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 Xiong; Carol Giffen; Margaret A. Tucker; Sanford M. Dawsey; Neal D. Freedman; Christian C. Abnet; Alisa M. Goldstein; Philip R. Taylor

doi:10.1093/carcin/bgt094

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 journal › Article › peer-review

57 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	1536-1542
Number of pages	7
Journal	Carcinogenesis
Volume	34
Issue number	7
DOIs	https://doi.org/10.1093/carcin/bgt094
State	Published - Jul 2013
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

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10.1093/carcin/bgt094

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Li, W. Q., Hu, N., Hyland, P. L., Gao, Y., Wang, Z. M., Yu, K., Su, H., Wang, C. Y., Wang, L. M., Chanock, S. J., Burdett, L., Ding, T., Qiao, Y. L., Fan, J. H., Wang, Y., Xu, Y., Shi, J. X., Gu, F., Wheeler, W., ... Taylor, P. R. (2013). Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population. Carcinogenesis, 34(7), 1536-1542. https://doi.org/10.1093/carcin/bgt094

Li, WQ, Hu, N, Hyland, PL, Gao, Y, Wang, ZM, Yu, K, Su, H, Wang, CY, Wang, LM, Chanock, SJ, Burdett, L, Ding, T, Qiao, YL, Fan, JH, Wang, Y, Xu, Y, Shi, JX, Gu, F, Wheeler, W, Xiong, XQ, Giffen, C, Tucker, MA, Dawsey, SM, Freedman, ND, Abnet, CC, Goldstein, AM & Taylor, PR 2013, 'Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population', Carcinogenesis, vol. 34, no. 7, pp. 1536-1542. https://doi.org/10.1093/carcin/bgt094

@article{1afa41e87f9c4d1b99ab760960867237,

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

abstract = "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.",

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

note = "Funding Information: The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by the National Cancer Institute contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials were supported by National Cancer Institute contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute of the Chinese Academy of Medical Sciences. The current analysis was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute and the Division of Cancer Epidemiology and Genetics.",

year = "2013",

month = jul,

doi = "10.1093/carcin/bgt094",

language = "English (US)",

volume = "34",

pages = "1536--1542",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "7",

}

TY - JOUR

T1 - Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population

AU - Li, Wen Qing

AU - Hu, Nan

AU - Hyland, Paula L.

AU - Gao, Ying

AU - Wang, Zhao Ming

AU - Yu, Kai

AU - Su, Hua

AU - Wang, Chao Yu

AU - Wang, Le Min

AU - Chanock, Stephen J.

AU - Burdett, Laurie

AU - Ding, Ti

AU - Qiao, You Lin

AU - Fan, Jin Hu

AU - Wang, Yuan

AU - Xu, Yi

AU - Shi, Jian Xin

AU - Gu, Fangyi

AU - Wheeler, William

AU - Xiong, Xiao Qin

AU - Giffen, Carol

AU - Tucker, Margaret A.

AU - Dawsey, Sanford M.

AU - Freedman, Neal D.

AU - Abnet, Christian C.

AU - Goldstein, Alisa M.

AU - Taylor, Philip R.

N1 - Funding Information: The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by the National Cancer Institute contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials were supported by National Cancer Institute contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute of the Chinese Academy of Medical Sciences. The current analysis was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute and the Division of Cancer Epidemiology and Genetics.

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

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JO - Carcinogenesis

JF - Carcinogenesis

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ER -

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

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