Prevalence and clinical correlations of BRCA1/BRCA2 unclassified variant carriers among unselected primary ovarian cancer cases – preliminary report

Majdak, E.; Bock, Geertruida H. de; Brożek, Izabela; Perkowska, Magdalena; Ochman, Karolina; Dȩbniak, Jarosław; Milczek, Tomasz; Cornelisse, Cees J.; Jassem, Jacek; Emerich, Janusz; Limon, Janusz; Devilee, Peter

doi:10.1016/j.ejca.2004.10.011

Cited by 21 publications

(15 citation statements)

References 34 publications

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“…Concomitantly, the prevalence of missense substitutions: Leu871Pro, GLu1038Gly, Ser1613Gly, Gly1140Ser in BRCA1 gene of many patients aged 30-35 years and compared with results of controls shows that haplotype at the BRCA1 locus probability defined by these alleles (Leu871Pro,GLu1038Gly, Ser1613Gly,Gly1140Ser) may have an pathogenic effect, but haplotypes of BRCA1 defined by single alleles of Glu1038Gly, Ser1613Gly, Gly1140ser and Glu1038Gly, Gly1140Ser in carriers are associated with low-penetrance predisposition to breast or ovarian cancer. Dunning reported similar results in his studies [31]. The three BRCA1 variants of uncertain significance identified in this study correspond to substitutions in exons 2, 6, 11 and 13 ( Table 3) and none of them, are likely to be clinically relevant.…”

Section: Discussionsupporting

confidence: 83%

“…In previous studies associations have been shown between these two alleles with missense substitutions GLu1038Gly [30]. In 2005, the polymorphism Ser1613Gly was introduced as a mutation predisposing to ovarian cancer by Majdak [31]. Concomitantly, the prevalence of missense substitutions: Leu871Pro, GLu1038Gly, Ser1613Gly, Gly1140Ser in BRCA1 gene of many patients aged 30-35 years and compared with results of controls shows that haplotype at the BRCA1 locus probability defined by these alleles (Leu871Pro,GLu1038Gly, Ser1613Gly,Gly1140Ser) may have an pathogenic effect, but haplotypes of BRCA1 defined by single alleles of Glu1038Gly, Ser1613Gly, Gly1140ser and Glu1038Gly, Gly1140Ser in carriers are associated with low-penetrance predisposition to breast or ovarian cancer.…”

Section: Discussionmentioning

confidence: 98%

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BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients

2011

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Breast cancer is the most common cancer in Iranian women (Mousavi et al in Asian Pac J Cancer Prev 9(2):275-278, 2008). Genetic predisposition accounts for 15% of all breast cancers and germline mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 are responsible for a substantial proportion of high-risk breast and breast/ovarian cancer families (Collaborative Group on Hormonal Factors in Breast Cancer in Lancet 350:1047-1059, 1997; Lee et al in Int Nurs Rev 55:355-359, 2008; Hulka and Stark in Lancet 346:883-887, 1995; Kelsey in Epidemiol Rev 15:256-263, 1993; Tischer et al in J Biol Chem 266:11947-11954, 1991; Newman et al in: Proc Natl Acad Sci USA 85:3044-3048, 1988). Therefore, the aim of this study was to investigate mutations of BRCA1/2 in high risk Iranian families. We screened 85 patients who met our minimal criteria. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened by direct sequencing. In the present study, we could detect the novel following mutations: p.Glu1735 p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Arg7Cys, p.Ser177Thr, IVS7+83(TT), IVS8-70(-CATT), IVS2+9(-GC), IVS1-20(-GA), IVS1-8(-AG), IVS2+24(AG), IVS5-8 (A-G), IVS2(35-39)TTcctatGAT in BRCA1 and p.Glu1391Gly, 1994_1995 (Ins A), IVS6-70-T>G in BRCA2. In agreement with findings in other populations, we found that family history is a good predictor of being a mutation carrier. Five pathogenic BRCA1 mutations and one pathogenic BRCA2 mutation were detected in 85 index cases.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 98%

BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients

2011

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“…The lifetime risk of developing ovarian cancer in BRCA1 and BRCA2 carriers is 28-44% [1,2,6,7]. Estimates of the frequency of BRCA1 and BRCA2 germline mutations in ovarian cancer patients have ranged between 2-12% and 2-6% for BRCA1 and BRCA2 mutations, respectively [2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Improved survival in BRCA2 carriers with ovarian cancer

et al. 2006

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Objectives-The objective of this study was to investigate survival of ovarian cancer patients with BRCA1 and BRCA2 mutations compared to those without mutations in a population-based sample of incident epithelial ovarian cancer cases. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript the two analyses were similar, thus data involving the 209 invasive epithelial cancer cases are presented, as this was judged to be more clinically relevant. NIH Public AccessResults-In the multivariate analysis, BRCA status and stage were statistically significant, and were adjusted for in the survival analysis model. The Kaplan-Meier method estimated expected survival at 4 years of 83% of BRCA2 carriers compared to 37% of BRCA1 carriers and 12% of non-carriers. There was a statistically significant difference between BRCA2 carriers and noncarriers (p = 0.013). No statistically significant survival differences were seen for BRCA1 carriers when compared with either BRCA2 carriers or non-carriers.Conclusion-These data suggest that BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and non-carriers. The etiology of this possible survival advantage is currently unknown. Larger studies are needed to confirm these results and to clarify their etiology and clinical significance.

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“…the frequency of these mutations in ovarian cancer range between 2-12% for BRCA1 and 2-6% for BRCA2 mutations (Risch et al 2001;Majdak et al 2005). BRCA1/2 act as tumor suppressors and play a role in maintaining genomic stability through DNA damage recognition and repair, transcriptional regulation, and cell cycle control (Scully and Livingston 2000).…”

Section: Discussionmentioning

confidence: 99%