About 5-10 % of breast cancer is due to inherited disease predisposition. Currently known susceptibility genes such as BRCA1 and BRCA2 explain less than 25 % of familial aggregation of breast cancer, which suggests the involvement of additional genetic susceptibility. The SHFM1 [split hand/foot malformation (ectrodactyly) type 1] gene plays an important role in the regulation of gene transcription and cell proliferation and may be involved in the maintenance of genomic integrity. It is a potential candidate for being involved in heritable cancer susceptibility due to its biological function. The SHFM1 protein binds in mammalian cells to the longest conserved region of the BRCA2 protein and is required for BRCA2 stability and function, making a critical contribution to the BRCA2 function in mediating homologous recombination. Therefore, variants in the SHFM1 gene could affect the BRCA2 functionality and be associated with the familial breast/ovarian carcinogenesis.
We have screened the entire coding region and splice junctions of SHFM1 in affected index cases from 369 Spanish breast/ovarian cancer families for germ line defects, using direct sequencing.
Mutation analysis revealed seven different sequence changes. Based on the in silico analyses of these sequence alterations, as well as their occurrence in cases and controls, none of them, however, were predicted to be pathogenic or associated with cancer susceptibility.
To our knowledge, this is the most comprehensive study reporting the mutation screening of the SHFM1 gene in familial breast/ovarian cancer cases. No evidence for the association with breast/ovarian cancer was observed.
"To investigate the possible role of ERCC4 in breast and ovarian cancer susceptibility, we screened, by DHPLC (denaturing highperformance liquid chromatography) and direct sequencing, the 11 coding exons and exon–intron boundaries of the ERCC4 gene in 1573 index cases from high-risk Spanish familial breast and ovarian cancer pedigrees that had been tested negative for mutations in BRCA1 and BRCA2 and 854 controls without personal or familial antecedents of cancer. Criteria for inclusion of cases and controls, and methods of screening for mutations in BRCA1/2 have been previously published [Bonache et al., 2013; Fernandez- Rodriguez et al., 2012; Osorio et al., 2012; Romero et al., 2011] "
[Show abstract][Hide abstract] ABSTRACT: Recently, it has been reported that biallelic mutations in the ERCC4 (FANCQ) gene cause Fanconi anemia (FA) subtype FA-Q. To investigate the possible role of ERCC4 in breast and ovarian cancer susceptibility, as occurs with other FA genes, we screened the 11 coding exons and exon-intron boundaries of ERCC4 in 1573 index cases from high-risk Spanish familial breast and ovarian cancer pedigrees that had been tested negative for BRCA1 and BRCA2 mutations and 854 controls. The frequency of ERCC4 mutation carriers does not differ between cases and controls, suggesting that ERCC4 is not a cancer susceptibility gene. Interestingly, the prevalence of ERCC4 mutation carriers (one in 288) is similar to that reported for FANCA, whereas there are approximately 100-fold more FA-A than FA-Q patients, indicating that most biallelic combinations of ERCC4 mutations are embryo lethal. Finally, we identified additional bone-fide FA ERCC4 mutations specifically disrupting interstrand cross-link repair. This article is protected by copyright. All rights reserved.
Human Mutation 12/2013; 34(12). DOI:10.1002/humu.22438 · 5.14 Impact Factor
"Approximately 25% of breast cancers are inherited by germ-line mutations in functional and/or oncogenes (Akbari et al., 2013; Carraro et al., 2013; Sohail et al., 2013). As claimed by Bonache et al there are various involvement of additional genetic susceptibility in BC (Bonache et al., 2013). Population based mutation type was reported in BRCA genes in BC (Akbari et al., 2013). "
[Show abstract][Hide abstract] ABSTRACT: Background:
Various oncogenes related to cancer have been extensively studied and several polymorphisms have been found to be associated with breast cancer. The current report outlines analysis of germ-line polymorphisms for C677T, A1298C (MTHFR), Leiden, R2 (FV) and 5G/4G (PAI-1) in Turkish breast cancer patients. We studied 51 cases diagnosed with invasive ductal and operable with lymph node-positive breast cancer and 106 women as a control group.
Materials and methods:
Peripheric blood-DNA samples were used for genotyping by StripAssay technique which is based on the reverse-hybridization principle and real-time PCR methods and results were compared statistically.
The frequency of the MTHFR gene 677T and 1298A alleles were significantly higher in cancer patients than in the healthy subjects. The T allele frequency in codon 677 was 2.3-fold and C allele frequency was 3.1-fold increased in BC when compared to the control group for the MTHFR gene. Both differences were statistically significant (OR: 2.295, CI: 1.283-4.106), p<0.006 and (OR: 3.131, CI:1.826-5.369), p<0.0001 respectively. The R2 allele frequency of FV gene was 5.1-fold increased in the current BC when compared to the control group and that difference was also statistically significant (OR: 5.133, CI: 1.299-20.28), p<0.02.
The present data suggest that germ-line polymorphisms of C677T, C1298A for MTHFR and R2 for FV are associated in breast cancer and may be additional prognostic markers related to breast cancer survival. The results now need to be confirmed in a larger group of patients.
Asian Pacific journal of cancer prevention: APJCP 05/2013; 14(5):2903-2908. DOI:10.7314/APJCP.2013.14.5.2903 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: About 5-10% of breast cancer is due to inherited disease predisposition. Currently mutations in the BRCA1 and BRCA2 genes explain less than 25% of the familial clustering of breast cancer and additional susceptibility genes are suspected. The BCCIP gene plays an important role in the regulation of gene transcription and cell proliferation and could be involved in the maintenance of genomic integrity. The BCCIP protein binds in mammalian cells to the longest conserved region of the BRCA2 protein and is required for BRCA2 stability and function, making a critical contribution to the function of BRCA2 in mediating homologous recombination. Variants in the BCCIP gene could affect the BRCA2 functionality and be associated to the familial breast/ovarian carcinogenesis. Therefore, BCCIP gene is a potential candidate for being involved in heritable cancer susceptibility.
We have screened the entire coding region and splice junctions of BCCIP in affected index cases from 215 Spanish breast/ovarian cancer families for germ line defects, using direct sequencing.
Mutation analysis revealed 3 different intronic sequence changes. Conclusions Based on the in silico and in vitro RNA analyses of these sequence alterations, none of them were predicted to be pathogenic or associated with cancer susceptibility. Our results indicate that BCCIP germ line mutations are unlikely to be a major contributor to familial breast/ovarian cancer risk in our population.
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