Abstract IA11A: Tumor heterogeneity: Making the most of diversity.

Initial genome wide association studies (GWAS) of common cancers focused on combining all available cases in order to maximize the statistical power of the studies. While many genome wide significant associations (p < 5 × 10−8) were observed, this approach overlooked the possibility that certain genetic risk factors might have greater effects in specific populations. With this in mind more recent studies have focused on associations between common genetic variants and disease in populations other than those of northern European ancestry. In addition, GWAS of predisposed individuals, such as carriers of BRCA1 and BRCA2 mutations, have been conducted based on the hypothesis that unique modifiers of breast and ovarian cancer risk might influence disease in these populations. More recently, associations with histological subtypes of tumors have been observed for a number of different cancer types. In the setting of breast cancer, specific associations with estrogen receptor status of tumors and even triple negative tumors (estrogen receptor, progesterone receptor, and HER2 negative) have been reported. Ongoing studies further suggest that specific associations with histochemical markers and tumor grade may also exist in the general population. Here we will discuss recent associations between genetic variants and subpopulations of disease using breast cancer as a model, and consider the importance of these findings for an improved understanding of the etiology of breast cancer and enhanced cancer risk assessment.

Citation Format: Fergus J. Couch. Tumor heterogeneity: Making the most of diversity. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA11A.