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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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC3314279 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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

Zhang Hanze H Jin Guangfu G Li Huizhang H Ren Chuanli C Ding Yanbing Y Zhang Qin Q Deng Bin B Wang Jianming J Hu Zhibin Z Xu Yaochu Y Shen Hongbing H

Carcinogenesis 20110322 6

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 ...[more]

PMID: 21427165

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Project description:PurposePrevious studies showed that peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPARγ, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC).Patients and methodsWe performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPARγ rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscantm Kit.ResultsThe PPARγ rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42-0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42-0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPARγ rs1801282 SNV was correlated with the risk of GC in subgroups of age ≥ 61, no smoking, and no alcohol consuming. We also confirmed that the PPARγ rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI ≥ 24 kg/m2. The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI ≥ 24 kg/m2.ConclusionThis study indicates that the PPARγ, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.

Dataset Information

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

Publications

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

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