Li YK, Xu Q, Sun LP, Gong YH, Jing JJ, Xing CZ, Yuan Y. Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer. World J Gastroenterol 2020; 26(3): 307-323 [PMID: 31988591 DOI: 10.3748/wjg.v26.i3.307]
Corresponding Author of This Article
Yuan Yuan, MD, PhD, Professor, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, No. 155, Nanjingbei Street, Heping District, Shenyang 110001, Liaoning Province, China. yuanyuan@cmu.edu.cn
Research Domain of This Article
Genetics & Heredity
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Yan-Ke Li, Qian Xu, Li-Ping Sun, Yue-Hua Gong, Jing-Jing Jing, Cheng-Zhong Xing, Yuan Yuan, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Yan-Ke Li, Cheng-Zhong Xing, Department of Anorectal Surgery, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Yuan Y designed the study and revised the manuscript; Xing CZ recruited the patients; Sun LP collected the data; Xu Q, Gong YH, and Jing JJ performed the experiments; Li YK analyzed the data and drafted the manuscript.
Supported bythe National Key R&D Program of China, No. 2018YFC1311600.
Institutional review board statement: The study was approved by the Ethics Committee of the First Hospital of China Medical University.
Informed consent statement: All subjects provided written informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data is available.
STROBE statement: The guidelines of STROBE Statement have been adopted.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yuan Yuan, MD, PhD, Professor, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, No. 155, Nanjingbei Street, Heping District, Shenyang 110001, Liaoning Province, China. yuanyuan@cmu.edu.cn
Received: October 12, 2019 Peer-review started: October 12, 2019 First decision: November 27, 2019 Revised: December 26, 2019 Accepted: January 1, 2020 Article in press: January 1, 2020 Published online: January 21, 2020 Processing time: 95 Days and 21.8 Hours
Abstract
BACKGROUND
Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis.
AIM
To explore the association of all tagSNPs in NER pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage.
METHODS
Genotyping for NER SNPs was performed using kompetitive allele specific PCR. In the discovery stage, 39 tagSNPs in eight genes were genotyped in 368 subjects, including 184 CRC cases and 184 individual-matched controls. In the validation stage, 13 SNPs in six genes were analyzed in a total of 1712 subjects, including 854 CRC cases and 858 CRC-free controls.
RESULTS
Two SNPs (XPA rs10817938 and XPC rs2607775) were associated with an increased CRC risk in overall and stratification analyses. Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk. Another two SNPs (ERCC2 rs1052555 and ERCC5 rs2228959) were newly found to be associated with a poor overall survival of CRC patients.
CONCLUSION
Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population. The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.
Core tip: We conducted a two-stage case-control study to explore the association of all tag-single nucleotide polymorphisms (SNPs) in eight nucleotide excision repair pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population, including a discovery and validation stage. We newly found that two SNPs (XPA rs10817938 and XPC rs2607775) contributed to an increased CRC risk in overall and stratification analyses. Another two SNPs (ERCC2 rs1052555 and ERCC5 rs2228959) were also first reported to be associated with a poor CRC prognosis.
