Abstract 5612: Identification of shared regions of genetic susceptibility to breast cancer in Arab and Jewish women with a family history of consanguinity

Abstract

Abstract Background: Breast cancer is the most commonly diagnosed cancer in Israel, and a leading cause of death among women regardless of their ethnic origin. However, younger ages at diagnosis, larger primary tumor size, and lower 5-year survival rate have been reported among Arab women compared with the Jewish women. Arabs have a high rate of parental consanguinity, ranging from 25% to 60% in different countries in the Middle East. Consanguinity leads to a higher probability of sharing alleles identical-by-descent and increased risks for autosomal recessive disorders. Methods: Genome-wide analysis of germline DNA from 32 breast cancer patients and 26 first degree relatives was performed using the Affymetrix Human SNP Array 6.0 or the Illumina CytoSNP12 genotyping platform. Probands were screened for mutations in BRCA1 and BRCA2 to exclude common forms of inherited susceptibility. Genotype data were analyzed using PLINK to screen for runs of homozygosity of at least 500 kilobases. Results: Long runs of homozygosity were observed in five samples, including two consanguineous Arab and 3 Ashkenazi Jewish probands. The largest region of homozygosity was on chromosome 10q23.1-25.3 which harbors several important candidate genes, including the tumor suppressor gene PTEN. Conclusion: Preliminary analysis of breast cancer patients from consanguineous families of Arab or Jewish descent provide suggestive evidence of recessive susceptibility to breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5612. doi:10.1158/1538-7445.AM2011-5612