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Background: Androgen deprivation therapy (ADT) resistance is closely associated with altered AR status. Aberrant AR expression is critical for the induction of ADT resistance, necessitating the identification of an anti-PCa target independent of AR expression. Methods: Transcriptomic data and clinical information of PRAD were obtained from TCGA database. Genes with PCa-related and AR expression-independent were screened by bioinformatics, and characterized by PPI and GO functional enrichment analyses. Candidate genes were locked by co-expression correlation and disease-free survival (DFS) analyses. A prognostic gene set was established using LASSO Cox regression algorithm. Cox proportional risk regression was performed to identify a key prognostic gene. Expression of the target protein in PCa tissues was verified by The Human Protein Atlas database. In vitro validation of cellular function and molecular mechanism by knockdown and overexpression of the target gene. Results: Two AR expression-independent genes (SLC43A1 and XRCC3) were available for the optimal prognostic model. This gene set effectively predicted PRAD patients’ DFS at 1-, 3- and 5-year, where XRCC3 and tumor (T) stage were independent risk factors. XRCC3 was higher expressed in PRAD patients with T3-T4 stages and accompanied by poorer DFS. IHC staining also validated its higher expression in high-risk PCa tissues. In vitro experiments demonstrated that silencing XRCC3 significantly inhibited 22Rv1 and DU145 cell proliferation, migration and invasion, while promoted apoptosis. Further, silencing XRCC3 promoted DNA damage-induced p53/Bax signaling pathway activation, which was absent with overexpression. Conclusion: Silencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner. [ABSTRACT FROM AUTHOR]

Objective: Renal cell carcinoma (RCC) is considered as a major type of cancer of the kidney and is estimated to account for about 2-3% of all malignancies in adults. DNA repair mechanisms play a crucial role in defending genomic integrity against DNA damage, and defects in DNA repair mechanisms are associated with cancer susceptibility. The XRCC3 gene plays a pivotal role in the DNA repair system through homologous recombination and chromosomal activity. Therefore, our research aimed to clarify whether XRCC3 Thr241Met polymorphism affects the initiation and progression of RCC. Materials and Methods: This study included 129 patients with RCC and 212 healthy individuals. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to analyze XRCC3 Thr241Met gene polymorphism using SPSS 23 software to facilitate data analysis. Results: Our results revealed no remarkable differences in the genotype and allele frequencies of the Thr241Met polymorphism of XRCC3 between the patient and control groups. However, a greater risk of RCC was reported for the variant (Met/Met) genotype of XRCC3 gene polymorphism, particularly among smokers. Conclusion: Although the XRCC3 Thr241Met polymorphism may not significantly influence RCC initiation and progression in a Turkish population, smoking seems to amplify the risk associated with the (Met/Met) genotype of XRCC3 gene polymorphism. [ABSTRACT FROM AUTHOR]

Abstract Background Prior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer. Methods The comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results The analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70–0.86, P

Background: Prior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer. Methods: The comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results: The analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70–0.86, P < 0.001), homozygote comparison (TT vs. CC: OR = 0.71, 95% CI = 0.58–0.88, P = 0.001), heterozygote comparison (TC vs. CC: OR = 0.67, 95% CI = 0.52–0.87, P = 0.003), and a dominant genetic model (TT/TC vs. CC: OR = 0.68, 95% CI = 0.57–0.81, P < 0.001). Additionally, subgroup analyses based on ethnicity disclosed that these associations were particularly pronounced in the Caucasian population, with all genetic models showing significance (P < 0.05). Conclusions: The XRCC3 Thr241Met polymorphism has been identified as contributing to a reduced risk of pancreatic cancer in the Caucasian population. This finding underscores the need for further research to validate and expand upon our conclusions, emphasizing the urgency for continued investigations in this domain. [ABSTRACT FROM AUTHOR]

Résumé Objectif - En Algérie, le cancer de la prostate (CP) représente un réel problème de santé publique. Notre étude consiste à déterminer l’influence du polymorphisme Thr241Met du gène XRCC3 sur la susceptibilité à développer le CP. Pour cela, nous avons entrepris une étude d’association cas/témoins portant sur ce polymorphisme dans un échantillon de la population de l’Ouest Algérien. Matériels et méthodes - Cette étude a concerné dix sujets atteints de CP et vingt sujets sains non apparentés. L’exploration des différents génotypes du polymorphisme a été réalisée par la technique d’amplification en chaine par polymérase - polymorphisme de longueur des fragments de restriction (PCR-RFLP). La comparaison des fréquences alléliques et génotypiques entre les deux groupes à été établie par le calcul de l’odds ratio (OR) avec un intervalle de confiance à 95%. Résultats - A ce stade de l’étude, l’analyse statistique a montré qu’il n’existait aucune différence statistiquement significative de distribution des fréquences alléliques et génotypiques (OR=0,36 [0,12-1,1] ;P=0,7) de ce polymorphisme exploré entre les cas et les contrôles dans ce premier échantillon de la population explorée. Conclusion - En conclusion, il est envisagé d’augmenter le nombre de cas à étudier pour confirmer cette absence d’association. Par ailleurs, il est important d’explorer d’autres polymorphismes situés non seulement sur le gène XRCC3 mais aussi sur d’autres gènes impliqués dans la réparation de l’ADN, afin de caractériser au mieux sur le plan génétique, le cancer de la prostate dans la population de l’Ouest Algérien. Abstract Objective - In Algeria, prostate cancer (PC) is a real public health problem. Our study consists in determining the influence of the polymorphism Thr241Met of the XRCC3 gene on the susceptibility to develop a PC. To this end, we undertook a case-control study of this polymorphism in a sample of the Algerian West population. Materials and methods - This case-control study involved 10 subjects with PC and 20 unrelated healthy subjects. The various genotypes of the polymorphism were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The comparison of allelic and genotypic frequencies between the two groups was established by calculating the odds ratio (OR) with a 95% confidence interval. Results - In this preliminary exploration, statistical analysis showed that there was no statistically significant difference in the distribution of allelic and genotypic frequencies (OR = 0.36 [0.12-1.1], P = 0.7) of the polymorphism explored between cases and controls in this first sample of the population explored. Conclusion - In conclusion, we consider increasing the size of the sample to be studied to confirm this lack of association. On the other hand, we believe that it is important to explore other polymorphisms located not only on the XRCC3 gene but also on other genes involved in DNA repair in order to enhance genetic characterization of PC in the western Algerian population.

X-ray repair cross-complementing Group 3 (XRCC3) plays an important role in the repair of DNA double-strand breaks. Since it has been reported that breast cancer patients might be deficient in DNA damage repair, previous studies focused on the associations of the XRCC3 Thr241Met polymorphism and breast cancer risk. However, the results are controversial. Hence, we designed this meta-analysis to accurately evaluate the association between an XRCC3 polymorphism and breast cancer. To better understand the association between the rs861539 polymorphism and breast cancer, we performed this comprehensive meta-analysis of 28 852 patients and 30 176 controls. In general, no obvious association was found between the rs861539 polymorphism and breast cancer, but rs861539 was significantly associated with higher breast cancer risk among Asian individuals in a subgroup analysis in all models, especially in the homozygote model (TT vs. CC: OR = 2.142, 95% CI 1.516–3.026). A trend of increased risk of breast cancer was observed based on four other models in addition to the heterozygote model in a mixed population. No association was found between the rs861539 polymorphism and breast cancer in either Caucasian or African individuals. Our meta-analysis proved that the rs861539 polymorphism is closely associated with breast cancer risk in Asian individuals. Further studies should be conducted to confirm our conclusion and explore more associations that may exist between the rs861539 polymorphism and breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Abstract Background Presently, whether X-ray repair cross complementing group 3 (XRCC3) Thr241Met polymorphism is correlated to leukemia risk remains controversial. Because of this reason, the objective of current study is to explore whether XRCC3 Thr241Met polymorphism confers risk to leukemia. Methods Two independent authors systematically and comprehensively searched Pubmed, Embase, the Cochrane library, Google academic, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021. Results Overall, significant associations between leukemia risk and XRCC3 Thr241Met polymorphism were found in Caucasian population by allele contrast (T vs. C: OR 1.20, 95% CI 1.02–1.40), homozygote comparison (TT vs. CC: OR 1.35, 95% CI 1.05–1.73), and recessive genetic model (TT vs. TC/CC: OR 1.31, 95% CI 1.04–1.64). Conclusions The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for leukemia in Caucasian population.

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4; p = 0.01). The −/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT −/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT −/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.

Mona Khyri Alkasaby,1 Abeer Ibrahim Abd El-Fattah,1 Iman Hassan Ibrahim,1 Hesham Samir Abd El-Samie2 1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt; 2Department of Clinical Pathology, Faculty of Medicine (New Damietta), Al-Azhar University, New Damietta, Damietta, EgyptCorrespondence: Iman Hassan IbrahimDepartment of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City 11759, Cairo, EgyptTel +20 1001729242Email imanhassan.pharmg@azhar.edu.egPurpose: Polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and subsequent genetic susceptibility to different cancers. In Egypt, breast cancer is the most common cancer among women, representing 18.9% of the total cancer cases. The present study assesses the correlation between X-ray repair cross-complementing group 3 (XRCC3) polymorphism with breast cancer and treatment response in Egyptian female breast cancer patients.Patients and Methods: This pilot case–control study was conducted on 66 female breast cancer patients and 20 apparently healthy females as a control group. Tumor grading, immunohistostaining of hormone (progesterone and estrogen) receptors and human epidermal growth factor receptor 2 (HER2), and RFLP-PCR for XRCC3 (rs861539) polymorphism were performed. All breast cancer patients received a treatment protocol (after surgery) which was either chemotherapy (anthracyclines followed by paclitaxel or anthracyclines + fluorouracil) or radiotherapy, or both. Disease-free survival (DFS) and overall survival (OS) were recorded.Results: The number of patients with a heterozygous allele (GA) was significantly higher in cases of tumor size > 20 mm. The A allele was correlated with younger age at diagnosis in both chemotherapy and radiotherapy groups. Poor treatment response and higher mortality rates were significantly associated with AA and GA compared with GG alleles (normal allele). In the chemotherapy group, out of eight patients with the A allele, six showed a poor response to treatment containing fluorouracil.Conclusion: XRCC3 rs861539 polymorphism could be associated with lower DFS and OS and poor treatment response. So, we recommend carrying out XRCC3 genotyping before starting treatment to choose the most effective treatment strategy according to XRCC3 polymorphism.Keywords: breast cancer, gene polymorphism, XRCC3, treatment response, survival

Objective - In Algeria, prostate cancer (PC) is a real public health problem. Our study consists in determining the influence of the polymorphism Thr241Met of the XRCC3 gene on the susceptibility to develop a PC. To this end, we undertook a case-control study of this polymorphism in a sample of the Algerian West population. Materials and methods - This case-control study involved 10 subjects with PC and 20 unrelated healthy subjects. The various genotypes of the polymorphism were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The comparison of allelic and genotypic frequencies between the two groups was established by calculating the odds ratio (OR) with a 95% confidence interval. Results - In this preliminary exploration, statistical analysis showed that there was no statistically significant difference in the distribution of allelic and genotypic frequencies (OR = 0.36 [0.12-1.1], P = 0.7) of the polymorphism explored between cases and controls in this first sample of the population explored. Conclusion - In conclusion, we consider increasing the size of the sample to be studied to confirm this lack of association. On the other hand, we believe that it is important to explore other polymorphisms located not only on the XRCC3 gene but also on other genes involved in DNA repair in order to enhance genetic characterization of PC in the western Algerian population.

Jagjeet Kaur, 1 Vasudha Sambyal, 1 Kamlesh Guleria, 1 Neeti Rajan Singh, 2 Manjit Singh Uppal, 2 Mridu Manjari, 3 Meena Sudan 4 1Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, India; 2Department of Surgery; 3Department of Pathology; 4Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, IndiaCorrespondence: Vasudha SambyalDepartment of Human Genetics, Guru Nanak Dev University, Amritsar 143001, Punjab, India Tel +911832258803-09 ext 3448Email vasudhasambyal@yahoo.co.inAim: The X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high.Methods: The present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene–gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression.Results: For XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3– 0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26– 0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27– 0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0– 2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D̍́=0.845, r 2=0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk.Conclusion: XRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.Keywords: XRCC1, XRCC2, XRCC3, polymorphisms, esophageal cancer

Background: Presently, whether X-ray repair cross complementing group 3 (XRCC3) Thr241Met polymorphism is correlated to leukemia risk remains controversial. Because of this reason, the objective of current study is to explore whether XRCC3 Thr241Met polymorphism confers risk to leukemia. Methods: Two independent authors systematically and comprehensively searched Pubmed, Embase, the Cochrane library, Google academic, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021. Results: Overall, significant associations between leukemia risk and XRCC3 Thr241Met polymorphism were found in Caucasian population by allele contrast (T vs. C: OR 1.20, 95% CI 1.02–1.40), homozygote comparison (TT vs. CC: OR 1.35, 95% CI 1.05–1.73), and recessive genetic model (TT vs. TC/CC: OR 1.31, 95% CI 1.04–1.64). Conclusions: The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for leukemia in Caucasian population. [ABSTRACT FROM AUTHOR]

• We have 15 publications with 5,740 cases and 9,931 controls were included in this meta-analysis. • We found that the T allele of the X -ray cross-complementing group 3 protein (XRCC3) Thr241Met polymorphism was significantly associated with an increased risk to gynecological malignancies (GM) in Asians but not in Caucasians. • Our findings indicate that the effect of the XRCC3 Thr241Met polymorphism on the risk of GM is ethnically different and this SNP has its obvious effect on the development of GM in Asians. • There was no meta-analysis about the association between XRCC3 Thr241Met polymorphism and risk of GM until now. Studies have investigated the relationship between the X -ray cross- complementing group 3 (XRCC3) Thr241Met polymorphism and the risk of gynecological malignancies (GM) with the contradictory conclusions. Here, a meta-analysis was performed to provide clear picture of the association between Thr241Met and GM risk. The Pubmed and Chinese National Knowledge Infrastructure (CNKI) databases were searched for published eligible studies. The pooled odds ratios (OR) with their corresponding 95% confidence interval (CI) was used to assessed the strength of association. Totally, 15 publications with 5,740 cases and 9,931 controls were included. In the overall analysis, the results of meta-analysis showed no significant association between the Thr241Met and the risk of GM. However, in the Asians subgroup, significant increased risks were found in the comparisons of TT/CT+TT vs. CC(TT vs. CC: OR=3.25, 95% CI=1.47–7.18; CT+TT vs. CC: OR=1.51, 95%CI=1.10–2.09) in Asians; additionally, stratified analysis by cancer type in Asians, significantly increased risks was found in cervical carcinoma (CT vs. CC: OR=1.50, 95%CI=1.04–2.14; TT vs. CC: OR=3.14, 95%CI=1.38–7.14; CT+TT vs. CC: OR=1.64, 95% CI=1.17–2.31). It suggests that the risk of GM might be significantly increased by the XRCC3 Thr241Met polymorphism according to ethnicity and cancer types. Further studies with larger sample size in different ethnic populations and different sites of GM are needed to verify the findings. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelialcarcinoma of the bladder (UCB). This study focused on three specific SNPs in a population withhigh exposure to environmental carcinogens including tobacco and alcohol. A case-control studydesign was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751GlnDNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. Onehundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotypewas associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4;p= 0.01). The−/+and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus singletumors (p= 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, andrisk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25;p< 0.01)and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41;p< 0.01) conferred a protective effect againstdeveloping UCB. The XPC PAT−/+ and XRCC3 Thr241Met SNPs are associated with predispositionto UCB. The XPC PAT−/+ SNP is also an indicator of bladder tumor multiplicity, which mightrequire a more individualized surveillance and treatment. [ABSTRACT FROM AUTHOR]

Jen-Sheng Pei,1,* Wen-Shin Chang,2,* Pei-Chen Hsu,1,* Chao-Chun Chen,1 Shun-Ping Cheng,3 Yun-Chi Wang,2 Chia-Wen Tsai,2,* Te-Chun Shen,2,4,* Da-Tian Bau2,5,6,* 1Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, Republic of China; 2Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan, Republic of China; 3Department of Physical Medicine and Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, Republic of China; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China; 5Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, Republic of China; 6Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, Republic of China *These authors contributed equally to this work Purpose: A growing body of evidence shows an association between DNA repair protein genotypes and susceptibility to various cancers. However, few studies have assessed the contribution of the genotype of XRCC3, a homologous repair gene, to the occurrence or prognosis of childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the contribution of seven XRCC3 polymorphisms to childhood ALL.Patients and methods: We recruited 266 patients with childhood ALL and 266 healthy controls. Genomic DNA was isolated from peripheral blood samples. The XRCC3 rs1799794, rs45603942, rs1799796, rs861530, rs28903081, rs861539, and rs3212057 polymorphic genotypes of each subject were determined through conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.Results: Genotypes with the rs861539 polymorphism were significantly associated with the risk of childhood ALL. The allelic distribution analyses suggested a significant association between the T allele at rs861539 with an increased risk of childhood ALL in the Taiwanese population. Polymorphic variants of XRCC3 at rs3212057 or rs28903081 did not exist in the study population. XRCC3 rs1799794, rs45603942, rs1799796, and rs861530 were not significantly associated with the risk of childhood ALL in the Taiwanese population.Conclusion: Our findings suggest that XRCC3 genotypes with polymorphisms at rs861539 may play a role in determining individual susceptibility to childhood ALL in this Taiwanese population. The polymorphism may be a potential detector and predictor of childhood ALL. Keywords: acute lymphoblastic leukemia, ALL, childhood, genotype XRCC3, polymorphism, Taiwan

Chronic hepatitis C (CHC) is a worldwide etiology of chronic hepatic insult particularly in Egypt. DNA‐repair systems are responsible for maintaining genomic integrity by countering threats posed by DNA lesions. Deficiency in the repair capacity due to genetic alterations in DNA‐repair genes can lead to genomic instability and increased risk of cancer development. The present work aimed at studying the possible association between XRCC1‐G28152A (rs25487), XRCC3‐C18067T (rs861539), and XRCC7‐G6721T (rs7003908) single nucleotide polymorphisms (SNPs) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. The study was conducted on 100 newly diagnosed HCC patients and 100 age‐ and sex‐matched healthy controls. Laboratory workup revealed that all HCC patients have chronic hepatitis C viral infection. Genotyping of the studied SNPs was performed by real‐time PCR. The heteromutant genotype of XRCC1 (GA) conferred an almost two‐fold increased risk of HCC (OR , 2.35; 95% CI, 1.33‐4.04). Regarding XRCC7, the heteromutant (TG) genotype conferred a two‐fold increased risk of HCC (OR , 2.17; 95% CI, 1.23‐3.82). Coinheritance of the polymorphic genotypes of XRCC1 and 7 was significantly higher in HCC cases than controls and was associated with an 11‐fold increased risk of HCC (OR , 11.66; 95% CI, 2.77‐49.13). The frequency of XRCC3 polymorphic genotypes in HCC patients was close to that of the controls. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms in DNA repair genes, XRCC1 (Arg399Gln) and XRCC3 (Thr241Met), may affect their DNA repair capacity leading to individual variation in breast cancer susceptibility among Bangladeshi females. Methods: The case–control study comprised 121 breast cancer patients and 133 healthy controls. Genomic DNA isolated from peripheral blood was genotyped for target SNPs using PCR-RFLP method. Results: For XRCC1, heterozygous Arg/Gln and homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0084 to 3.1442, p = 0.0467) and 2.41-fold (95% CI 1.0354 to 5.5914, p = 0.0413) increased risk of breast cancer, respectively, when compared with Arg/Arg genotype. The presence of any XRCC1 Gln showed association with 1.93-fold increased risk. The variant Gln allele was associated with increased risk of breast cancer (95% CI 1.1885 to 2.6805, p = 0.0052). For XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were associated with 1.85-fold (95% CI 1.0815 to 3.1834, p = 0.0248) and 1.89-fold (95% CI 1.1199 to 3.1908, p = 0.0171) higher risk, respectively, compared to Thr/Thr genotypes. The variant Met allele showed significant association with increased breast cancer susceptibility. Among cases genotype frequencies were significantly different in patients with age 55 or above, and with menopause and diabetes. Conclusion: XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms may be associated with increased breast cancer risk in Bangladeshi females. [ABSTRACT FROM AUTHOR]

Abstract Background: Biological and epidemiological data suggest that damage induced by endogenous and exogenous factors affects the integrity and stability of DNA and associated with susceptibility to breast cancer. The XRCC3 protein participates in DNA double-strand breaks and recombination repair. The aim of the present study was to evaluate associations between the risk of breast cancer and Thr241Met polymorphism in the XRCC3 gene. Materials and Methods: In this study, the effects of Thr241Met polymorphism of the XRCC3 gene and the risk of breast cancer in a population-based case-control study inclusive 80 patients and 80 healthy individuals of women in Markazi province were evaluated. Genomic DNA was extracted from blood samples using the kit procedure. The genotypes of samples were determined by PCR-RFLP technique. Statistical analysis was done using SPSS software (estimation of χ2 and p-value) and the final results were determined. Results: Statistically significant difference was observed between the two groups of patients and controls for three genotypes of the site rs861539 (p= 0.000). Genotype CT (p= 0.000, OR=2.352, CI= 95%; 2.431 - 39.948) and TT (p = 0.003, OR= 2.352, CI=95%; 0.611 - 9.049) significant associations were showed with risk of breast cancer. Instead, the genotype CC (p= 0.000) showed a protective role against susceptibility to breast cancer. Conclusion: This study identified that there is significant association between Thr241Met polymorphisms of the XRCC3 and the risk of susceptibility to breast cancer, which is in accordance to some of researchers' studies.

Background and Aim: Gastrointestinal (GI) cancer presents a significant worldwide health burden, influenced by a combination of genetic and environmental factors. This study endeavors to explore the combined effects of the XRCC1 , XRCC2 , XRCC3 , and TP53 genes that contribute to the heightened risk of GI cancer, shedding light on their combined influence on cancer susceptibility., Materials and Methods: A total of 200 histologically confirmed cases of GI cancer and an equal number of controls were selected to examine genetic polymorphisms within the XRCC1 , XRCC2 , XRCC3 , and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05)., Results: Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004), Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population., Conclusions: The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1 , XRCC2 , and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institute Ethics Committee of Krishna Institute of Medical Sciences issued approval KIMSDU/IEC/164/2017-2018 dated July 1, 2018. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Datkhile et al.)

Capacity for DNA repair is essential in maintaining human cellular functions and homeostasis. Repair capacity can be altered by XRCC3 gene polymorphisms that affect an individual’s susceptibility to carcinogenesis. The present study aimed to investigate the potential association between the XRCC3 C722T (rs861539) gene polymorphism and the risk of head and neck squamous cell carcinoma (HNSCC) in an Indonesian population. Using the polymerase chain reaction-restriction fragment length polymorphism method, the genomic DNA of 81 patients with oral squamous cell carcinoma and 95 healthy control participants was genotyped to identify the status of XRCC3 C722T polymorphism. For statistical analysis, chi-square test was applied. The TT genotype and T allele of the XRCC3 C722T polymorphism was significantly associated with the risk of HNSCC (P=0.001). The C722T (rs861539) polymorphism of the XRCC3 gene may be associated with the risk of HNSCC. Moreover, this polymorphism might be used as a predictive indicator of precancerous lesions and HNSCC in an Indonesian population. [ABSTRACT FROM AUTHOR]

Background: DNA repair genes play a key role in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as X-ray repair cross-complementing group 1 and 3 genes (XRCC1 and XRCC3), are implicated to contribute to carcinogenesis.

Background/Aims: DNA HRR pathway and BER pathway play vital roles in differentiated thyroid cancer (DTC) development, thus we supposed that polymorphisms of XRCC1, XRCC2, XRCC3 DNA repair genes are associated with thyroid cancer risk and progression. Methods: We searched the NCBI database for relevant literatures to determine eight SNPs to be included in our study (XRCC1: rs25487, rs25489, rs1799782; XRCC2: rs3218536; XRCC3: rs1799794, rs56377012, rs1799796, rs861539). Results: SNP of rs25487 was linked with a 53% decrease in DTC risk (OR: 0.47; 95%CI: 0.268-0.82; P = 0.01). For SNP of rs1799782, the homozygous TT genotype indicated a statistically significant 2-fold increased risk of DTC (OR: 2.09; 95%CI: 1.27-3.43; P P P = 0.02) after multivariate adjustment. Similar results for most of the SNPs were obtained from subgroup analysis by different histological types of DTC. Haplotype analysis revealed that AGC and GGT haplotypes of XRCC1 polymorphisms were associated with DTC. Moreover, results from gene-gene interaction showed that XRCC1-rs25487, XRCC1- rs1799782 and XRCC3- rs861539 variants jointly contributed to a specifically increased risk of DTC, with the combination variant of rs1799782-CT heterozygote and rs861539-TT homozygote exhibiting a higher 3.66-fold risk of DTC (OR: 3.66; 95% CI: 1.476-9.091, P = 0.005). Conclusion: Polymorphisms of XRCC1 (rs25487, rs1799782) and XRCC3 (rs861539), may play a critical role in DTC development and progression. Furthermore, XRCC1 variant can interact with XRCC3 variant to significantly increase DTC susceptibility. Identifying these genetic risk markers could provide evidence for exploring the insight pathogenesis and develop novel therapeutic strategies for DTC.

Background: This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance. Subjects and Methods: SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene–gene (GxG) interaction and gene–environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi‐square test, and univariate and multivariate methods were applied for survival analyses. Results: Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers. Conclusion: Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development. [ABSTRACT FROM AUTHOR]

The studied the frequency distribution of the genotypes genes of the excision repair of bases and nucleotides: XPD (rs13181, rs799793), ERCC1 (rs11615), XRCC3 (rs861539) and XRCC1 (rs25487) among workers of hazardous and harmful industries (miners and workers of asbestos cement plants (n=214) to identify markers of risk of bronchopulmonary pathology. In 90 patients with bronchopulmonary pathology and 124 persons working under the same conditions but without respiratory system diseases, the polymerase chain reaction in real time was determined by the polymorphisms of DNA repair genes: XPD (rs13181, rs799793), ERCC1 (rs11615), XRCC1 ( rs25487) and XRCC3 (rs861539). As a result of the study, the genotypes associated with the risk of developing bronchopulmonary pathology were as follows: XPD⋅C/C (rs13181) (P≤0.04, x² = 4.11; OR = 2.13; 95% CI: 0.96-4.78), XRCC1•A/A (rs25487) (P≤0.009, x² = 6.73, OR = 3.31, 95% CI: 1.20-9.47). We have determined certain genotypes that may contribute to resistance to the development of these diseases: XPD•A/C (rs13181) (P≤0.03, x² = 4.48; OR = 0.55; 95% CI: 0.30- 0.99), XRCC1•G/A (rs25487) (P≤0.04, x² = 4.16; OR = 0.56; 95% CI: 0.31-1.02). The obtained results for indicate the importance of polymorphisms of DNA repair genes in the formation of bronchopulmonary pathology of certain professional groups, which opens the prospects for the development of modern preventive measures. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most frequent and aggressive form of high-grade malignant glioma. Due to the dismal prognosis faced by patients suffering from this disease, there is a need for identifying new targets that might improve therapy. The aim of this study was to determine the contribution of the DNA double-strand break (DSB) repair protein X-ray repair cross-complementing 3 (XRCC3) to the resistance of glioma cells to the chemotherapeutic drug temozolomide. Analysis of a publicly available database, E-GEOD-4290, showed that gliomas overexpress XRCC3 (NM_005432) compared to normal brain tissue. Using an isogenic glioma cell system, in which XRCC3 was downregulated by interference RNA, we demonstrate that XRCC3 protects glioma cells against temozolomide-induced reproductive cell death, apoptosis and cell cycle inhibition. Furthermore, XRCC3 knockdown significantly reduced the rate of repair of DSBs following TMZ treatment, which results in increased drug sensitivity. This study confirms the importance of homologous recombination in the resistance of glioma cells to the methylating drug temozolomide and adds XRCC3 to the list of homology-directed DNA repair proteins as possible targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported. Methods: An extensive panel of five polymorphisms on four candidate genes (ABCB1, CYP2C8*3, CYP3A4*1B, XRCC3), previously validated as significant markers related to paclitaxel and Docetaxel toxicity, are analyzed and discussed. We genotyped 76 cancer patients, and 35 of them received paclitaxel or docetaxel-based therapy. What is more, an early outline evaluation of the genotyping costs and benefit was assessed. Results: Out of 35 patients treated with a taxane, six (17.1%) had adverse neuropathy events. Pharmacogenomics analysis showed no correlation between candidate gene polymorphisms and toxicity, except for the XRCC3 AG+GG allele [OR 2.61 (95% CI: 0.91-7.61)] which showed a weak significant trend of risk of neurotoxicities vs. the AG allele [OR 1.52 (95% CI: 0.51-4.91)] P = 0.03. Summary: Based on our experimental results and data from the literature, we propose a useful and low-cost genotyping panel assay for the prevention of toxicity in patients undergoing taxane-based therapy. With the individual pharmacogenomics profile, clinicians will have additional information to plan the better treatment for their patients to minimize toxicity and maximize benefits, including determining cost-effectiveness for national healthcare sustainability. [ABSTRACT FROM AUTHOR]

DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population.

Background: At present very little information is available on combined effects of DNA repair genes with tumor suppressor gene polymorphisms and their association with cancer susceptibility. No such association studies have been carried out with breast cancer or any other cancer from India. Present study was conducted to study the combined effects of SNPs of XRCC1, XRCC2, XRCC3 with Arg72Pro and Arg249Ser SNPs of TP53 gene in risk of BC in rural parts of India., Methods: The polymorphisms of Arg194Trp, Arg280His, Arg399Gln of XRCC1, Arg188His of XRCC2 and Thr241Met of  XRCC3 with Arg72Pro and Arg249Ser of TP53 gene polymorphisms was studied by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. The association among the polymorphisms with breast cancer risk was studied by Odds ratio within 95% confidence interval and SNP-SNP interaction were confirmed by logistic regression analysis., Results: The results of genotype frequency distribution of XRCC1, XRCC2, XRCC3 genotypes showed positive association between XRCC1 Arg280His polymorphism and BC risk (OR=4.54; 95% CI: 3.36- 6.15; p<0.0001).  Also the heterozygous genotypes Arg188His of XRCC2 (OR=1.58; 95% CI: 1.13- 2.21; p=0.007) and Thr241Met genotype of XRCC3 (OR=2.13; 95% CI: 1.44- 3.13; p=0.0001) were associated with BC risk. The combination of heterozygous Arg280His genotype of XRCC1 along with Arg72Pro genotype of TP53 increased the risk of BC (OR=4.53; 95% CI: 2.85-7.20); p<0.0001). Similarly,  the combined effect of heterozygous Arg/His genotype of XRCC1 with heterozygous Arg/Ser genotype of TP53 at codon 249 showed significant association with increased BC risk (OR=5.08; 95% CI: 2.86-9.04); p<0.0001)., Conclusion: The findings derived from our study concluded that the heterozygous variant Arg280His genotype of XRCC1 and Thr241Met polymorphism of XRCC3 in combination with heterozygous arginine72proline genotype and heterozygous Arg249Ser polymorphism of TP53 showed significant association with breast cancer risk in Maharashtrian women.

Background: DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, RAD51 rs1801320, XRCC1 rs25487, XRCC2 rs3218536, and XRCC3 rs861539 with the risk of breast cancer. Materials and Methods: In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. Results: The GC genotype ( p  = 0.018) and the combined GC+CC ( p  = 0.03) genotypes of RAD51 rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype ( p  = 0.0001), the combined CT+TT genotypes ( p  = 0.0002), and the T allele ( p  = 0.0019) of XRCC3 rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of XRCC1 rs25487 and XRCC2 rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between XRCC3 and XRCC2 . String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. Conclusion: RAD51 rs1801320 and XRCC3 rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among XRCC1 , XRCC2 , XRCC3 , and RAD51 .

The X-ray repair cross-complementing group 3 ( XRCC3) Thr241Met polymorphism (rs861539, C > T) has drawn wide attentions as its association with cancer risk and its involvement in DNA repair. Several studies have attempted to link rs861539 to nasopharyngeal cancer (NPC) risk; however, the sample sizes of these studies are small and the results are controversial. To investigate the relationship of rs861539 and NPC susceptibility, we conducted a large-scale case-control study involving 4001 NPC cases and 2967 controls of southern Chinese. Logistic regression analysis revealed significant association for rs861539 and NPC risk under the recessive model (TT vs. CT + CC) with adjustment of age and gender (odds ratio, OR = 2.72; 95 % CI 1.10-6.72; P = 0.03). Further, meta-analysis involving 4457 NPC cases and 4132 controls from four studies showed consistent association of TT carriers and NPC risk ( OR = 3.12; 95 % CI 1.58-6.13; P = 0.001). Taken together, our findings based on large-scale sample size suggested rs861539 at XRCC3 to be associated with NPC risk through recessive model. [ABSTRACT FROM AUTHOR]

MicroRNAs are small non-coding RNAs with 18–22 nucleotides in length and have been proposed to function in various biological processes by targeting genes for post-transcriptional degradation via their 3′ untranslated region. Moreover, they have been suggested to improve the chemosensitivity in a panel of tumors. However, the biological functions of microRNA-127-3p in esophageal carcinogenesis are still enigmatic. Thus, in the study, we firstly analyzed the roles of microRNA-127-3p in regulating the growth of esophageal cancer cells both in vitro and in vivo . Afterwards, using the microRNA-targeted gene prediction software and the dual-luciferase reporter assays, we confirmed that microRNA-127-3p specifically reduced the expression of X-ray repair complementing defective repair in Chinese hamster cells 3, one of RAD51 recombinase paralogs, at both mRNA and protein levels. Furthermore, using the homologous recombination repair and non-homologous end joining repair reporter systems, we found that microRNA-127-3p specifically compromised the homologous recombination repair and significantly increased DNA double strand breaks in cells. Besides, it statistically increased the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivative in vivo by mechanistically impairing the recruitment of RAD51 to the damage sites. In summary, our findings not only suggest that microRNA-127-3p can be used as a predictor for evaluating the development of esophageal carcinoma, but also show that it can be used to increase the chemosensitivity of esophageal cancer patients to the phenanthroline-dione derivative, which might be a potential anticancer candidate in the future. [ABSTRACT FROM AUTHOR]

The variability, perceived in DNA repair genes, may be of clinical importance for evaluation of the risk of occurrence of a given type of cancer, its prophylactics and therapy. The aim of the present work was to evaluate associations between the risk of ovarian cancer and polymorphisms in the genes, encoding for two key proteins of homologous recombination: XRCC2 Arg188His (c. 563 G > A; rs3218536) and XRCC3 Thr241Met (c. 722 C > T; rs861539). The study consisted of 700 patients with ovarian cancer and 700 healthy subjects. Analysis of the gene polymorphisms was performed using PCR-RFLP (restriction length fragment polymorphism). We found a statistically significant increase of the 188His allele frequency (OR = 4.01; 95% CI = 3.40–4.72; p < .0001) of XRCC2 in ovarian cancer compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the XRCC3 Thr241Met polymorphism between patient and control groups. Association of these genetic polymorphisms with histological grading showed increased XRCC2 188Arg/His (OR = 33.0; 95% CI = 14.51–75.05; p < .0001) and 188His/His genotypes (OR = 9.37; 95% CI = 4.79–18.32; p < .0001) and XRCC3 241Thr/Met (OR = 24.28; 95% CI = 12.38–47.61; p < .0001) and 241Met/Met genotype frequencies (OR = 17.00; 95% CI = 8.42–34.28; p < .0001) in grading 1 (G1) as well as 188His (OR = 2.78; 95% CI = 2.11–3.69; p < .0001) and 241Met allele overrepresentation (OR = 2.59; 95% CI = 2.08–3.22; p < .0001) in G1 ovarian patients. Finally, with clinical FIGO staging under evaluation, an increase in XRCC2 188His/His homozygote and 188Arg/His heterozygote frequencies in staging I (SI) and XRCC3 Thr/Met heterozygote frequencies in SI was observed. The obtained results indicate that XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be positively associated with the incidence of ovarian carcinoma in the population of Polish women. [ABSTRACT FROM AUTHOR]

In several DNA repair genes, polymorphisms may result in reduced repair capacity, which has been implicated as a risk factor for various types of cancer. The frequency of the polymorphic alleles varies among populations, suggesting an ethnic distribution of genotypes. We genotyped 300 healthy Southeastern Brazilian individuals (262 of European ancestry and 38 of African ancestry) for polymorphisms of codons 194 and 399 of the XRCC1 base excision repair pathway gene and of codon 241 of the XRCC3 homologous recombination repair pathway gene. The allele frequencies were 0.07 for the Arg194Trp and 0.33 for the Arg399Gln codons of the XRCC1 gene and 0.35 for the Thr241Met codon of the XRCC3 gene. The genotypic frequencies were within Hardy-Weinberg equilibrium. These frequencies showed ethnic variability when compared with those obtained for different populations from several countries.