Linkage analysis of BRCA1 in Japanese breast cancer families.
We examined the involvement of BRCA1, which plays a major role in Western breast cancer families, in Japanese breast cancer families. Eleven families, in which at least three individuals within third degree relatives were affected by breast cancer, were collected. Five of them were early-onset breast cancer families, in which the average age at diagnosis was less than 45 years, and the other six were late-onset families. Ovarian cancer was observed in one patient in the early-onset families. Using seven polymorphic markers on chromosome 17q21, D17S250, ERBB2, THRA1, D17S579, D17S588, GIP and NME1, linkage to BRCA1 was analyzed. Linkage was not detected in any single family. Assuming homogeneity in an inherited component that confines the susceptibility to breast cancer in all families, we summed the LOD scores of all families. The cumulative LOD score obtained was -1.86 for D17S588 at theta = 0.001, indicating no linkage with BRCA1. Since the proportion of families linked to BRCA1 is larger in Western early-onset breast cancer families than in late-onset ones, we also summed the LOD scores of five early-onset families. However, again a negative LOD score was obtained. These results suggest that BRCA1 is not a major breast cancer susceptibility gene in Japanese familial breast cancer.
Inoue
R
R
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo.
Fukutomi
T
T
Ushijima
T
T
Matsumoto
Y
Y
Sugimura
T
T
Nagao
M
M
D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008126:Lod Score; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology; D010375:Pedigree; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*
D019313:BRCA1 Protein; D017931:DNA Primers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014157:Transcription Factors