Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population

Wen Qing Li, Nan Hu, Paula L. Hyland, Ying Gao, Zhao Ming Wang, Kai Yu, Hua Su, Chao Yu Wang, Le Min Wang, Stephen J. Chanock, Laurie Burdett, Ti Ding, You Lin Qiao, Jin Hu Fan, Yuan Wang, Yi Xu, Jian Xin Shi, Fangyi Gu, William Wheeler, Xiao Qin XiongCarol Giffen, Margaret A. Tucker, Sanford M. Dawsey, Neal D. Freedman, Christian C. Abnet, Alisa M. Goldstein, Philip R. Taylor

Research output: Contribution to journalArticlepeer-review


The DNA repair pathways help to maintain genomic integrityand therefore genetic variation in the pathways could affect thepropensity to develop cancer. Selected germline single nucleotidepolymorphisms (SNPs) in the pathways have been associated withesophageal cancer and gastric cancer (GC) but few studies havecomprehensively examined the pathway genes. We aimed to investigateassociations between DNA repair pathway genes and riskof esophageal squamous cell carcinoma (ESCC) and GC, usingdata from a genome-wide association study in a Han Chinesepopulation where ESCC and GC are the predominant cancers. In sum, 1942 ESCC cases, 1758 GC cases and 2111 controls fromthe Shanxi Upper Gastrointestinal Cancer Genetics Project (discoveryset) and the Linxian Nutrition Intervention Trials (replicationset) were genotyped for 1675 SNPs in 170 DNA repair-relatedgenes. Logistic regression models were applied to evaluate SNPlevelassociations. Gene- and pathway-level associations weredetermined using the resampling-based adaptive rank-truncatedproduct approach. The DNA repair pathways overall were significantlyassociated with risk of ESCC (P = 6.37 × 10-4), but not withGC (P = 0.20). The most significant gene in ESCC was CHEK2(P = 2.00 × 10-6) and in GC was CLK2 (P = 3.02 × 10-4). Weobserved several other genes significantly associated with eitherESCC (SMUG1, TDG, TP53, GTF2H3, FEN1, POLQ, HEL308,RAD54B, MPG, FANCE and BRCA1) or GC risk (MRE11A, RAD54L and POLE) (P < 0.05). We provide evidence for an associationbetween specific genes in the DNA repair pathways andthe risk of ESCC and GC. Further studies are warranted to validatethese associations and to investigate underlying mechanisms.

Original languageEnglish (US)
Pages (from-to)1536-1542
Number of pages7
Issue number7
StatePublished - Jul 2013
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research


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