title: Variants in the Signaling Protein TSAd are Associated with Susceptibility to Ovarian Cancer in BRCA1/2 Negative High Risk Families.
abstract: A substantial fraction of familial ovarian cancer cases cannot be attributed to specific genetic factors. The discovery of additional susceptibility genes will permit a more accurate assessment of hereditary cancer risk and allow for monitoring of predisposed women in order to intervene at the earliest possible stage. We focused on a population with elevated familial breast and ovarian cancer risk. In this study, we identified a SNP rs926103 whose minor allele is associated with predisposition to ovarian but not breast cancer in a Caucasian high-risk population without BRCA1/BRCA2 mutations. We have found that the allelic variation of rs926103, which alters amino acid 52 of the encoded protein SH2D2A/TSAd, results in differences in the activity of this protein involved in multiple signal transduction pathways, including regulation of immune response, tumor vascularization, cell growth, and differentiation. Our observation provides a novel candidate genetic biomarker of elevated ovarian cancer risk in members of high-risk families without BRCA1/2 mutations, as well as a potential therapeutic target, TSAd.
authors.affiliation: Program in Molecular Imaging and Biomarkers, Wayne State University School of Medicine, Detroit MI. ; Department of Oncology, Wayne State University School of Medicine, Detroit MI.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kaplun
authors.forename: Aviva Levine
authors.initials: AL
authors.lastname: Fridman
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Levin
authors.forename: Sidra
authors.initials: S
authors.lastname: Ahsan
authors.forename: Nancie
authors.initials: N
authors.lastname: Petrucelli
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Barrick
authors.forename: Robin
authors.initials: R
authors.lastname: Gold
authors.forename: Susan
authors.initials: S
authors.lastname: Land
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Robert T
authors.initials: RT
authors.lastname: Morris
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tainsky
keywords: cancer genetics; familial cancer predisposition; ovarian cancer; signaling pathway; single nucleotide polymorphism