Abstract
To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population. © 2000 Cancer Research Campaign
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References
Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N and Peretz T (1997) The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT inBRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 60: 505–514
Berman DB, Costalas J, Schultz DC, Grana G, Daly M and Godwin AK (1996) A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals. Cancer Res 56: 3409–3414
Breast Cancer Information Core (1999). http://www.nhgri.nih.gov/Intramural_research/Lab_transfer/Bic/Member/index.html
Couch FJ and Weber BL (1996) Mutations and polymorphisms in the familial early-onset breast cancer BRCA1 gene. Breast cancer Information Core. Hum Mutat 8: 8–18
Couch FJ, DeShano ML, Blackwood MA, Calzone K, Stopfer J, Campeau L, Ganguly A, Rebbeck T and Weber BL (1997) BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 336: 1409–1415
Csokay B, Tihomirova L, Stengrevics A, Sinicka O and Olah E (1999) Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia. Hum Mutat 14: 92
Easton DF, Bishop DT, Ford D and Crockford GP The Breast Cancer Linkage Consortium (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet 52: 678–701
Ford D, Easton DF, Bishop DT, Narod SA and Goldgar DE Breast Cancer Linkage Consortium (1994) Risks of cancer in BRCA1-mutation carriers. Lancet 343: 692–695
Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonnin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Birch JM, Lindblom A, Stoppa-Lyonnet D, Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM, Vasen H, Seitz S, Cannon-Albright,, Schofield A and Zelada-Hedman M Breast Cancer Linkage Consortium (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62: 676–689
Friedman LS, Szabo CI, Ostermeyer EA, Dowd P, Butler L, Park T, Lee MK, Goode EL, Rowell SE and King MC (1995) Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. Am J Hum Genet 57: 1284–1297
Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF and Ponder BA (1997) Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia. Am J Hum Genet 60: 1239–1242
Hakansson S, Johannsson O, Johansson U, Sellberg G, Loman N, Gerdes AM, Holmberg E, Dahl N, Pandis N, Kristoffersson U, Olsson H and Borg A (1997) Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer. Am J Hum Genet 60: 1068–1078
Johannesdottir G, Gudmundsson J, Bergthorsson JT, Arason A, Agnarsson BA, Eiriksdottir G, Johannsson OT, Borg A, Ingvarsson S, Easton DF, Egilsson V and Barkardottir RB (1996) High prevalence of the 999del5 mutation in Icelandic breast and ovarian cancer patients. Cancer Res 56: 3663–3665
Langston AA, Malone KE, Thompson JD, Daling JR and Ostrander EA (1996) BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med 334: 137–142
Levy-Lahad E, Catane R, Eisenberg S, Kaufman B, Hornreich G, Lishinsky E, Shohat M, Weber BL, Beller U, Lahad A and Halle D (1997) Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. Am J Hum Genet 60: 1059–1067
Neuhausen S, Gilewski T, Norton L, Tran T, McGuire P, Swensen J, Hampel H, Borgen P, Brown K, Skolnick M, Shattuck-Eidens D, Jhanwar S, Goldgar D and Offit K (1996) Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nat Genet 13: 126–128
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavigain S, Liu Q, Cochran C, Bennet LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barret C, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A and Skolnick M (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266: 66–71
Ozcelik H, Antebi Y, Cole DEC and Andrulis IL (1996) Heteroduplex and protein truncation analysis of the BRCA1 185delAG mutation. Hum Genet 98: 310–312
Ozcelik H, Schmocker B, Di Nicola N, Shi XH, Langer B, Moore M, Taylor BR, Narod SA, Darlington G, Andrulis IL, Gallinger S and Redston M (1997) Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet 16: 17–18
Phelan CM, Lancaster JM, Tonin P, Gumbs C, Cochran C, Carter R, Ghadirian P, Perret C, Moslehi R, Dion F, Faucher MC, Dole K, Karimi S, Foulkes W, Lounis H, Warner E, Goss P, Anderson D, Larsson C, Narod SA and Futreal PA (1996) Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet 13: 120–122
Simard J, Tonin P, Durocher F, Morgan K, Rommens J, Gingras S, Samson C, Leblanc JF, Belanger C, Dion F, Liu Q, Skolnick M, Goldgar D, Shattuck-Eidens D, Labrie F and Narod SA (1994) Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet 8: 392–398
Southey MC, Tesoriero AA, Andersen CR, Jennings KM, Brown SM, Dite GS, Jenkins MA, Osborne RH, Maskiell JA, Porter L, Giles GG, McCredie MR, Hopper JL and Venter DJ (1999) BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer. Br J Cancer 79: 34–39
Szabo CI and King MC (1997) Population genetics of BRCA1 and BRCA2. Am J Hum Genet 60: 1013–1020
Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, Merajver S, Thorlacius S, Offit K, Stoppa-Lyonnet D, Belanger C, Bell R, Berry S, Bogden R, Chen Q, Davis T, Dumont M, Frye C, Hattier T, Jammulapati S, Janecki T, Jiang P, Kehrer R, Leblanc JF, Leblane JF, Mitchell JT, MeArthur-Morrison J, Nguyenk K, Peng Y, Sanson C, Schroeder M, Snyder SC, Steele L, Stringfellow M, Stroup C, Swedlund B, Swensen J, Teng D, Thomas A, Tran A, Tran T, Tranchant M, Weaver-Feldhaus J, Wong AKC, Shizuya H, Eyfjord JE, Cannon-Albright L, Labrie F, Skolnick MH, Weber B, Kamb A and Goldgar DE (1996) The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 12: 333–337
Tadmouri GO, Tuzmen S, Ozcelik H, Ozer A, Baig SM, Senga EB and Basak AN (1998) Molecular and population genetic analyses of beta-thalassemia in Turkey. Am J Hematol 57: 215–220
Turkish Ministry of Health (1994). Republic of Turkey Health Statistics, Turkish Ministry of Health( web page: www.saglik.gov.tr/turkce/istatistikler/s91_tur.htm)
Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G, Barfoot M, Hamoudi R, Patel S, Rice C, Biggs P, Hashim Y, Smith A, Connor F, Arason A, Gudmundsson J, Ficenec D, Keisell D, Ford D, Tonin P, Bishop DT, Spurr NK, Ponder BAJ, Eeles R, Pete J, Devilee P, Carnelisse C, Lynch H, Narod S, Lenoir G, Eglisson V, Bjork-Barkadottir R, Easton DF, Bentley DR, Futreau PA, AshWorth A and Stratton MR (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789–792
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Yazici, H., Bitisik, O., Akisik, E. et al. BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients. Br J Cancer 83, 737–742 (2000). https://doi.org/10.1054/bjoc.2000.1332
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DOI: https://doi.org/10.1054/bjoc.2000.1332
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