Association of genetic variants in ATR-CHEK1 and ATM-CHEK2 pathway genes with risk of colorectal cancer in a Chinese population

Shijia Wang; Yue Zhang; Min Chen; Yong Wang; Yifei Feng; Ziwei Xu; Dongsheng Zhang; Yueming Sun; Zan Fu

doi:10.18632/oncotarget.24299

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Research Papers:

Association of genetic variants in ATR-CHEK1 and ATM-CHEK2 pathway genes with risk of colorectal cancer in a Chinese population

Shijia Wang, Yue Zhang, Min Chen, Yong Wang, Yifei Feng, Ziwei Xu, Dongsheng Zhang, Yueming Sun and Zan Fu _

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Oncotarget. 2018; 9:26616-26624. https://doi.org/10.18632/oncotarget.24299

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Abstract

Shijia Wang1,2, Yue Zhang1,2, Min Chen1,2, Yong Wang2, Yifei Feng2, Ziwei Xu2, Dongsheng Zhang2, Yueming Sun2 and Zan Fu2

1The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

2Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Correspondence to:

Zan Fu, email: [email protected]

Yueming Sun, email: [email protected]

Keywords: colorectal cancer; genetic variants; ATM; susceptibility

Received: July 20, 2017 Accepted: December 04, 2017 Epub: January 23, 2018 Published: June 01, 2018

ABSTRACT

Objective: The ATR-CHEK1 and ATM-CHEK2 pathway have been confirmed to be related with the DNA damage response (DDR). Many studies have reported that genetic variants in ATR/CHEK1 and ATM/CHEK2 are associated with cancer risk. However, the association between genetic variants in ATR-CHEK1, ATM-CHEK2 pathway genes and colorectal cancer susceptibility is still unknown. In this study, we aim to explore whether these variants are correlated with the risk of colorectal cancer in a Chinese population.

Methods: A hospital-based case-control study, including 1,121 cases and 1,056 controls was conducted to evaluate the association between eight selected single nucleotide polymorphisms (SNPs) (rs35514263 in ATR; rs492510, rs558351 in CHKE1; rs189037 in ATM; rs2236141, rs5762748, rs2236142 and rs9620817 in CHEK2) in ATR-CHEK1 and ATM-CHEK2 pathways and the risk of colorectal cancer in a Chinese population by using TaqMan method.

Results: Individuals with rs189037 A allele were found to have a significantly increased risk of colorectal cancer, compared to those carrying G allele [odds ratio(OR) = 1.23, 95% confidence interval (CI) = 1.02–1.47 in dominant model and OR= 1.14, 95%CI= 1.01–1.29 in additive model]. And this risk is more pronounced in elder people (>69), rectum, early stage and poorly grade. In addition, bioinformatic analysis showed that rs189037 may change the secondary structure.

Conclusions: Our results provide the evidence that rs189037 in ATM may increase the susceptibility of colorectal cancer in a Chinese population.

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Research Papers:

Association of genetic variants in ATR-CHEK1 and ATM-CHEK2 pathway genes with risk of colorectal cancer in a Chinese population

Abstract