Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families.
We sequenced approximately 23 kb genomic regions containing all the coding exons and their franking introns of two breast cancer susceptibility genes, BRCA1 and BRCA2, of 55 individuals from 50 unrelated Japanese breast cancer families. We identified 55 single-nucleotide polymorphisms (SNPs) (21 in BRCA1 and 34 in BRCA2) containing nine pathogenic protein-truncating mutations (four in BRCA1 and five in BRCA2 from ten patients). Among the remaining 46 SNPs, allele frequencies of 40 were examined in both the breast cancer patients and 28 healthy volunteers with no breast cancer family history by PCR-RFLP or by direct DNA sequencing. Twenty-eight SNPs were common and were also found in the healthy volunteers and/or a SNP database. The remaining 18 were rare (allele frequency <0.05) and were not found in the healthy volunteers and/or the database. The pathogenic significance of these coding SNPs (cSNPs) remains to be clarified. The SNP information from this study will be useful in the future genetic testing of both BRCA1 and BRCA2 genes in the Japanese population.
Kawahara
Masanori
M
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.|Department of Second Surgery, Fukushima Prefecture College School of Medicine, Fukushima, Japan.
Sakayori
Masato
M
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Shiraishi
Kazuko
K
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.|Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Nomizu
Tadashi
T
Department of Surgery, Hoshi General Hospital, Koriyama, Japan.
Takeda
Motohiro
M
Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Abe
Rikiya
R
Tohoku Familial Tumor Association, Koriyama, Japan.
Ohuchi
Noriaki
N
Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Takenoshita
Seiichi
S
Department of Second Surgery, Fukushima Prefecture College School of Medicine, Fukushima, Japan.
Ishioka
Chikashi
C
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. chikashi@idac.tohoku.ac.jp.
D000483:Alleles; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D019992:Databases as Topic; D005091:Exons; D005192:Family Health; D005787:Gene Frequency; D019398:Genes, BRCA1; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D007564:Japan; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D024682:BRCA2 Protein