Recent genome-wide association studies (GWASs) have identified several germline variations associated with gastric cancer. The aim of this study was to investigate the individual and combination effects of those single nucleotide polymorphisms (SNPs), which related to the risk of early-onset gastric cancer in a Chinese Han population.
Data of characteristics of study subjects, such as age, sex, family history, etc., were collected from the medical record in the Peking University Cancer Hospital. Genomic DNA was extracted from venous blood. Polymerase chain reaction (PCR) methods were used to perform the genotyping.
We conducted a case-control study of 116 gastric cancer cases and 102 sex- age-matched controls, and confirmed that the SNPs MUC1 rs9841504 and ZBTB20 rs4072037 were associated with increased risk for gastric cancer in Han Chinese. Among the cases of gastric cancer, 65 of them had at least one direct lineal relative with carcinomas of the digestive system or breast/ovarian cancer. These cases had another four SNPs associated with the gastric cancer susceptibility - PSCA rs2294008, PLCE1 rs2274223, PTGER4 and PRKAA1 rs13361707, and TYMS rs2790. However, each of those low-penetrance susceptibility polymorphisms alone was not convincing enough to predict the absolute risk of early-onset gastric cancer. Thus, study of different combinations for polygenes was applied for our population. Population with both the risk alleles of MUC1 rs9841504 and ZBTB20 rs4072037 were associated with increased risk for gastric cancer for over 3 folds. Also, population of hereditary background with the risk alleles of PLCE1 rs2274223 and PTGER4 and PRKAA1 rs13361707 were 3 times more susceptible to cardia cancer than those without.
These findings provide evidence that, instead of single low-penetrance susceptibility variations, combination study of polymorphisms may result a high-risk classification for specific population.
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All authors have declared no conflicts of interest.