Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS Jg. 111; H. 39; S. 14205
Hauptverfasser:	Gabai-Kapara, Efrat, Lahad, Amnon, Kaufman, Bella, Friedman, Eitan, Segev, Shlomo, Renbaum, Paul, Beeri, Rachel, Gal, Moran, Grinshpun-Cohen, Julia, Djemal, Karen, Mandell, Jessica B, Lee, Ming K, Beller, Uziel, Catane, Raphael, King, Mary-Claire, Levy-Lahad, Ephrat
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 30.09.2014
Schlagworte:	Adult Aged Aged, 80 and over Breast Neoplasms - epidemiology Breast Neoplasms - genetics Female Genes, BRCA1 Genes, BRCA2 Genetic Carrier Screening Genetic Predisposition to Disease Genetic Testing - methods Genetics, Population Humans Israel - epidemiology Jews - genetics Male Middle Aged Ovarian Neoplasms - epidemiology Ovarian Neoplasms - genetics Risk Factors genomics
ISSN:	1091-6490, 1091-6490
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Abstract	In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.
AbstractList	In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations. In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.
Author	Levy-Lahad, Ephrat Renbaum, Paul Beeri, Rachel Gabai-Kapara, Efrat Lahad, Amnon Friedman, Eitan Catane, Raphael Beller, Uziel Mandell, Jessica B King, Mary-Claire Grinshpun-Cohen, Julia Kaufman, Bella Segev, Shlomo Lee, Ming K Djemal, Karen Gal, Moran
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References_xml	– reference: 21146769 - Am J Prev Med. 2011 Jan;40(1):61-6 – reference: 23788249 - Genet Med. 2013 Jul;15(7):565-74 – reference: 11179017 - Am J Hum Genet. 2001 Mar;68(3):700-10 – reference: 14576434 - Science. 2003 Oct 24;302(5645):643-6 – reference: 8988179 - Nat Genet. 1997 Jan;15(1):103-5 – reference: 20008623 - J Clin Oncol. 2010 Jan 20;28(3):387-91 – reference: 20616022 - Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12629-33 – reference: 8841191 - Nat Genet. 1996 Oct;14(2):185-7 – reference: 19690506 - Genet Med. 2009 Sep;11(9):620-1 – reference: 9145676 - N Engl J Med. 1997 May 15;336(20):1401-8 – reference: 23841703 - N Engl J Med. 2013 Aug 29;369(9):869-75 – reference: 16418514 - J Natl Cancer Inst. 2006 Jan 18;98(2):116-22 – reference: 20494256 - Obstet Gynecol Clin North Am. 2010 Mar;37(1):37-46 – reference: 12189225 - J Natl Cancer Inst. 2002 Aug 21;94(16):1221-6 – reference: 20653694 - Clin Genet. 2010 Nov;78(5):411-7 – reference: 18073579 - Genet Med. 2007 Oct;9(10):665-74 – reference: 15994883 - J Med Genet. 2005 Jul;42(7):602-3 – reference: 20810374 - JAMA. 2010 Sep 1;304(9):967-75 – reference: 17574839 - Eur J Cancer. 2007 Jul;43(11):1713-7 – reference: 17416853 - J Clin Oncol. 2007 Apr 10;25(11):1329-33 – reference: 24830819 - PLoS One. 2014;9(5):e97408 – reference: 17579227 - JAMA. 2007 Jun 20;297(23):2587-95 – reference: 12798717 - Gynecol Oncol. 2003 Jun;89(3):494-8 – reference: 9497246 - Am J Hum Genet. 1998 Mar;62(3):676-89 – reference: 23974829 - Breast Cancer Res Treat. 2013 Aug;141(1):135-44 – reference: 22608383 - Am J Prev Med. 2012 Jun;42(6):639-45 – reference: 11896095 - J Clin Oncol. 2002 Mar 15;20(6):1480-90 – reference: 23628597 - J Natl Cancer Inst. 2013 Jun 5;105(11):812-22 – reference: 24366376 - Ann Intern Med. 2014 Feb 18;160(4):271-81 – reference: 12510043 - N Engl J Med. 2003 Jan 2;348(1):50-8 – reference: 22430266 - J Clin Oncol. 2012 Apr 20;30(12):1321-8 – reference: 12677558 - Am J Hum Genet. 2003 May;72(5):1117-30
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Snippet	In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer...
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SubjectTerms	Adult Aged Aged, 80 and over Breast Neoplasms - epidemiology Breast Neoplasms - genetics Female Genes, BRCA1 Genes, BRCA2 Genetic Carrier Screening Genetic Predisposition to Disease Genetic Testing - methods Genetics, Population Humans Israel - epidemiology Jews - genetics Male Middle Aged Ovarian Neoplasms - epidemiology Ovarian Neoplasms - genetics Risk Factors
Title	Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2
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