XRCC1 gene polymorphisms in a population sample and in women with a family history of breast cancer from Rio de Janeiro (Brazil)

Abstract

The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility.

TP53 and XRCC1 polymorphisms and breast cancer prognosis: a case-case study

“…The histological grading system proposed by Scarff-Bloom-Richardson and modified by Elston and Ellis in 199133 is an important independent prognostic factor for invasive breast tumors. The two groups of patients in our study were rather homogenous in terms of age and ethnicity and our genotyping results for XRCC1 variants Arg194Trp and Arg399Gln showed the distribution expected in a Brazilian population 23-26. Together these observations indicate that our group of patients is adequate for a case-case study.…”

“…The two groups of patients in our study were rather homogenous in terms of age and ethnicity and our genotyping results for XRCC1 variants Arg194Trp and Arg399Gln showed the distribution expected in a Brazilian population. 23 - 26 Together these observations indicate that our group of patients is adequate for a case-case study. Our study revealed a statistically significant relationship between the Arg194Trp genotype of XRCC1 and Elston grade III, which indicates a poorly differentiated tumor and, consequently, is related to increased aggressiveness of the disease.…”

“…None of the analyzed characteristics, including age, menopausal status, family history, or ethnicity, were differentially distributed between the patients with EG I/II (low/intermediate aggressiveness) and EG III (high aggressiveness). The allelic frequencies of the TP53 polymorphisms PIN3 Ins16bp and Arg72Pro of 0.2 and 0.4, respectively, and of the XRCC1 polymorphisms Arg194Trp and Arg399Gln of 0.07 and 0.25, respectively, were in accordance with Hardy-Weinberg equilibrium 20-26. Then we proceeded with the association analysis between tumor pathological characteristics and the allelic distribution of the variants (Table 3).…”

“…The allelic frequencies of the TP53 polymorphisms PIN3 Ins16bp and Arg72Pro of 0.2 and 0.4, respectively, and of the XRCC1 polymorphisms Arg194Trp and Arg399Gln of 0.07 and 0.25, respectively, were in accordance with Hardy-Weinberg equilibrium. 20 - 26 Then we proceeded with the association analysis between tumor pathological characteristics and the allelic distribution of the variants ( Table 3 ). We found a statistically positive association with the 194Trp XRCC1 allele and EG III (OR = 4.04; 95% CI = 1.30-12.35; p = 0.018).…”

Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients

“…DNA damage plays a central role in carcinogenesis. Consequently, genes involved in DNA repair are considered key genes in cancer development (1).…”