Open AccessPolymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome
Author(s) -
Kamiza Abram B.,
Hsieh LingLing,
Tang Reiping,
Chien HueiTzu,
Lai ChihHsiung,
Chiu LiLing,
Lo TsaiPing,
Hung KuanYi,
You JengFu,
Wang WenChang,
Hsiung Chao A.,
Yeh ChihChing
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.402
Subject(s) - mutyh , lynch syndrome , hazard ratio , colorectal cancer , medicine , single nucleotide polymorphism , oncology , proportional hazards model , population , genotype , dna mismatch repair , genetics , dna repair , gastroenterology , cancer , dna glycosylase , confidence interval , biology , gene , environmental health
Background DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH 1 , APEX 1 , MUTYH , OGG 1 , NUDT 1 , XRCC 5, XPA , and ERCC 2 single nucleotide polymorphisms ( SNP s) are associated with colorectal cancer ( CRC ) in Chinese population with Lynch syndrome. Methods From Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome. Hazard ratios ( HR s) and 95% confidence intervals ( CI s) for the association between DNA repair SNP s and CRC were calculated using a weighted Cox proportional hazard regression model. Results Heterozygous variants of rs1799832 in NUDT 1 ( HR = 2.97, 95% CI = 1.51–5.83) and rs13181 in ERCC 2 ( 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. Conclusion Our findings revealed that polymorphisms of DNA repair genes that include NUDT 1 , ERCC 2, 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.