Linkage analysis and loss of heterozygosity for chromosome arm Ip in familial breast cancer

We conducted linkage analysis of 64 multiple-case families with early-onset bilateral breast cancer using DNA markers on chromosome band 1p36. Evidenc e against tight linkage was obtained using a dominant model for transmissio n (summary LOD scores at recombination fraction theta = 0.000001 were -4.71 for DIS160 and -2.70 for DIS170). Similar results were obtained after excl uding 20 families that were potentially attributable to BRCA1 or BRCA2. We also investigated loss of heterozygosity for a panel of markers on chromoso me arm 1p using breast tumors from affected family members. The most common regions of allele loss were 1p36 (32% for D1S160, 35% for D1S243) and 1p32 (51% for MYCL). The frequency and location of 1p allele loss did not diffe r substantially from previous studies of sporadic breast cancer. We conclud e that 1p36 probably does not contain a locus of susceptibility for a large proportion of breast cancer families, but a variety of loci on 1p may cont ribute to progression of familial and sporadic disease. Genes Chromosomes C ancer 25:354-361, 1999. (C) 1999 Wiley-Liss, Inc.