The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility

Abstract

Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (XPA, XPC, XPG, ERCC1, ERCC2, and ERCC4) in 89 ovarian cancer cases and 356 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association. The result showed that both ERCC1 rs11615 and XPC rs2228000 were significantly associated with reduced risk of ovarian cancer under dominant genetic model (adjusted OR = 0.35, 95% CI = 0.20–0.61, P=0.0002 and adjusted OR = 0.49, 95% CI = 0.30–0.81, P=0.005 respectively). In addition, XPC rs2228001 and ERCC2 rs238406 had statistically significant association with the increased risk of ovarian cancer under dominant genetic model (adjusted OR = 1.72, 95% CI = 1.02–2.92, P=0.043 and adjusted OR = 2.07, 95% CI = 1.07–4.01, P=0.032 respectively). ERCC1 rs3212986 were related with the increased risk of ovarian cancer under recessive model (adjusted OR = 2.40, 95% CI = 1.30–4.44, P=0.005). In conclusion, our results indicated that ERCC1, XPC and ERCC2 might influence ovarian cancer susceptibility. Further research with large sample size is warranted to validate the reliability and accuracy of our results.

Overcoming Platinum and PARP-Inhibitor Resistance in Ovarian Cancer

“…This complex also plays a role in the HR pathway, repairing intra-strand crosslink. There is conflicting data regarding the validity of ERCC1 as a predictive biomarker of platinum resistance [47,[49][50][51][52][53][54][55][56][57]. Polymorphisms in other NER components (i.e., XPA, XPB, XPF, XPD) have shown no correlation with platinum resistance [58].…”

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

“…About half of the patients are photosensitive because they bear the mutation in XPB/ERCC3, XPD/ERCC2, or general transcription factor IIH subunit 5 (GTF2H5) [153]. Zhao et al analysed 17 SNPs in NER genes XPA, XPC, XPD/ERCC2, XPF/ERCC4, XPG, and ERCC1 in 89 OvC cases and 356 controls, and their results suggested that ERCC1, XPC, and XPD/ERCC2 may be linked to OvC susceptibility [154]. Although this study for the first time explored the association of core genes in NER pathway with OvC, it should be pointed out that the sample size was insufficient to link OvC susceptibility to particular genetic variations and further, authors were not able to measure the mRNA expression of ERCC1, XPC, and XPD/ERCC2 to validate their findings.…”

“…Ishibashi et al reported that in OvC cell lines, tyrosine kinase with immunoglobulin-like and EGF like domains 1 (TIE1) promotes XPC-dependent NER and this leads to decreased susceptibility to cisplatin-induced cell death [158]. Last but not least, a study in 559 EOC patients showed an association of ERCC1 polymorphisms rs11615 and rs3212986 with cisplatin resistance Zhao et al analysed 17 SNPs in NER genes XPA, XPC, XPD/ERCC2, XPF/ERCC4, XPG, and ERCC1 in 89 OvC cases and 356 controls, and their results suggested that ERCC1, XPC, and XPD/ERCC2 may be linked to OvC susceptibility [154]. Although this study for the first time explored the association of core genes in NER pathway with OvC, it should be pointed out that the sample size was insufficient to link OvC susceptibility to particular genetic variations and further, authors were not able to measure the mRNA expression of ERCC1, XPC, and XPD/ERCC2 to validate their findings.…”

The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma

“…Together with the Xeroderma pigmentosum F it forms an endonuclease, which also participates in homologous recombination and base excision repair (BER) 16. The ERCC1 protein plays crucial role in NER, so some studies suggested that ERCC1 polymorphisms could attribute to increased risk of several malignant diseases 17,18. The gene for the ERCC1 protein is located on the chromosome 19q13.32 and consists of 10 exons 19.…”