The investigation of DNA repair polymorphisms with histopathological characteristics and hormone receptors in a group of Brazilian women with breast cancer

Abstract

ABSTRACT. The association of tumor differentiation and estrogen receptor expression with the prognosis of breast cancer has been well established. Nevertheless, little is yet reported about the association of morphological characteristics of the tumor, estrogen receptor status and polymorphisms in low penetrance genes. The aim of the present study was to investigate a possible association between DNA repair gene polymorphisms (XRCC1, XPD, XRCC3, and RAD51) with histological type, grade and hormone receptor expression in a series of breast cancers. A cross-sectional study was carried out to evaluate 94 women with breast carcinoma, who had already 575 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 7 (3): 574-582 (2008) DNA repair polymorphisms and breast cancer risk been selected and included in a study on the association of DNA repair gene polymorphisms. For immunohistochemistry, formalinfixed, paraffin-embedded tissue samples from breast tumors were consecutively retrieved from the histopathology files of our institution. DNA obtained from blood samples of the same patients was investigated for the presence of the following polymorphisms: Arg399Gln located in the XRCC1 gene; 135C/G located in the RAD51 gene; Lys751Gln located in the XPD gene and Thr241Met located in the XRCC3 gene. Polymorphisms were considered to be independent variables and hormone receptor expression and the morphological characteristics of the tumors comprised the dependent variables. No statistically significant association was found between gene polymorphisms and hormone receptor status. The association between XRCC1-Arg399Gln polymorphism and ductal carcinoma was statistically significant (P = 0.02). The association of the XPDLys751Gln polymorphism with histological grade was also statistically significant (P = 0.05). In conclusion, the XRCC1 genotype was found to be associated with ductal carcinoma histotypes and XPD genotype with low histological grade, which is the most frequent pattern of sporadic breast carcinomas.

Association between the XRCC3 Thr241Met Polymorphism and Breast Cancer Risk: an Updated Meta-analysis of 36 Case-control Studies

“…Out of the 100 abstracts retrieved through the search criteria, fifty-four were irrelevant, nine articles were excluded because they were conducted on other XRCC3 polymorphisms. Four studies (Bewick et al, 2006;Popanda et al, 2006;Dufloth et al, 2008;Falvo et al, 2011)was excluded given that it has not included controls , seven articles were reviews or meta-analyses. As a result, 26 case-control articles involving 36 studies were included in this meta-analysis.…”

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

“…Similar to this even European population didn't show any association with XRCC1 399 polymorphism in lung cancer patients (Lopez-Cima et al, 2007) and in bladder patients (Kelsey et al, 2004). Some studies have also demonstrated a strong association of the Arg399Gln XRCC1 polymorphism with an increased risk of breast cancer (Chacko, 2005;Dufloth et al, 2008;Sterpone et al, 2010). However in 2006, the Breast Cancer Association Consortium, as well as a large meta-analysis, reported no evidence of its association with breast cancer development (Breast Cancer Association Consortium, 2010).…”

Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer

“…Additional studies were manually searched in the reference list of all studies identified. Eligible studies had genotypic data with a casecontrol design and duplicates of previous studies were excluded [16]. As a result, we have identified a total of 33 eligible articles, which investigated the association of one or both polymorphisms, Asp312Asn and Lys751Gln, with breast cancer risk where 29 studied a single ethnic population.…”