Association between XRCC3 rs861539(Thr241Met) polymorphism and thyroid cancer risk (a Meta-analysis)

Objective To explore the association between single nucleotide polymorphism (SNP) in the XRCC3 rs861539(Thr241Met) locus and thyroid cancer risk. Methods Studies investigating the association between SNP in the XRCC3 gene and thyroid cancer susceptibility were retrieved from the PubMed, Embase, Web of Science, CNKI (Chinese National Knowledge Infrastructure), WanFang, and CBM (China Biology Medicine) databases. Eligible studies were screened according to inclusion/exclusion criteria and principles of quality evaluation. Meta-analysis was performed using Stata 14.0 software. Odds ratios with their corresponding 95% confidence intervals were pooled to assess the association between SNP in the XRCC3 gene rs861539 locus and thyroid cancer susceptibility. Results 10 articles(11 studies) were eligible for this meta-analysis. Meta-analysis results were shown as follows: No significant association was found between XRCC3 rs861539 polymorphism and thyroid cancer risk in Dominant and Overdominant models〔Dominant model: CT+TT vs CC, OR=1.231, 95% CI(0.998, 1.474); Overdominant model: CT vs TT+CC, OR=1.05, 95% CI(0.94, 1.18)〕. Significant associations were found in Recessive and Allelic models〔Recessive model: TT vs CC+CT, OR=1.632, 95% CI(1.349, 1.974); Allelic model: T vs C: OR=1.263, 95% CI(1.091, 1.462)〕. Conclusion The results of this study suggest that the XRCC3 rs861539(Thr241Met) polymorphism may be associated with an increased thyroid cancer risk in overall population, and a tendency for significantly increased thyroid cancer risk in TT(Met/Met) genotype population.

Single nucleotide polymorphism rs1799794 in XRCC3 gene on breast cancer patients

The single nucleotide polymorphisms of the XRCC3 gene including rs1799794 affect the DNA double-strand break/repair. Therefore, it plays a critical part in the initiation of carcinogenesis. This study aimed to investigate the distribution of rs1799794 and the association between rs1799794 and breast cancer risk. The study was performed in 208 Vietnamese females suffering from breast cancer and 208 age-matched normal healthy controls. DNA was extracted from whole blood whilst genotyping was conducted using PCR-RFLP. The results show that the frequency of the A and G allele in the case group are 0.575 and 0.425, in the control group are 0.548 and 0.452. The frequency of AA, AG, GG genotype in the case group are 34.6, 45.7, and 19.7%; in the control group are 33.2, 43.3, and 23.5%. AG genotype of rs1799794 associated with disease onset early of breast cancer, increasing the risk of breast cancer among those who were 45 years old and younger. The GG genotype has protective effects and reduces the risk of breast cancer in the age group ≤45 years.

Polymorphisms and Mutations in GSTP1, RAD51, XRCC1 and XRCC3 Genes in Breast Cancer Patients

Background Genotoxic factors, including ionizing radiation and oxidative stress, are associated with genomic instability and development of breast cancer (BC). The homologous recombination DNA repair (HRR) pathway, base excision repair (BER) mechanism, and antioxidative enzymes are required as defense mechanisms against these DNA damaging agents. GSTP1, XRCC1, XRCC3 and RAD51 proteins are essential components of antioxidation, BER and HRR of DNA, respectively. Deficiencies in BER, HRR and antioxidation pathways are involved in the progression of cancer. Methods Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and blood samples of BC patients of an Italian population. Genomic DNA was also extracted from blood specimens of a control group. DNA sequencing was performed for six single-nucleotide polymorphisms (SNPs) in the GSTP1, RAD51, XRCC1 and XRCC3 genes in BC patients and the control group. Results Two variants in the 5′-UTR of the XRCC3 (rs1799794 A/G) and RAD51 (rs1801321) genes showed a significant association with susceptibility to BC (OR = 4.125; 95% CI 1.057-16.102; p = 0.03 and OR = 2.04; 95% CI 0.4925-8.449; p = 0.007, respectively). Additionally, we reported 2 mutations in intron 7 of the XRCC3 gene, CTdel (rs543072564) and A/G (rs369703243). Conclusions Our results underscored the existence of an association between XRCC3-5′-UTR-A/G (rs1799794) and RAD51-5′-UTR G172T (rs1801321) genotypes and BC risk in an Italian population. The presence of mutations in the intronic region of the XRCC3 gene highlights the importance of more sequence screening of DNA repair genes for possible genetic penetrance in BC.

Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer

Background/Aims: In mammalian cells, XRCC3 plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to thyroid cancer. In this study, we used a haplotype-based approach to investigate whether 5 selected SNPs i.e. rs1799796, rs1799794, rs861539, rs709399 and rs861530 of XRCC3 gene are associated with thyroid cancer risk in 456 cancer patients and 400 cancer-free controls. Methods: Genotyping was performed using Allele-specific PCR followed by sequencing. Statistical analysis was performed to analyse gene and haplotype association. Results: After analysis, frequency of mutant genotype/alleles of SNPs (rs1799796, p<0.0001; rs1799794, p<0.0001; rs861539, p<0.001; rs709399, p <0.0001; rs861530, p<0.002) was found significantly higher in thyroid cancer patients compared to controls. Significant associations were found for most of the variant genotypes in SNPs of rs1799794, rs1799796, rs861539, rs861530 and rs709399 in papillary thyroid and follicular cancer patients compared to other histologic subtypes of thyroid carcinoma. Additionally, haplotype analysis revealed that haplotypes, AACGA (p= 0.0005), AGTAA (p= 0.008), GATAA (p= 0.001), GGCAA (p= 0.001) were linked with significant increase in thyroid cancer risk. However, haplotype AGCGG (p= 0.0009) was associated with a significant reduced thyroid cancer risk. Conclusion: Our results suggest that common genetic variants in the XRCC3 gene of DSBR pathway may modulate thyroid cancer risk.