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Single nucleotide polymorphisms (SNPs) of ERCC2, hOGG1, and XRCC1 DNA repair genes and the risk of triple-negative breast cancer in Polish women.

ABSTRACT: Triple-negative breast cancer (TNBC) refers to about 15-20% of all breast cancer cases. It is characterized by worse clinical outcome, poor prognosis, and absence of prognostic indicators. Several polymorphisms in the nucleotide excision repair (NER) and base excision repair (BER) gene have been extensively studied in association with various human cancers. The aim of this study was to evaluate the role of the hOGG1-Ser326Cys (rs13181), XRCC1-Arg194Trp (rs1799782), and ERCC2-Lys751Gln (rs13181) gene polymorphisms with clinical parameters and the risk for development of triple-negative breast cancer. Our research included 70 patients with TNBC and 70 healthy controls. Gene polymorphisms were genotyped by the PCR-RFLP (restriction fragment length polymorphism) method. The genotype distributions were contrasted by the chi-square test, and the significance of the polymorphism was assessed by multiple logistic regression producing odds ratios (ORs) and 95% confidence intervals (CIs). In the present work, a relationship was identified between ERCC2-Lys751Gln polymorphism and the incidence of triple-negative breast cancer. An association was observed between triple-negative breast carcinoma occurrence and the presence of Gln/Gln genotype (OR = 5.71 (2.12-5.43), p = 0.0007). A tendency for an increased risk of TNBC was detected with the occurrence of 751Gln allele of ERCC2 polymorphism. No significant associations between Ser326Cys and Arg194Trp genotype and TNBC were observed. We suggest that the Lys751Gln polymorphism of the ERCC2 gene may be risk factors for triple-negative breast cancer development in Polish women.

SUBMITTER: Smolarz B

PROVIDER: S-EPMC3980033 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Gly322Asp and Asn127Ser single nucleotide polymorphisms (SNPs) of hMSH2 mismatch repair gene and the risk of triple-negative breast cancer in Polish women.

Project description:Triple-negative breast cancer (TNBC) is characterised by worse clinical outcome and poor prognosis. The alterations in the oncogenes and tumor suppressor genes as well as microsatellite instability (MSI) have been associated with breast cancer development. It is knowledge that the most common mechanism inducing MSI in many cancer is genomic rearrangements found in the hMSH2 (human MutS homolog 2) gene. In this report we genotyped two polymorphisms of hMSH2 DNA repair gene in 70 TNBC patients and 70 age-matched cancer-free women using RFLP-PCR. The following polymorphisms were studied: an A/G transition at 127 positions producing an Asn/Ser substitution at codon 127 (the Asn127Ser polymorphism, rs17217772) and a G/A transition at 1032 position resulting in a Gly/Asp change at codon 322 (the Gly322Asp polymorphism, rs4987188). We found an association between the hMSH2 Asp/Asp and Gly/Asp genotypes and TNBC occurence. Variant Asp allele of hMSH2 decreased cancer risk [odds ratio (OR) 0.11; 95 % confidence interval (CI) 0.05-0.21]. The risk of TNBC in the carriers of the Gly322Gly-Asn127Ser combined genotype was increased (OR 3.71; 95 % CI 1.36-10.10). However the risk of TNBC was not alter by polymorphism Asn127Ser of the hMSH2 gene. The Gly322Asp polymorphism of the hMSH2 gene may be linked with TNBC occurrence in Polish women.

| S-EPMC4355438 | biostudies-literature

Single Nucleotide Polymorphisms (SNPs) of RAD51-G172T and XRCC2-41657C/T Homologous Recombination Repair Genes and the Risk of Triple- Negative Breast Cancer in Polish Women.

Project description:Double strand DNA breaks are the most dangerous DNA damage which, if non-repaired or misrepaired, may result in genomic instability, cancer transformation or cell death. RAD51 and XRCC2 encode proteins that are important for the repair of double-strand DNA breaks by homologous recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of triple-negative breast cancer. The polymorphisms of the XRCC2 gene -41657C/T (rs718282) and of the RAD51 gene, -172G/T (rs1801321), were investigated by PCR-RFLP in 70 patients with triple-negative breast cancer and 70 age- and sex matched non-cancer controls. The obtained results demonstrated a significant positive association between the RAD51 T/T genotype and TNBC, with an adjusted odds ratio (OR) of 4.94 (p = 0.001). The homozygous T/T genotype was found in 60 % of TNBC cases and in 14 % of the used controls. Variant 172 T allele of RAD51 increased cancer risk (OR = 2.81 (1.72-4.58), p < .0001). No significant associations were observed between -41657C/T genotype of XRCC2 and the incidence of TNBC. There were no significant differences between the distribution of XRCC2 -41657C/T genotypes in the subgroups assigned to histological grades. The obtained results indicate that the polymorphism of RAD51, but not of XRCC2 gene, may be positively associated with the incidence of triple-negative breast carcinoma in the population of Polish women.

| S-EPMC4550649 | biostudies-literature

An Association between Single Nucleotide Polymorphisms of Lys751Gln ERCC2 Gene and Ovarian Cancer in Polish Women.

Project description:Aim. The aim of this study was to evaluate the role of the Lys751Gln (rs13181) ERCC2 gene polymorphism in clinical parameters and the risk for development of ovarian cancer. Material and Methods. The study consisted of 430 patients with ovarian cancer (mean age: 53.2 ± 10.11) and 430 healthy subjects (mean age: 50.31 ± 18.21). Analysis of the gene polymorphisms was performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. Results. The results obtained indicate that the genotype Gln/Gln is associated with an increased risk of ovarian cancer (OR 5.01; 95% CI 3.37-7.43; p < 0.0001). Association of Lys751Gln polymorphism with histological grading showed increased ERCC2 Gln/Gln (OR = 6.96; 95% CI 3.41-14.21; p < 0.0001) genotype in grading 1 as well as Gln allele overrepresentation (OR = 4.98; 95% CI 3.37-7.40; p < 0.0001) in G1 ovarian patients. Finally, with clinical FIGO staging under evaluation, an increase in ERCC2 Gln/Gln homozygote frequencies in staging I and Gln allele frequencies in SI were observed. Conclusion. On the basis of these results, we conclude that ERCC2 gene polymorphism Lys751Gln may be associated with an increased risk of ovarian carcinoma.

| S-EPMC4615857 | biostudies-literature

XRCC1, but not APE1 and hOGG1 gene polymorphisms is a risk factor for pterygium.

Project description:PURPOSE: Epidemiological evidence suggests that UV irradiation plays an important role in pterygium pathogenesis. UV irradiation can produce a wide range of DNA damage. The base excision repair (BER) pathway is considered the most important pathway involved in the repair of radiation-induced DNA damage. Based on previous studies, single-nucleotide polymorphisms (SNPs) in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP-endonuclease-1 (APE1) genes in the BER pathway have been found to affect the individual sensitivity to radiation exposure and induction of DNA damage. Therefore, we hypothesize that the genetic polymorphisms of these repair genes increase the risk of pterygium. METHODS: XRCC1, APE1, and hOGG1 polymorphisms were studied using fluorescence-labeled Taq Man probes on 83 pterygial specimens and 206 normal controls. RESULTS: There was a significant difference between the case and control groups in the XRCC1 genotype (p=0.038) but not in hOGG1 (p=0.383) and APE1 (p=0.898). The odds ratio of the XRCC1 A/G polymorphism was 2.592 (95% CI=1.225-5.484, p=0.013) and the G/G polymorphism was 1.212 (95% CI=0.914-1.607), compared to the A/A wild-type genotype. Moreover, individuals who carried at least one C-allele (A/G and G/G) had a 1.710 fold increased risk of developing pterygium compared to those who carried the A/A wild type genotype (OR=1.710; 95% CI: 1.015-2.882, p=0.044). The hOGG1 and APE1 polymorphisms did not have an increased odds ratio compared with the wild type. CONCLUSIONS: XRCC1 (Arg399 Glu) is correlated with pterygium and might become a potential marker for the prediction of pterygium susceptibility.

| S-EPMC2890553 | biostudies-literature

Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants.

Project description:ObjectivesTo investigate whether polymorphisms in genes involved in the repair of oxidative DNA damage, modulate, and/or interact with antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas. Accumulating evidence indicates that oxidative stress plays a role in prostate carcinogenesis.MethodsCases (n = 193) included men aged 40-80 years, diagnosed with prostate cancer in 3 major hospitals in 1998-2003, and controls (n = 197) were matched to cases by age, race, and county of residence.ResultsAfter adjustment for confounders, subjects who were heterozygous or homozygous for the variant allele of the hOGG1 Ser326Cys polymorphism appeared to experience a lower risk of prostate cancer than those who were homozygous for the wild-type allele (odds ratio [OR] (95% confidence interval [CI]): 0.72 (0.46-1.10)]. Conversely, a significant increased risk was observed for individuals who carried 1 or 2 copies of the variant allele of the XRCC1 Arg399Gln polymorphism, compared with those who only harbored the wild-type allele (OR [95% CI]: 1.56 [1.01-2.45]). The above-mentioned associations were generally more pronounced among subjects with low plasma carotenoids or alpha-tocopherol (<median). Among subjects who had low plasma levels of beta-cryptoxanthin (<73 microg/L), possession of at least 1 copy of the XRCC1 399Gln allele conferred a greater than 2-fold elevated risk (OR [95% CI]: 2.64 [1.40-5.07]).ConclusionsOur study offers preliminary but intriguing data suggesting that variability in the capacity of repairing oxidative DNA damage influences susceptibility to prostate cancer and that these effects are modified by antioxidants.

| S-EPMC2850942 | biostudies-literature

Lack of association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and keratoconus in a Polish subpopulation.

Project description:IntroductionKeratoconus (KC) is a non-inflammatory thinning of the cornea and a leading indication for corneal transplantation. Oxidative stress plays a role in the pathogenesis of this disease. The products of the hOGG1 and MUTYH genes play an important role in the repair of oxidatively modified DNA in the base excision repair pathway. We hypothesized that variability in these genes may change susceptibility to oxidative stress and predispose individuals to the development of KC. We investigated the possible association between the c.977C>G polymorphism of the hOGG1 gene (rs1052133) and the c.972G>C polymorphism of the MUTYH gene (rs3219489) and KC occurrence as well as the modulation of this association by some KC risk factors.Material and methodsA total of 205 patients with KC and 220 controls were included in this study. The polymorphisms were genotyped with polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR-confronting two-pair primer techniques. Differences in genotype and allele frequency distributions were evaluated using the χ(2) test, and KC risk was estimated with an unconditional multiple logistic regression with and without adjustment for co-occurrence of visual impairment, allergies, sex and family history for KC.ResultsWe did not find any association between the genotypes and combined genotypes of the c.977C>G polymorphism of the hOGG1 gene and the c.972G>C polymorphism of the MUTYH gene and the occurrence of KC.ConclusionsOur findings suggest that the c.977C>G-hOGG1 polymorphism and the c.972G>C-MUTYH polymorphism may not be linked with KC occurrence in this Polish subpopulation.

| S-EPMC4624754 | biostudies-literature

Polymorphisms in nucleotide excision repair genes and susceptibility to colorectal cancer in the Polish population.

Project description:Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. Genetic polymorphisms in XP genes may be associated with a change in DNA repair capacity, which could be associated with colorectal cancer development. We assessed the association between 94 single nucleotide polymorphisms (SNPs) within seven XP genes (XPA-XPG) and the colorectal cancer risk in the Polish population. We genotyped 758 unselected patients with colorectal cancer and 1,841 healthy adults. We found that a significantly decreased risk of colorectal cancer was associated with XPC polymorphism rs2228000_CT genotype (OR 0.59; p < 0.0001) and the rs2228000_TT genotype (OR 0.29; p < 0.0001) compared to the reference genotype (CC). And an increased disease risk was associated with the XPD SNP, rs1799793_AG genotype (OR 1.44, p = 0.018) and rs1799793_AA genotype (OR 3.31, p < 0.0001) compared to the reference genotype. Haplotype analysis within XPC, XPD and XPG revealed haplotypes associated with an altered colorectal cancer risk. Stratified analysis by gender showed differences between the association of three SNPs: XPC rs2228000, XPD rs1799793 and XPD rs238406 in females and males. Association analysis between age of disease onset and polymorphisms in XPD (rs1799793) and XPC (rs2228000) revealed differences in the prevalence of these variants in patients under and over 50 years of age. Our results confirmed that polymorphisms in XPC and XPD may be associated with the risk of colorectal cancer.

| S-EPMC4330403 | biostudies-literature

DNA repair gene XRCC1 polymorphisms and bladder cancer risk.

Project description:BackgroundCigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects.ResultsWe found no evidence of an association between any of the 14 XRCC1 polymorphisms and bladder cancer risk. However, we found carriage of the variant Arg280His allele to be marginally associated with increased bladder cancer risk compared to the wild-type genotype (adjusted odds ratio [95% confidence interval], 1.50 [0.98-2.28], p = 0.06). The association was stronger for current smokers such that individuals carrying the variant 280His allele had a two to three-fold increased risk of bladder cancer compared to those carrying the wildtype genotype (p = 0.09). However, the evidence for gene-environment interaction was not statistically significant (p = 0.45).ConclusionWe provide no evidence of an association between polymorphisms in XRCC1 and bladder cancer risk, although our study had only limited power to detect the association for low frequency variants, such as Arg280His.

| S-EPMC1865553 | biostudies-literature

SNPs in ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway and risk of male infertility in the Asian populations: association study, meta-analysis, and trial sequential analysis.

Project description:PurposeWe investigated if substitutions in the ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway correlate with non-obstructive azoospermia and male infertility.MethodsA total of 548 azoospermic infertile males and 410 fertile controls were genotyped for XRCC1 399A > G, 280G > A, and ERCC1 C > A 3' UTR and 541 azoospermic infertile males and 416 fertile controls were genotyped for ERCC2 751A > C using iPLEX Gold Assay. Meta-analyses were performed on XRCC1 399A > G (1022 cases and 1004 controls), ERCC1 C > A 3' UTR (879 cases and 1059 controls), and ERCC2 751A > C (914 cases and 850 controls) polymorphisms to quantitatively estimate the significance of the association between these polymorphisms and the risk of infertility.ResultsStatistically significant association between ERCC2 751A > C SNP and male infertility was found using the codominant model (p = 0.03). Results of meta-analysis suggested a lack of correlation with male infertility risk, which could be due to pooling of studies from different ethnic populations. Due to limited the number of studies, a stratified analysis for different ethnic groups could not be performed.Conclusion (s)In conclusion, AA genotype of 751A > C SNP in ERCC2 correlated with a higher risk of male infertility and may contribute to an increased risk of azoospermia and male infertility in Indian men.

| S-EPMC6338593 | biostudies-literature

Analysis of single-nucleotide polymorphisms in genes associated with triple-negative breast cancer.

Project description:Triple-negative breast cancer (TNBC) is a rare variant of breast cancer (BC) known to be aggressive and refractory. TNBC lacks effective early diagnostic and therapeutic options leading to poorer outcomes. The genomic landscape and alterations leading to BC and TNBC are vast and unclear. Single nucleotide polymorphisms (SNPs) are a widespread form of genetic alterations with a multi-faceted impact on multiple diseases, including BC and TNBC. In this study, we attempted to construct a framework that could identify genes associated with TNBC and screen the SNPs reported in these genes using a set of computational predictors. This framework helped identify BRCA1, BRCA2, EGFR, PIK3CA, PTEN, and TP53 as recurrent genes associated with TNBC. We found 2%-29% of reported SNPs across genes to be typed pathogenic by all the predictors in the framework. We demonstrate that our framework prediction on BC samples identifies 99% of alterations as pathogenic by at least one predictor and 32% as pathogenic by all the predictors. Our framework could be an initial step in developing an early diagnosis of TNBC and potentially help improve the understanding of therapeutic resistance and sensitivity.

| S-EPMC9763624 | biostudies-literature

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