Environmental Protective and Risk Factors for Gastric Cancer: An Umbrella Review and Reanalysis of Meta-Analyses

Abstract

Purpose: Despite extensive research on gastric cancer (GC), efforts to consolidate the numerous associations between possible factors and GC risk remain lacking. This systematic review aimed to provide an overview of potential GC-associated pairs.

Materials and methods: We systematically searched PubMed, Embase, and Cochrane databases, from their inception to April 23, 2022, for eligible systematic reviews and meta-analyses to investigate the association between any possible factors and GC risk. After the inclusion of 75 systematic reviews and meta-analyses, 117 association pairs were examined. We reanalyzed the included meta-analyses and produced effect estimates using uniform analytical models. The certainty of the evidence for each association pair was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria.

Results: Iatrogenic factors, including antibacterial drugs, were associated with an increased risk of GC. Epstein-Barr virus and Helicobacter pylori infections were also associated with an increased risk of GC, while human T-lymphotropic virus type 1 (HTLV-1) infections were associated with a reduced risk. Dietary habit was a major factor influencing moderate to high GRADE associations. Positive associations were observed for heavy alcohol consumption (relative risk [RR], 1.13; 95% confidence interval [CI], 1.06-1.12), refined grain consumption (RR, 1.36; 95% CI, 1.21-1.53), and habitual salt intake (RR, 1.41; 95% CI, 1.04-1.91).

Conclusions: The associations between GC risk and dietary and nutritional factors were considerably heterogeneous, whereas other factors, such as lifestyle and iatrogenic and environmental exposures, were consistent across regions. Therefore, dietary interventions for GC prevention should be tailored specific to regions.

Trial registration: PROSPERO Identifier: CRD42020209817.

Keywords: Gastric cancer; Meta-analysis; Risk factors; Stomach cancer; Umbrella review.

Fig. 1. Flow diagram of the search and selection processes.

Fig. 2. Environmental, genetic, drug, lifestyle, and social factors associated with the risk of gastric cancer in overall (A), Asian (B), and non-Asian (C) regions. The results are based on random-effects models. The certainty of evidence underlying each association between risk/protective factors and gastric cancer was evaluated using the GRADE framework. Subgroup analyses of geographical regions were conducted at the individual-study level. This approach was referred to as “reanalysis” as it generated separate results by region for factors not originally assessed by region in the meta-analyses.

GRADE = Grading of Recommendations Assessment, Development, and Evaluation; ES = effect size; RR = risk ratio or relative risk; OR = odds ratio; CI = confidence interval; PPI = proton pump inhibitor; NSAID = non-steroidal anti-inflammatory drugs; HTLV-1 = human T-lymphotropic virus. ^*Helicobacter pylori eradication for asymptomatic patient; ^†Total, occupational, or recreational physical activity.

Fig. 3. Nutritional and dietary factors associated with the risk of gastric cancer in overall (A), Asian (B), and non-Asian regions (C). The results are based on random-effect models. The certainty of evidence underlying each association between risk/protective factors and gastric cancer was evaluated following the GRADE framework. A subgroup analysis of geographical regions was conducted at the individual-study level. This approach was referred to as “reanalysis” as it generated separate results by region for factors not originally assessed by region in the meta-analyses.

GRADE = Grading of Recommendations Assessment, Development, and Evaluation; ES = effect size; RR = risk ratio or relative risk; OR = odds ratio; CI = confidence interval. ^*High intake of vegetables, fruits, fish, low-fat milk, and whole grains; ^†High intake of all types of red and/or processed meats, refined grains, sweets, high-fat dairy products, and high-fat gravy.