Abstract
A number of molecular epidemiological studies have been conducted the screening for BRCA1 and BRCA2 mutations in breast cancer patients with a positive family history of breast and/or ovarian cancer and reported many common mutations in BRCA1 and BRCA2 associated in breast cancer in different population and different ethnicity. However, it’s still lack of a systematic analysis on these mutations. To comprehensively evaluate the frequency and distribution of common BRCA1 and BRCA2 mutations which associated with breast cancer risk, we address this issue through system review and meta-analysis on 29 relevant published studies by conducting a literature search on PubMed and CNKI. 20 common founder germline mutations were identified from all 29 studies and 4 of BRCA1 (5382insC, 185delAG, 3819del5 and 4153delA) and 2 of BRCA2 (4075delGT, 5802del4) mutations were repeatedly reported twice or more in different articles, respectively. For the BRCA1, after conducting meta-analysis, we found that the overall frequency of 5382insC was 0.09 (95% CI 0.06–0.12), the frequency of 185delAG was 0.07 (95% CI 0.01–0.13), the frequency of 3819del5 was 0.02 (95% CI 0.01–0.04) and the frequency of 4153delA was 0.06 (95% CI 0.03–0.09). For the BRCA2, the overall frequency of 4075delGT was 0.02 (95% CI 0.00–0.03) and the frequency of 5802del4 was 0.07 (95% CI 0.04–0.11). This article provides a set of common mutations for BRCA1 and BRCA2 mutation carriers and the results may help to explore frequencies of BRCA1 and BRCA2 mutations in a given population and will be of significance both for diagnostic testing and for epidemiological studies.
Similar content being viewed by others
References
Miki Y et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71
Wooster R et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792. doi:10.1038/378789a0
Tavtigian SV et al (1996) The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 12:333–337. doi:10.1038/ng0396-333
Narod SA et al (1995) An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium. Am J Hum Genet 56(1):254–264
Ford D et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676–689
Neuhausen SL (1999) Ethnic differences in cancer risk resulting from genetic variation. Cancer 86:2575–2582
Rebbeck TR (1999) Inherited genetic predisposition in breast cancer. A population-based perspective. Cancer 86:2493–2501
Struewing JP et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408
Anglian Breast Cancer Study Group (2000) Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group. Br J Cancer 83:1301–1308. doi:10.1054/bjoc.2000.1407
Claus EB, Risch N, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48:232–242
Schubert EL et al (1997) BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2. Am J Hum Genet 60:1031–1040
Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56:265–271
Sergentanis TN, Economopoulos KP (2010) Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis comprising 9,911 cases and 11,171 controls. Mol Biol Rep. doi:10.1007/s11033-010-0639-4
Chen MB et al (2010) Association of a LSP1 gene rs3817198T>C polymorphism with breast cancer risk: evidence from 33,920 cases and 35,671 controls. Mol Biol Rep. doi:10.1007/s11033-010-0603-3
Mann GJ et al (2006) Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource. Breast Cancer Res 8:R12. doi:10.1186/bcr1377
McKean-Cowdin R et al (2005) BRCA1 variants in a family study of African-American and Latina women. Hum Genet 116:497–506. doi:10.1007/s00439-004-1240-5
Saxena S et al (2006) Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India. BMC Med Genet 7:75. doi:10.1186/1471-2350-7-75
Peto J et al (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91:943–949. doi:10.1093/jnci/91.11.943
Spitzer E et al (2000) Detection of BRCA1 and BRCA2 mutations in breast cancer families by a comprehensive two-stage screening procedure. Int J Cancer 85:474–481. doi:10.1002/(SICI)1097-0215(20000215)85:4<474:AID-IJC5>3.0.CO;2-4
van Der Looij M et al (2000) Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland. Hum Mutat 15:480–481. doi:10.1002/(SICI)1098-1004(200005)15:5<480:AID-HUMU13>3.0.CO;2-G
Grzybowska E et al (2000) High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancer. Hum Mutat 16:482–490. doi:10.1002/1098-1004(200012)16:6<482:AID-HUMU5>3.0.CO;2-O
Vaziri SA et al (2001) Frequency of BRCA1 and BRCA2 mutations in a clinic-based series of breast and ovarian cancer families. Hum Mutat 17:74. doi:10.1002/1098-1004(2001)17:1<74:AID-HUMU13>3.0.CO;2-I
Ikeda N et al (2001) Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer 91:83–88. doi:10.1002/1097-0215(20010101)91:1<83::AID-IJC1013>3.0.CO;2-5
Palmieri G et al (2002) BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling. Ann Oncol 13:1899–1907. doi:10.1093/annonc/mdf326
Basham VM et al (2002) BRCA1 and BRCA2 mutations in a population-based study of male breast cancer. Breast Cancer Res 4:R2. http://breast-cancer-research.com/content/4/1/R2
Tereschenko IV et al (2002) BRCA1 and BRCA2 mutations in Russian familial breast cancer. Hum Mutat 19:184. doi:10.1002/humu.9008
Meindl A (2002) Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Int J Cancer 97:472–480. doi:10.1002/ijc.1626
Patmasiriwat P et al (2002) Analysis of breast cancer susceptibility genes BRCA1 and BRCA2 in Thai familial and isolated early-onset breast and ovarian cancer. Hum Mutat 20:230. doi:10.1002/humu.9049
Janiszewska H et al (2003) Frequency of three BRCA1 gene founder mutations in breast/ovarian cancer families from the Pomerania-Kujawy region of Poland. Clin Genet 64:502–508. doi:10.1046/j.1399-0004.2003.00178.x
Stuppia L et al (2003) BRCA1 and BRCA2 mutations in breast/ovarian cancer patients from central Italy. Hum Mutat 22:178–179. doi:10.1002/humu.9164
Gorski B et al (2004) A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int J Cancer 110:683–686. doi:10.1002/ijc.20162
Pal T et al (2004) BRCA1 and BRCA2 mutations in a study of African American breast cancer patients. Cancer Epidemiol Biomarkers Prev 13:1794–1799. http://cebp.aacrjournals.org/content/13/11/1794
Hu Z et al (2004) [Analysis of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives]. Zhonghua Zhong Liu Za Zhi 26:657–659
Pietschmann A et al (2005) Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families. J Cancer Res Clin Oncol 131:552–558. doi:10.1007/s00432-005-0678-8
van der Hout AH et al (2006) A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. Hum Mutat 27:654–666. doi:10.1002/humu.20340
Song CG et al (2006) The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer. J Cancer Res Clin Oncol 132:617–626. doi:10.1007/s00432-006-0105-9
Ang P et al (2007) BRCA1 and BRCA2 mutations in an Asian clinic-based population detected using a comprehensive strategy. Cancer Epidemiol Biomarkers Prev 16:2276–2284. doi:10.1158/1055-9965.EPI-07-0403
Thomassen M et al (2008) BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer. Acta Oncol 47:772–777. doi:10.1080/02841860802004974
Ratajska M et al (2008) BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland. Oncol Rep 19:263–268
Besic N et al (2008) BRCA2 gene mutations in Slovenian male breast cancer patients. Genet Test 12:203–209. doi:10.1089/gte.2007.0071
Konstantopoulou I et al (2008) Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients. Breast Cancer Res Treat 107:431–441. doi:10.1007/s10549-007-9571-2
Miramar MD et al (2008) Genetic analysis of BRCA1 and BRCA2 in breast/ovarian cancer families from Aragon (Spain): two novel truncating mutations and a large genomic deletion in BRCA1. Breast Cancer Res Treat 112:353–358. doi:10.1007/s10549-007-9868-1
Neuhausen SL et al (2009) BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry: an open resource for collaborative research. Breast Cancer Res Treat 116:379–386. doi:10.1007/s10549-008-0153-8
Cao MZ et al (2009) Analysis of BRCA1 mutations among familial and/or breast cancer praecox patients in the east of Shandong in China. Prog Mod Biomed 9:1028–1030 (in Chinese)
Infante M et al (2010) BRCA1 5272–1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin. Clin Genet 77:60–69. doi:10.1111/j.1399-0004.2009.01272.x
Vaidyanathan K et al (2009) BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identification of four novel mutations and high-frequency occurrence of 185delAG mutation. J Biosci 34:415–422
Tamboom K et al (2010) BRCA1 mutations in women with familial or early-onset breast cancer and BRCA2 mutations in familial cancer in Estonia. Hered Cancer Clin Pract 8:4. doi:10.1186/1897-4287-8-4
Egger M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101
Shattuck-Eidens D et al (1995) A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. JAMA 273:535–541
Roa BB et al (1996) Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 14:185–187. doi:10.1038/ng1096-185
Hartge P et al (1999) The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. Am J Hum Genet 64:963–970
Fodor FH et al (1998) Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 63:45–51
Warner E et al (1999) Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 91:1241–1247. doi:10.1093/jnci/91.14.1241
Levy-Lahad E et al (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
Abeliovich D et al (1997) The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 60:505–514
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Additional information
Furu Wang and Qiaoqiao Fang contributed equally.
Rights and permissions
About this article
Cite this article
Wang, F., Fang, Q., Ge, Z. et al. Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review. Mol Biol Rep 39, 2109–2118 (2012). https://doi.org/10.1007/s11033-011-0958-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-011-0958-0