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A high proportion of founder BRCA1 mutations in Polish breast cancer families
Author(s) -
Górski Bohdan,
Jakubowska Anna,
Huzarski Tomasz,
Byrski Tomasz,
Gronwald Jacek,
Grzybowska Ewa,
Mackiewicz Andrzej,
Stawicka Malgorzata,
Bębenek Marek,
Sorokin Dagmara,
FiszerMaliszewska Łucja,
Haus Olga,
Janiszewska Hanna,
Niepsuj Stanisław,
Góźdź Stanisław,
Zaremba Lech,
Posmyk Michał,
Płużańska Maria,
Kilar Ewa,
Czudowska Dorota,
Waśko Bernard,
Miturski Roman,
Kowalczyk Jerzy R.,
Urbański Krzysztof,
Szwiec Marek,
Koc Jan,
Dębniak Bogusław,
Rozmiarek Andrzej,
Dębniak Tadeusz,
Cybulski Cezary,
Kowalska Elzbieta,
TołoczkoGrabarek Aleksandra,
Zajączek Stanisław,
Menkiszak Janusz,
Mędrek Krzysztof,
Masojć Bartłomiej,
Mierzejewski Marek,
Narod Steven Alexander,
Lubiński Jan
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20162
Subject(s) - ovarian cancer , breast cancer , founder effect , mutation , brca2 protein , cancer , genetics , brca mutation , biology , gene , medicine , oncology , germline mutation , haplotype , genotype
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. © 2004 Wiley‐Liss, Inc.