DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk

Abstract

Breast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes, i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair gene ERCC2 were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism) was carried out on the population with the MGB (Minor Groove Binder) probe technique which consists of the use of the allelic discrimination with the Taqman ® method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR) > 0.85 for Asn homozygous for ERCC2 312.

Xeroderma pigmentosum complementation group C single‐nucleotide polymorphisms in the nucleotide excision repair pathway correlate with prolonged progression‐free survival in advanced ovarian cancer

“…Only a few studies have examined the role of SNPs in the NER pathway in both ovarian cancer risk and response to chemotherapy. [9][10][11][12][13][14] Those studies demonstrated that variants in the xeroderma pigmentosum (XP) complementation family group of proteins can predict platinum sensitivity and survival outcomes. 9,10 Because of the potential importance of the NER pathway, we sought to determine whether single-nucleotide polymorphisms in this pathway could be a prognostic marker of response to platinum-based chemotherapy in ovarian cancer.…”

Genomic profiling of breast cancer

“…It has a BRCA1 C-terminal domain (BRCT) which is characteristic of proteins involved in cycle checkpoint functions and DNA damage. XRCC1 [75,76], XRCC3, and XPD (ERCC2) [76][77][78] are involved in DNA repair. Polymorphisms in these genes are associated with increased breast cancer risk.…”

Low-intensity red and infrared lasers affect mRNA expression of DNA nucleotide excision repair in skin and muscle tissue

“…NER operates in the presence of other enzymes, as the complex ERCC1 (excision repair cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) [24,25]. ERCC2 gene product is associated with DNA unwinding when its product (protein XPD) is expressed [26]. XPD proteins act in the process as temporary helicase rolling out double helix to find DNA lesions caused by free radicals [27] with subsequent lesion removal [28].…”