+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A high proportion of founder BRCA1 mutations in Polish breast cancer families



A high proportion of founder BRCA1 mutations in Polish breast cancer families



International Journal of Cancer 110(5): 683-686



Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and account for the majority of mutations identified to date in Polish breast and breast-ovarian cancer families. It is not known, however, to what extent these 3 founder mutations account for all of the BRCA mutations distributed throughout the country. This question has important implications for health policy and the design of epidemiologic studies. To establish the relative contributions of founder and nonfounder BRCA mutations, we established the entire spectrum of BRCA1 and BRCA2 mutations in a large set of breast-ovarian cancer families with origins in all regions of Poland. We sequenced the entire coding regions of the BRCA1 and BRCA2 genes in 100 Polish families with 3 or more cases of breast cancer and in 100 families with cases of both breast and ovarian cancer. A mutation in BRCA1 or BRCA2 was detected in 66% of breast cancer families and in 63% of breast-ovarian cancer families. Of 129 mutations, 122 (94.6%) were in BRCA1 and 7 (5.4%) were in BRCA2. Of the 122 families with BRCA1 mutations, 119 (97.5%) had a recurrent mutation (i.e., one that was seen in at least 2 families). In particular, 111 families (91.0%) carried one of the 3 common founder mutations. The mutation spectrum was not different between families with and without ovarian cancer. These findings suggest that a rapid and inexpensive assay directed at identifying the 3 common founder mutations will have a sensitivity of 86% compared to a much more costly and labor-intensive full-sequence analysis of both genes. This rapid test will facilitate large-scale national epidemiologic and clinical studies of hereditary breast cancer, potentially including studies of chemoprevention. (C) 2004 Wiley-Liss, Inc.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011686505

Download citation: RISBibTeXText

PMID: 15146557

DOI: 10.1002/ijc.20162


Related references

High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Research and Treatment 103(2): 225-232, 2006

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. American Journal of Human Genetics 60(5): 1041-1049, 1997

Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. Journal of Medical Genetics 51(2): 98-107, 2014

Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. American Journal of Human Genetics 66(6): 1963-1968, 2000

Founder mutations of BRCA1 and BRCA2 in North American families of Polish origin that are affected with breast cancer. American Journal of Human Genetics 68(2): 546-546, 2001

High frequency of pathogenic non-founder germline mutations in BRCA1 and BRCA2 in families with breast and ovarian cancer in a founder population. Hereditary Cancer in Clinical Practice 16: 12-12, 2018

Fifty percent of Jewish high-risk breast and ovarian cancer families are not explained by the three known BRCA1 or BRCA2 founder mutations while a 07 percent combined BRCA1 founder mutation frequency is reported in a Jewish cohort. American Journal of Human Genetics 59(4 SUPPL ): A28, 1996

High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer. Familial Cancer 11(4): 623-628, 2013

Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. Journal of Medical Genetics 39(8): 611-614, 2002

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families. Journal of Human Genetics 43(1): 42-48, 1998

Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. Human Mutation 22(4): 301-312, 2003

A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene. Human Genetics 103(2): 154-161, 1998

High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancer. Human Mutation 16(6): 482-490, 2000

BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin. Clinical Genetics 77(1): 60-69, 2010

BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families. International Journal of Cancer 110(5): 677-682, 2004