Variants in the Signaling Protein TSAd are Associated with Susceptibility to Ovarian Cancer in BRCA1/2 Negative High Risk Families

• Main Authors: Ludmila Kaplun, Aviva Levine Fridman, Wei Chen, Nancy K. Levin, Sidra Ahsan, Nancie Petrucelli, Jennifer L. Barrick, Robin Gold, Susan Land, Michael S. Simon, Robert T. Morris, Adnan R. Munkarah, Michael A. Tainsky
• Format: Article
• Language: English
• Published: SAGE Publishing 2012-01-01
• Series: Biomarker Insights
• Online Access: https://doi.org/10.4137/BMI.S10815

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.