Abstract
Inherited predisposition occurs in 5–10% of all prostate cancer (CaP) patients, but the genes involved in conferring genetic susceptibility remain largely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Three mutations in these two genes (185delAG and 5382InsC (BRCA1) and 6174delT (BRCA2) occur in about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified restriction enzyme digests. Patient's age range was 45–81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55, and only one of them had a family history of breast and CaP. In addition, no allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the rate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not significantly differ from that of the general population, and that mutational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Abeliovich D, Kaduri L and Lerer I (1997) The founder mutation 185delAG and 5382insC in BRCA1 and 617delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer among Ashkenazi women. Am J Hum Genet 60: 505–514
Anderson DE and Badzioch MD (1993) Familial effects of prostate and other cancers on lifetime breast cancer risk. Breast Cancer Res Treat 28: 107–113
Arason A, Barkadottier RB and Egilsson V (1993) Linkage analysis of chromosome 17 markers and breast ovarian cancer in Icelandic families, and possible relationship to prostatic cancer. Am J Hum Genet 52: 711–717
Bar-Sade RB, Kruglikova A and Modan B (1998) The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim. Hum Mol Genet 7: 801–805
Briana JW, Emma J and Xiao LZ (1996) Evidence for a tumor suppressor gene distal to BRCA1 in prostate cancer. J Urol 155: 720–725
Carter BS, Beatty TH, Steinberg GD, Childs B and Walsh PC (1992) Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA 89: 3367–3371
Deubler DA, Williams BJ, Zhu XL, Steele MR, Rohr LR, Jensen JC, Stephenson RA, Changus JE, Miller GJ, Becich MJ and Brothman AR (1997) Allelic loss detected on chromosomes 8, 10 and 17 by fluorescence in situ hybridization using single-copy P1 probes on isolated nuclei from paraffin-embedded prostate tumors. Am J Pathol 150: 841–850
Easton DF, Ford D and Bishop DT the Breast Cancer Linkage Consortium (1995) Risks of cancer in BRCA1 mutation carriers. Am J Hum Genet 56: 265–271
Easton DF, Steele L and Fields P (1997) Cancer risks in two large breast cancer families linked to BRCA1 on chromosome 13q12–13. Am J Genet 61: 120–128
Ford D, Easton DF, Bishop DT, Narod SA and Goldgar DE (1994) The breast cancer linkage consortium. Risks of cancer in BRCA1 mutation carriers. Lancet 343: 692–695
Futreal PA, Cochran C and Rosenthal J (1994) Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture. Hum Mol Genet 3: 1359–1364
Gittes RF (1991) Carcinoma of the prostate. N Engl J Med 324: 236–245
Greer CE, Peterson SL, Kiviat NB and Manos MM (1991) PCR amplification from paraffin embedded tissues. Am J Clin Pathol 95: 117–124
Hubert A, Peretz T, Manor O, Kaduri L, Wienberg N, Lerer I, Sagi M and Abeliovich D (1999) The Jewish Ashkenazi founder mutations in the BRCA1/BRCA2 genes are not found at an increased frequency in Ashkenazi patients with prostate cancer. Am J Hum Genet 65: 921–924
Issacs SD, Kiemeney LALM, Baffoe-Bonnie A, Beaty TH and Walsh PC (1995) Risk of cancer in relatives of prostate cancer probands. J Natl Cancer Inst 87: 991–996
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
Knudson AG (1971) Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 68: 820–823
Langston AA, Stabford JL, Wicklund KG, Thompson JD, Blazej RG and Ostrander EA (1996) Germ-line BRCA1 mutations in selected men with prostate cancer. Am J Hum Genet 58: 881–885
Lehrer S, Fodor F, Stock RG, Stone NN, Eng C, Song HK and McGovern M (1998) Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer. Br J Cancer 78: 771–773
Melamed J, Einhorn JM and Ittmann MM (1997) Allelic loss on chromosome 13q in human prostate carcinoma. Clin Cancer Res 3: 1867–1872
Schneider NR, Chaganti SR, German J and Chagnti RSK (1983) Familial predisposition to cancer and age at onset of disease in randomly selected cancer patients. Am J Hum Genet 35: 454–467
Sellers TA, Potter JD, Rich SS, Drinkard CR, Bostick RM, Kushi LH, Zheng W and Folsom AR (1994) Familial clustering of breast and prostate cancers and risk for postmenopausal breast cancer. J Natl Cancer Inst 86: 1860–1865
Sheldon DN, Williams M and Fraley EE (1980) Incidental carcinoma of the prostate: a review of the literature and critical reappraisal of classification. J Urol 124: 626–631
Sigurdsson K, Thorlacius S and Tomasson J (1997) BRCA1 mutation in Icelandic prostate cancer patients. J Mol Med 75: 758–761
Struewing JP, Hartge P and Wacholder S (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336: 1401–1408
Tulinius H, Egilsson V, Olafsdottir GH and Sigvaldason H (1992) Risk of prostate, ovarian and endometrial cancer among relatives of women with breast cancer. Br Med J 305: 855–857
Watanabe M, Shiraishi T, Muneyuki T, Nagai M, Fukutome K, Murata M, Kawamura J and Yatani R (1998) Allelic loss and microsatellite instability in prostate cancers in Japan. Oncology 55: 569–574
Whittemore AS, Wu AH, Kolonel AN, John EM, Gallagher RP, Howe GR, West DW, The CZ and Stamey T (1995) Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol 141: 732–740
Wilkens EP, Freije D, Xu J, Nusskern DR, Suzuki H, Isaacs SD, Wiley K, Bujnovsky P, Meyers DA, Walsh PC and Isaacs WB (1999) No evidence for a role of BRCA1 or BRCA2 mutations in Ashkenazi Jewish families with hereditary prostate cancer. Prostate 39: 280–284
Williams BJ, Jones E, Zhu XL, Steele MR, Stephenson RA, Rohr LR and Brothman AR (1996) Evidence for a tumor suppressor gene distal to BRCA1 in prostate cancer. J Urol 155: 720–725
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Vazina, A., Baniel, J., Yaacobi, Y. et al. The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel. Br J Cancer 83, 463–466 (2000). https://doi.org/10.1054/bjoc.2000.1249
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1249
This article is cited by
-
BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis
British Journal of Cancer (2022)
-
Germline BRCA mutation in male carriers—ripe for precision oncology?
Prostate Cancer and Prostatic Diseases (2018)
-
The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer
Familial Cancer (2016)
-
The role of BRCA1 and BRCA2 in prostate cancer
Asian Journal of Andrology (2012)
-
BRCA1 and BRCA2 families and the risk of skin cancer
Familial Cancer (2010)