the dose–response analysis to evaluate the linear and non-linear relations by using all the categories of data, which could help to quantify the associations and examine the shape of these possible associations.
There are some limitations to this meta-analysis. Firstly, different methods of assessment were used in the included studies, and the units and cut-offs of coffee consumption were heterogeneous across different studies. Nevertheless, we used RRs for the highest versus the lowest category of coffee consumption, which could, to some extent, reduce the bias caused by different units. Secondly, the study relied on self-reported engagement in coffee consumption, which was likely to cause the misclassification of exposure, and may underestimate the reported associations. Thirdly, our meta-analysis did not take into consideration the differences of coffee bean types, brewing methods, and serving sizes for coffee among the included studies because of no sufficient information in the original studies.
Some suggestions should be considered in future research. Firstly, most of the studies included were conducted in the United States and Europe, while only two in Japan and one in Singapore. Given the underlying disease-effect discrepancy among different geographic locations and ethnicities, more studies should be conducted in other populations from Asian, African and South America. Secondly, in observational studies, investigators should pay attention to collect the information on the types of coffee bean, brewing methods, roasting procedure, preparation, cup size, and duration of use, which might allow more detailed analysis into the association between the characteristic of coffee consumption and gastric cancer risk. Thirdly, we should investigate the association of changes in coffee consumption with the occurrence of gastric cancer, and further accurately assess the association between coffee consumption and the risk of gastric cancer. Finally, coffee composition is very complex, thus, more population-based epidemiological investigations and animal experimental studies are needed to further explore the potential biological mechanisms link that the coffee intake and gastric cancer.