Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population

Abstract

Two recent genome-wide association studies reported significant associations of genetic variants at 1q22, 10q23 and 20p13 with gastric cancer (GC) risk in Chinese populations. However, these findings have not been confirmed in other independent studies. Here, we performed an independent case-control study in a Chinese population by genotyping three loci (rs4072037A>G at 1q22, rs2274223A>G at 10q23 and rs13042395C>T at 20p13) in 1681 GC cases and 1858 controls. We found that rs4072037 at 1q22 and rs2274223 at 10q23 were significantly associated with risk of GC with per allele odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.63-0.81; P = 2.98 × 10(-7)] and 1.42 (95% CI: 1.27-1.58; P = 9.68 × 10(-10)), respectively. The association was more prominent for rs2274223 in female (OR = 1.86, 95% CI: 1.49-2.32) and gastric cardia adenocarcinoma (GCA) (OR = 1.71, 95% CI: 1.49-1.95). Furthermore, we combined the two single-nucleotide polymorphisms to evaluate the joint effect and found that the GC risk significantly increased with the number of risk allele increasing with a trend P value of 6.66 × 10(-16), and individuals with four risk alleles had a 3.28-fold (95% CI: 1.75-6.13) risk of GC compared with those having no risk alleles. However, no significant association was detected between rs13042395 at 20p13 and GC risk (OR = 1.04, 95% CI: 0.94-1.15; P = 0.452). In conclusion, our results indicate that genetic variants at 1q22 and 10q23 but not 20p13 may serve as candidate markers for GC susceptibility in the Chinese population.

Association of Genetic Polymorphisms at 1q22 but not 10q23 with Gastric Cancer in a Southern Chinese Population

“…SNPs rs4072037 and rs4460629 at locus 1q22 were significantly associated with an altered risk of GC, while no significant result for the SNPs at 10q23 was found, unlike previous reports (Abnet et al, 2010;Zhang et al, 2011).…”

“…Though the GC GWAS conducted by Abnet et al has been replicated in an eastern Chinese population (Zhang et al, 2011), and the significant associations with risk of GC were found for rs4072037 at 1q22 and rs2274223 at 10q23. As far as we know, these findings have not been confirmed in other independent studies.…”

Lack of Association of Common Polymorphisms in MUC1 Gene with H. pylori Infection and Non-cardia Gastric Cancer Risk in a Chinese Population

“…SNP rs4072037, located at the 5' end of exon 2 in MUC1 gene, controls the alternative splicing of MUC1 (Xu et al, 2009). In our study, the frequencies of AA, AG, and GG genotypes in controls were 62.7, 32.4, and 4.9%, respectively, which was similar to the data from other studies in Chinese population (Xu et al, 2009;Zhang et al, 2011) and those from HapMap Chinese data. And our results indicated that SNP rs4072037 was not significantly associated with non-cardia gastric cancer.…”

“…Furthermore, the same group failed to identify that rs4072037 was associated with the risk of gastric cancer in another study (He et al, 2013). Zhang et al found that SNP rs4072037 was significantly associated with both non-cardia gastric cancer and cardia gastric cancer in eastern Chinese population using a relatively larger sample size (Zhang et al, 2011). One possible explanation for the discrepancy between their study and ours is that the modulation of gastric cancer risk might depend not only on a single gene/single SNP, but also on a joint effect of multiple polymorphisms within different genes, or on close interaction between polymorphisms and environmental factors (Jiang et al, 2010).…”

“…Thus, MUC1 is often aberrantly expressed in stomach cancer, and it is a ligand for H. pylori (Ng et al, 2008). Susceptibility to H. pylori infection and gastric cancer appears to be associated with MUC1 allele length (Costa et al, 2008;Vinall et al, 2002 (Xu et al, 2009;Jia et al, 2010;Zhang et al, 2011) with controversial results (Abnet et al, 2010;He et al, 2013). Because gastric cancer has potential genetic heterogeneity among different populations, the current study was conducted to investigate whether common polymorphisms in MUC1 gene were associated with H. pylori infection, and with non-cardia gastric cancer risk in north-western Chinese Han population.…”