Abstract B22: BRCA1 and BRCA2 mutational spectra in African American men with prostate cancer

Abstract

Abstract Introduction: Mutations in BRCA1/2 increase the risk of breast and ovarian cancer. Notably, in studies of Ashkenazi Jewish men, BRCA1/2 mutations have also been found to increase the risk of prostate cancer. Fortunately, for men and women with unequivocal BRCA1/2 mutations, treatment guidelines are available consequently leading to improved outcomes. Given the high incidence and mortality rates of prostate cancer (PCa) in African American men, we sought to determine impact, as well as the mutational spectra of BRCA1 and BRCA2 in African American men with hereditary prostate. Methods: For this study, DNA from PCa patients with and without a family history of breast (n=9) or ovarian (n=2) (OvCa) cancer were interrogated using targeted next generation sequencing of BRCA1 and BRCA2 coding region and exon-intron boundaries. Fifteen individual samples (mean age= 56.47 years; Range= 45-71 years) were sequenced along with a 16th sample which contained a pool of 25 individuals (mean age=59.17 years; Range=50-69 years) with no reported family history of breast or ovarian cancer. Results: Next generation sequencing results displayed 776,731 read with an average of 133 base pairs per read. There was a minimum coverage of 100x with an average of 250x; each sample averaged 13 variants. There were 205 (15.5%) heterozygous and homozygous variant calls for which 197 (96.1%) were SNPs and 8 (3.9%) were deletions. Specifically, 131 (63.9%) and 74 (36.1%) variants were found in BRCA2 and BRCA1, respectively. Of the 48 unique variants, 14 (29.2%) were found in exons. Importantly, 7 (46.67%) of the exonic variants, mainly rs766173, rs180426, rs144848, rs1799944, rs2227943, 37218874, and rs4986850, were differentially found in those with a family history of BCa or OvCa compared to those without. In particular, rs766173, rs180426, rs1799944, and rs37218874 variants were found in those who reported a family history of BCa or OvCa, although the frequencies were low. Of the 7 exonic variants, 2 were potentially damaging as determined by bioinformatics analysis, 3 were likely benign, and 2 were variants of unknown significance. However, none were unequivocally pathogenic. Conclusions: Like their African American breast cancer counterparts, the impact of BRCA1 and BRCA2 on prostate cancer remains unknown due to the high frequency of variants of unknown significance. Therefore, functional studies of these variants are warranted. The identification of genetic and molecular mechanisms associated with carcinogenesis will allow clinicians to personalize prevention, management, and treatment strategies. Citation Format: Cha'Tonya Brown, John McDonald, Muneer Abbas, Georgia Dunston, Yasmine Kanaan, Luisel Ricks-Santi. BRCA1 and BRCA2 mutational spectra in African American men with prostate cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B22.