Published online Jan 21, 2020. doi: 10.3748/wjg.v26.i3.307
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
Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis.
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.
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.
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.
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.