Nucleotide Excision Repair Gene <i>ERCC2</i> and <i>ERCC5</i> Variants Increase Risk of Uterine Cervical Cancer

Abstract

PurposeDefects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer.Materials and MethodsTwenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed.ResultsThe most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type.ConclusionThe results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.

Association between ERCC5 gene polymorphisms and gastric cancer risk in a Chinese population

“…Previous studies have reported that the ERCC5 rs17655 polymorphism has important roles in the development of several kinds of cancer, such as colorectal cancer, uterine cervical cancer, lung cancer, laryngeal cancer, as well as breast cancer (Li et al, 2014;Liang et al, 2014;Joo et al, 2015;Na et al, 2015;Zeng et al, 2015). Li et al (2014) reported that the ERCC5 rs17655 polymorphism is correlated with susceptibility to laryngeal cancer, while Joo et al (2015) conducted a study in a Korean population, and found that it was associated with the development of cervical cancer.…”

“…Li et al (2014) reported that the ERCC5 rs17655 polymorphism is correlated with susceptibility to laryngeal cancer, while Joo et al (2015) conducted a study in a Korean population, and found that it was associated with the development of cervical cancer. Zeng et al (2015) conducted a meta-analysis of 9 studies, and found that this polymorphism might influence the development of colorectal cancer.…”

The association of integration patterns of human papilloma virus and single nucleotide polymorphisms on immune- or DNA repair-related genes in cervical cancer patients

“…In a previous study, we showed that genetic variants of excision base repair proficiency genes are strongly associated with cervical cancer compared with the healthy control population. This finding also suggests that an individual host’s base excision repair or nucleotide excision repair ability may facilitate HPV viral persistence and cervical carcinogenesis 9 . Based on these, we hypothesized that genomic susceptibility to DNA damage may explain the association between differential HPV integration and radiotherapy outcome in cervical cancer patients.…”

Somatic mutation load and spectra: A record of DNA damage and repair in healthy human cells

“…The mutator phenotype hypothesis postulates that increased mutation rates in cancer cells provides a fitness advantage by leading to tumor heterogeneity which may further contribute to the generation of resistant cell populations to chemotherapeutic agents (Loeb, 2001). Several examples can be found for factors leading to increased spontaneous or induced mutation rates in cells that are associated with heightened cancer risk and poor prognosis (Aaltonen et al, 1993; Cleaver and Crowley, 2002; Cunningham et al, 1998; Gansmo et al, 2017; Hart et al, 1977; Hecht, 2008; Joo et al, 2016; Loeb et al, 1974; Parsons et al, 1993). Over the last decade, several international consortia such as The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Pan Cancer Analysis of Whole Genomes (PCAWG) have undertaken efforts toward the sequencing and annotation of mutations in cancer exomes and genomes.…”