Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome

Abstract

Background DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1,APEX1,MUTYH,OGG1,NUDT1,XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome.MethodsFrom Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DNA repair SNPs and CRC were calculated using a weighted Cox proportional hazard regression model.ResultsHeterozygous variants of rs1799832 in NUDT1 (HR = 2.97, 95% CI = 1.51–5.83) and rs13181 in ERCC2 (HR = 2.69, 95% CI = 1.10–6.55) were significantly associated with an increased risk of CRC compared with wild‐type homozygous CC and TT genotypes, respectively. However, the variant CG+GG genotype of MUTYH rs3219489 was associated with a decreased risk of CRC (HR = 0.49, 95% CI = 0.26–0.91) compared with the homozygous CC wild‐type counterparts.ConclusionOur findings revealed that polymorphisms of DNA repair genes that include NUDT1,ERCC2, and MUTYH are associated with CRC in patients with Lynch syndrome in Chinese population. Further studies with large sample size are needed to confirm our findings.

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes

“…Therefore, considering the large spectre of action of the MMR pathway, an elevated number of interactions between MMR and other DNA repair SNPs is expected. Such hypothesis, in line with our findings, has been recently strengthened by a report [136] associating SNPs from different DNA repair pathways with CRC in Lynch syndrome patients, a cancer predisposition condition originated by germline MMR mutations. Finally, among SNP pairs presenting significant findings in this study, three are intra-pathway combinations involving either HR or MMR pathway SNPs.…”

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“…It is a mismatch repair gene and coordinates the activities of genes in the repair of mismatch mutations. This gene helps in the prevention of cancer development (Kamiza et al, 2018). An earlier investigation into the molecular basis of anilineinduced spleen toxicity found that tumor growth may be induced by an increase in the phosphorylation of the pRB protein and expression of cyclin-dependent kinases and cyclins which is followed by an increase in the cell cycle regulatory protein cyclins and a decrease in CDK inhibitors.…”