Ethnicity-stratified analysis of the association between XRCC3 Thr241Met polymorphism and leukemia: an updated meta-analysis

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.

Title: Association of XRCC3, XRCC4, BAX and BCL-2 Polymorphisms with the Risk of Breast Cancer

Background Breast cancer is the most common malignancy in women. Genetic risk factors associated with breast cancer incidence have been identified. Aims The aim of this study was to determine the association of XRCC3 Thr241Met (rs861539), XRCC4 G(-1394)T (rs6869366) DNA repair and BAX G(-248)A (rs4645878), BCL2 C(-938)A (rs2279115) apoptotic gene polymorphisms with breast cancer. Materials and Methods Genetic analysis was performed using peripheral blood samples. Gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 175 patients and 158 healthy controls were enrolled in the study. Results Breast cancer risk was 5.43 times more in individuals with AA genotype of Bax G(-248)A (rs4645878) (p = 0.002). The risk of metastasis was 11 times with this genotype. It was associated with 6 times more risk of having a tumor larger than 2 cm. The risk of breast cancer was 2.77 times more in individuals carrying the Met/Met genotype of XRCC3 Thr241Met (rs861539) (p = 0.009). The risk of having advanced clinical stage (stage III + IV) with the Met/Met genotype was 4 times more increased. No relationship with breast cancer was found with XRCC4 G(-1394)T (rs6869366) and BCL2 C(− 938)A(rs2279115) gene polymorphisms. Conclusion Multi-center trials using subjects with genetic variations are needed to establish the relationship between breast cancer and single gene polymorphism.

ANALYSIS OF XENOBIOTIC DETOXIFICATION AND DNA-REPAIR GENES IN POPULATIONS LIVING IN PESTICIDE CONTAMINATED AREAS

Проведена оценка риска влияния многолетней пестицидной загрязненности окружающей среды на генетический статус населения, проживающего в 5 населенных пунктах Талгарского района (пп. Кызылкайрат, Бескайнар, Бельбулак, Амангельды, Енбекши) Алматинской области, где располагаются неутилизированные, запрещенные к использованию пестициды класса СОЗ. Результаты цитогенетического анализа населения, подверженного действию пестицидов, выявили высокую частоту хромосомных аберраций, превышающую контрольные показатели от 2,2 до 3,6 раз. Молекулярно-генетический анализ выявил повышенную частоту нефункциональных аллелей глутатион-S-трансфераз M1 и Т1 типов, что может оказывать влияние на снижение функций детоксикации ксенобиотиков у обследованного населения. Определена достоверная ассоциативная связь полиморфизма гена репарации ДНК XRCC3 Thr241Met, с повышенной частотой хромосомных аберраций у населения, проживающего вблизи очагов пестицидного загрязнения. The risk assessment of the impact of long-term pesticide pollution of the environment on the genetic status of the population living in 5 settlements of the Talgar district (Kyzylkairat, Beskaynar, Belbulak, Amangeldy, Enbekshi) of Almaty region, where unused, banned for use POPs pesticides are located, has been carried out. The results of cytogenetic analysis of the population exposed to pesticides revealed a high frequency of chromosomal aberrations, exceeding the control values from 2.2 to 3.6 times. Molecular genetic analysis revealed an increased frequency of non-functional alleles of glutathione-S-transferases of M1 and T1 types, which may affect a decrease in the functions of detoxification of xenobiotics in the surveyed population. A reliable associative relationship of the XRCC3 Thr241Met DNA repair gene polymorphism with an increased frequency of chromosomal aberrations in the population living near foci of pesticide contamination was determined.

DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European 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.

An updated quantitative evaluation of the association between leukaemia risk and XRCC3 Thr241Met polymorphism

IntroductionSeveral analyses have been conducted to assess the association between leukaemia risk and XRCC3 Thr241Met polymorphism. However, their results are conflicting. Hence, this comprehensive study was carried out to obtain a more accurate assessment of the association between leukaemia risk and XRCC3 Thr241Met (rs861539) polymorphismMaterial and methodsWe searched Ovid, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Google Scholar, PubMed database and Excerpta Medica Database (EMBASE) for potential eligible studies published as of July 2020. Pooled odds ratio (OR) and 95% confidence interval (ci) were used in evaluating the strength of the association between Thr241Met polymorphism of XRCC3 and leukaemia, and the p-value less than 0.05 (p < 0.05) was considered as the level of significance.ResultsA total of 17 studies consisting of 7241 controls and 4198 cases met our inclusion criteria. No significant association was observed between leukaemia risk and Thr241Met polymorphism of XRCC3 across the five genetic variants. In our ethnicity subgroup evaluation, we noted a significant association between leukaemia risk and Thr241Met polymorphism of XRCC3 among Caucasians under four genetic models. Furthermore, SNP (rs861539) of XRCC3 has a protective effect among Asians under four genetic models.ConclusionsThr241Met polymorphism of XRCC3 has a protective effect in the Asian population but has oncogenic potential in the Caucasian population.

Evaluation of the ERCC2 (Lys751Gln), MSH2 (gIVS12-6TC), RAD54 (Ala730Ala), XPC (Lys939Gln), XPG (Asp1104Hist), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms in the Ecuadorian population with retinoblastoma

Background Retinoblastoma is a neoplasia that starts in the retina and may have inheritable or sporadic genetic predisposition. This affects children, mainly those who are under 5 years old. Approximately 9,000 new cases are diagnosed per year worldwide. In Ecuador this disease has an incidence of 1 per each 20,000 live births. The genetic predisposition to develop retinoblastoma is strongly influenced by RB1 gene, and may be influenced by the presence of genetic polymorphisms which intervene in the DNA repair system. Methods This study has analyzed the genotype frequency of ERCC2 (Lys751Gln), MSH2 (gIVS12-6TC), RAD54 (Ala730Ala), XPC (Lys939Gln), XPG (Asp1104Hist), XRCC1 (Arg399Gln), and XRCC3 (Thr241Met) polymorphisms of different repair genes, genotyping 90 individuals affected with retinoblastoma and 80 healthy individuals through polymerase chain reaction / restriction fragments length polymorphism and sequencing analysis. Results The presence of the (C/C) mutant homozygous genotype of XPC (Lys939Gln) polymorphism triggers a significant risk of developing retinoblastoma with an odds ratio (OR) of 3 (CI: 1.22-9.84; p < 0.05). Likewise, the A/G heterozygous genotype and the combination A/G+G/G of XRCC1 (Arg399Gln) polymorphism presented ORs of 9.7 (CI: 4.45-21.08; p < 0.001) and 7.55 (IC: 3.57-16; p < 0.001), respectively. Conclusions The genetic variants XPC (Lys939Gln) and XRCC1 (Arg399Gln) may be associated with the risk of developing retinoblastoma in the Ecuadorian population.