Genetic and Non-Genetic Risk Factors for Gastric Cancer: A Field Synopsis and Evidence from 934 Chinese Population Studies

Abstract

Background: China is one of the regions with the highest incidence, prevalence and mortality of gastric cancer worldwide. Yet, only few field synopses about non-genetic factors and genetic susceptibility in gastric carcinogenesis. The aim of this study is to summarize and assess the credibility and strength of non-genetic factors and genetic variation on the risk of gastric cancer. Methods: We used Chinese and international public databases to identify published studies that assessed associations between non-genetic factors and variants on candidate genes and the risk of gastric cancer in Chinese population. Cumulative epidemiological evidence of statistical relation was evaluate combining Venice criteria, a false-positive report probability (FPRP) test, attributable risk percentage (ARP) and population attributable risk percentage (PARP). Findings: A total of 622 articles (n=394 articles, 399 studies for non-genetic factors; n=532 articles, 535 studies for genetic factors) eligible articles were included in qualitative synthesis. A total of 16 common potential risk factors were extracted for non-genetic factors, and data on 1121 single nucleotide polymorphism (SNP) involving 441 distinct genes were available. We identified 14 non-genetic factors were significantly associated with gastric cancer risk: H. pylori infection, smoking, drinking, family history, stomach disease, high salt diet, pickled food, fast eating, irregular meals, edible hot food, smoked & frying, spicy diet, mental depression and diabetes. Meanwhile 22 variants were identified significantly associated with gastric cancer: 3 (PLCE1 rs2274223, PSCA rs2976392, MUC1 rs4072037) was high and 19 (MTHFR rs1801133, COX-2 rs20417, XRCC1 rs1799782 and rs25487, XRCC3, rs861539, NAT2 rs1799930 and rs1799929, PLCE1 rs3765524, GSTM1, GSTT1, IL-17A rs2275913 and rs8193036, PSCA rs2294008, PRKAA1 rs13361707, ERCC5 rs751402, TGFBR2 rs3773651, IL-10 rs1800896 and VDR rs731236) was intermediate level of summary evidence, respectively. As we add more non-genetic factors or susceptible genes to the model, the risk distribution expands, and the population can better distinguish high-risk and low-risk categories. For non-genetic factors, the top three for ARP were 66.33% (stomach disease), 54.34% (pickled food), and 49.75% (Smoked & frying). For PARP were 33.85% (pickled food), 24.73% (edible hot food) and 23.30% (H. pylori infection). On the basis of ARP and PARP associated with SNPs of gastric cancer, the top three for ARP were 53.91% (NAT2, rs1799929),53.05% (NAT2 phenotype), and 42.85% (IL-10, rs1800896). For PARP (CHB) were. 36.96% (VDR, rs731236), 25.58% (TGFBR2, rs3773651) and 20.56% (MUC1, rs4072037). Interpretation: We conducted the first field synopsis in Chinese population linking common non-genetic risk factors and DNA variation to summarize potential non-genetic and genetic risk factors for gastric cancer, and evaluate epidemiological indicators to identified high-quality biomarkers of gastric cancer. Our study provides referenced information for the non-genetic and genetic predisposition to gastric cancer. Funding Statement: This work was funded by the National Natural Science Foundation of China (81373097), Health Science and Technology Innovative Talents Project of Henan Province 2017, and Henan Medical Science and Technique Foundation (Co-sponsored by Province and Ministry, 2019). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was conducted based on the Meta-analysis of Observational Studies in Epidemiology (MOOSE), Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the systematic review principles of molecular association studies proposed by the Human Genome Epidemiology Network (HuGENet).