Single nucleotide polymorphisms in the homologous recombination repair genes and breast cancer risk in Polish women.

Genetic polymorphisms in homologous recombination repair genes that can lead to protein haploinsufficiency are generally associated with increased cancer risk. The aim of the present study was to evaluate associations between the risk of breast cancer and single nucleotide polymorphisms in the genes, encoding three key proteins of the homologous recombination repair: RAD51 (the human homologue of the E. coli RecA protein), X-ray repair cross-complementing group (XRCC) 2 and XRCC3. The polymorphisms studied were G135C of the RAD51 gene (c. -98 G>C; rs1801320), Arg188His of the XRCC2 gene (c. 563 G>A; rs3218536), and Thr241Met of the XRCC3 gene (c. 722 C>T; rs861539). Each polymorphism was genotyped by the PCR-RFLP (restriction fragment-length polymorphism) method in 700 Polish female patients with sporadic breast cancer and in 708 cancer-free women, who served as controls. In the present study, we showed the association between RAD51 G135C polymorphism and the incidence of breast cancer (p < 0.0001), but found no significant association with XRCC2 Arg188His or XRCC3 Thr241Met polymorphism. Instead, significant association was identified between XRCC2 Arg188His or XRCC3 Thr241Met polymorphism and breast cancer progression, assessed by the histological grading. However, each of these three polymorphisms was not associated with the tumor size or the lymph node metastases. This study provides evidence that links single nucleotide polymorphisms of RAD51 and XRCC2/3 genes with the risk of breast cancer in Polish women. In conclusion, RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of sporadic breast cancer in female population.

Analysis of the polymorphisms in non-homologous DNA end joining (NHEJ) gene Ku70 and Ligase IV in sporadic breast cancer in women.

PURPOSE: Breast cancer is one of the major killers worldwide. Aberrant double-stranded break (DSB) repair leads to genomic instability, which is a hallmark of malignant cells. Double-stranded breaks are repaired in two pathways: homologous recombination (HR) and non-homologous DNA end joining (NHEJ). It is not known whether these repair pathways are affected in sporadic breast tumours. MATERIAL AND METHODS: In the present work the distribution of genotypes and frequency of alleles of the Ku70, A46922G (rs132793) polymorphism and Ligase IV, A6008G (Ile591Val) (rs2232641) polymorphism in breast cancer women were investigated. The genetic polymorphism analysis was performed using a DNA ABI PRISM 377 sequence detection system (Applied Biosystems) in 135 sporadic breast cancer cases. RESULTS: The distribution of the genotypes of the A46922G polymorphism of Ku70 in patients differed significantly (p < 0.05) from those predicted by the Hardy-Weinberg equilibrium. There were significant differences in the frequencies of alleles between the breast cancer subjects and controls (p < 0.05). However, the distribution of the genotypes of the A6008G polymorphism of Ligase IV in both controls and patients did not differ significantly (p > 0.05) from that predicted by the Hardy-Weinberg distribution. CONCLUSION: The results support the hypothesis that the A46922G polymorphism of the Ku70 gene may be associated with the incidence of breast cancer in women from the Lodz region of Poland.

Genetics polymorphism in DNA repair genes by base excision repair pathway (XRCC1) and homologous recombination (XRCC2 and RAD51) and the risk of breast carcinoma in the Polish population.

Background : Several polymorphisms in the DNA repair gene have been extensively studied in the association with various human cancers such as breast cancer. Material and methods : We investigated the association of polymorphisms in the DNA repair genes XRCC1-Arg399Gln, XRCC2-Arg188His and RAD51-135G/C with the breast cancer risk. Genotypes were determined by PCR-RFLP assays in 220 patients with breast cancer and 220 age-matched healthy controls. Results : Our results demonstrated a significant positive association between the XRCC1 399Gln/Gln homozygous genotype and breast carcinoma, with an adjusted odds ratio (OR) of 2.08 [1.08-3.98]. The 399Gln allele variant was also associated with type I breast cancer (OR = 1.41 [0.98-2.01], p = 0.034). The distributions of genotypes and alleles of the genes XRCC2 and RAD51 polymorphism were not significantly associated with the different stages of breast carcinoma (p > 0.05). Conclusion : These results suggest that 399Gln allele of XRCC1 Arg399Gln may be a risk factor for breast cancer in the Polish population.

XRCC1 and XRCC3 DNA repair gene polymorphisms in breast cancer women from the Lodz region of Poland.

AIM: Genetic polymorphism in XRCC1 and XRCC3 genes may influence DNA repair capacity and, in turn, confer predisposition to breast cancer. MATERIAL AND METHODS: In the present work the distribution of genotypes and frequency of alleles of the Arg194Trp and Arg399Gln polymorphism of XRCC1 and Trp241 Met polymorphism in XRCC3 in breast cancer women were analysed. Blood samples were obtained from 150 women with breast cancer and controls (n = 106). The polymorphisms were determined by PCR-RFLP methods. RESULTS: No association between XRCC1 Arg399Gln and Arg194Trp genotype and breast cancer risk was observed. The distribution of the genotypes of the Trp241 Met polymorphism of XRCC3 in both controls and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p > 0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. CONCLUSION: The results suggest that the Arg194Trp and Arg399Gln polymorphism of the XRCC1 gene as well as Trp241 Met polymorphism in XRCC3 may not be linked with appearance and development of breast cancer.