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Genetic variants at 5p15 have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants at 5p15 are important in the development of gastric cancer. To test this hypothesis, we evaluated the associations of genetic variants at 5p15 with gastric cancer based on our existing genome-wide association study (GWAS) data set of gastric cancer (1006 cases and 2273 controls), and replicated two promising loci in an independent case–control study with 1681 gastric cancer cases and 1705 controls in a Chinese population. We found that rs10052016 was consistently associated with gastric cancer risk in GWAS discovery stage (odds ratio [OR] = 0.69, 95% confidence interval [95% CI] = 0.55–0.87) and replication stage (OR = 0.80, 95% CI = 0.68–0.94). After combining these two studies, we found that the G allele of rs10052016 (at 132 kb upstream ofTERT) was significantly associated with a decreased risk of gastric cancer (OR = 0.76, 95% CI = 0.67–0.87,P= 5.35 × 10–5). Moreover, the protective allele of rs10052016-G was also significantly associated with late onset of gastric cancer (P= 0.013). In summary, these findings indicate that genetic variants at 5p15 may contribute to gastric cancer susceptibility and may further advance our understanding of 5p15 locus in cancer development.

Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations