Surgical Decision Making in the BRCA-Positive Population: Institutional Experience and Comparison with Recent Literature.

A retrospective study was performed to document the uptake and extent of surgical intervention in patients with a known mutation in the BRCA1/2 genes and associated outcomes. Data were collected retrospectively on BRCA-positive patients with and without cancer at the time of genetic testing. Our findings were compared to those published in the current literature. Of patients with cancer at testing, 61% chose bilateral mastectomies. Of patients without cancer, 54% chose risk-reducing surgery (RRS) including risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), or both. Time to surgery was significantly shorter to RRSO than to RRM. The literature suggests and our data support that acceptance of RRM in the BRCA-positive population has gradually increased over time. Consistently high rates of RRSO uptake and short intervals from time-of-testing to RRSO demonstrate that RRSO is still more acceptable to this population than RRM.

Complex haplotype structure of the human GNAS gene identifies a recombination hotspot centred on a single nucleotide polymorphism widely used in association studies.

The alpha subunit of the heterotrimeric G protein Gs (Gsalpha) is involved in numerous physiological processes and is a primary determinant of cellular responses to extracellular signals. Genetic variations in the Gsalpha gene may play an important role in complex diseases and drug responses. To characterize the genetic diversity in this locus, we resequenced exons and flanking introns of the gene in 44 genomic samples and analysed the haplotype structure of the gene in an additional 50 African-Americans and 50 Caucasians. Significant differences in allele frequency for nearly all the genotyped single nucleotide polymorphism (SNPs) were detected between the two ethnic groups. Linkage disequilibrium (LD) analysis of this locus revealed two haplotype blocks characterized by strong LD and reduced haplotype diversity, especially in Caucasians. Between the two blocks is a narrow (approximately 3 kb) recombination hotspot centred on exons 4 and 5, and a widely used genetic marker in association studies in this region (rs7121) was in linkage equilibrium with the rest of the gene. The haplotype structure of the GNAS locus warrants reevaluation of previous association studies that used marker rs7121 and affects choice of SNP markers to be used in future studies of this locus.