Article

Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility

Department of Medical Oncology, University Hospital, Groningen, The Netherlands.
Journal of Medical Genetics (Impact Factor: 5.64). 05/2002; 39(4):225-42.
Source: PubMed

ABSTRACT This review focuses on genes other than the high penetrance genes BRCA1 and BRCA2 that are involved in breast cancer susceptibility. The goal of this review is the discovery of polymorphisms that are either associated with breast cancer or that are in strong linkage disequilibrium with breast cancer causing variants. An association with breast cancer at a 5% significance level was found for 13 polymorphisms in 10 genes described in more than one breast cancer study. Our data will help focus on the further analysis of genetic polymorphisms in populations of appropriate size, and especially on the combinations of such polymorphisms. This will facilitate determination of population attributable risks, understanding of gene-gene interactions, and improving estimates of genetic cancer risks.

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    • "Inherited mutations in the breast cancer susceptibility gene 1 (BRCA1) [MIM 113705] and breast cancer susceptibility gene 2 (BRCA2) [MIM 600185] are associated with a high risk of developing breast and ovarian cancers in females of different age and ethnic groups. These well-defined high-penetrance genes show loss-of-full function germ line mutations in hereditary cases and decreased expression in sporadic tumors [2] [3] [4]. Approximately, 5 to 10 percent of breast cancer [5] and at least 10 percent of ovarian cancers [6] are hereditary. "
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    ABSTRACT: Introduction. Pakistani population has a very rich anthrogeneological background with waves of migration from neighboring regions. Incidence rates of breast and ovarian cancer in Pakistan are on such a rapid rise that it is necessary to check the contributory factors, genetic and nongenetic. An insight into the prevalence data emphasizes the formulation of a BRCA1 and BRCA2 database for the Pakistani population. Method. In this study conducted by authors, data from diagnosed cases of both sporadic and inherited female breast and ovarian cancer cases was gathered after performing molecular genetic analysis by screening for alterations in the coding sequence of the BRCA gene. The region of interest was analyzed by the aid of various molecular biology tools such as automated DNA sequencer. Bioinformatics software was used to interpret the results, and database was prepared. Results. Mutational screening of the exons in all the samples of our study group did not reveal any pathogenic mutation. These results along with the results of the previous Pakistani studies for both BRCA1 and BRCA2 genes were summed up to prepare a Pakistani database. Percentage involvement of these genes was estimated. Nine percent of these cancers show alterations in BRCA1 gene while 3 percent have shown BRCA2 variants. The remaining 88 percent of breast and ovarian cancers can be attributed to the involvement of other genes.
    Journal of Oncology 03/2011; 2011:632870. DOI:10.1155/2011/632870
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    • "Nevertheless, the sample size had insufficient statistical power to provide conclusive answers with respect to the association between these gene polymorphisms and negative ER expression. Gene polymorphisms that are part of the steroid hormone pathways may alter the levels and/or effects of endogenous hormones , and therefore influence breast cancer risk (de Jong et al., 2002). Taken together, a number of studies have evaluated the association of polymorphisms in low-penetrance genes such as XRCC3, PR, ER, XRCC1, and BRCA2 with increased or decreased breast cancer risk (Smith et al., 2003; Dufloth et al., 2005; Lakhani et al., 2005; Costa et al., 2007, 2008). "
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    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 been selected and included in a study on the association of DNA repair gene polymorphisms. For immunohistochemistry, formalin-fixed, 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: Arg-399Gln 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 XPD-Lys751Gln polymorphism with histological grade was also tatistically 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.
    Genetics and molecular research: GMR 02/2008; 7(3):574-82. DOI:10.4238/vol7-3gmr376 · 0.85 Impact Factor
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    • "Patients with Petz–Jeghers syndrome have been found to be at increased risk of breast cancer (Boardman et al., 1998). This syndrome is caused by truncating mutations in the LKB1 gene, but its involvement in breast cancer appears to be only in patients with the syndrome (Hemminki et al., 1998; Jenne et al., 1998; de Jong et al., 2002). "
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    ABSTRACT: One of the most important risk factors for breast cancer is family history of the disease, indicating that genetic factors are important determinants of breast cancer risk. A number of breast cancer susceptibility genes have been identified, the most important being BRCA1 and BRCA2. However, it is estimated that all the currently known breast cancer susceptibility genes accounts for less than 25% of the familial aggregation of breast cancer. In this paper, we review the evidence for other breast cancer susceptibility genes arising from twin studies, pedigree analysis and studies of phenotypes associated with breast cancer, and the progress towards finding other breast cancer susceptibility genes through linkage and association studies. Taken together, the available evidence indicates that susceptibility to breast cancer is mediated through variants in many genes, each conferring a moderate risk of the disease. Such a model of susceptibility has implications for both risk prediction and for future gene identification studies.
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