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
Processing time: 95 Days and 21.8 Hours
Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes. Previous studies have suggested that NER SNPs could make impacts on colorectal cancer (CRC) risk and prognosis.
Currently, most researches in this field are only focused on a few SNPs in partial NER genes. A comprehensive investigation based on a large-scale Chinese population remains lacking.
The study aimed to explore the association of all tagSNPs in NER pathway genes with 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.
We found that 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 in CRC patients.
Our findings suggested novel predictive SNPs in NER pathway genes for CRC risk and prognosis in a large-scale Chinese population.
The present study has referential values for the identification of NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC, and may also provide clues for the access to individualized early diagnosis and therapy of CRC patients.