Abstract 259: Analysis of Q356R polymorphism in BRCA1 gene of Jamaican ovarian cancer patients
Authors: Chinnaiyan Aiyavu , Salmon Colleen , Venkatesan Thiagarajan , Levy Arkene , Dhandayuthapani Sivanesan , Rathinavelu Appu 
Published: May 2015

Studies in different populations worldwide have demonstrated that germ line mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancers. In addition, polymorphic variants in these genes have been implicated in an increased breast and ovarian cancer risks. Indeed, it has been known that the germ line mutations in the BRCA1 gene can strikingly increase the life time risk of ovarian cancer by 15-30%. Among BRCA mutations the Q356R polymorphism is a variant causing the amino acid switch from glutamine (Q) to arginine (R) in the putative functional domain of the protein. The present study was carried out to assess the frequency of Q356R polymorphism in BRCA1 gene among Jamaican ovarian cancer patients, since there is lack of data for this population pertaining to this polymorphism. For this analysis the ovarian cancer samples were collected from 23 Jamaican women with 21 benign and 2 malignant tumors. The genomic DNA of cancer samples was extracted and the purity of the DNA was analyzed prior to polymorphism determination. Polymerase chain reaction was performed using the DNA of cancer patients as a template with the primers specific for BRCA1 gene. The Q356R polymorphism status within BRCA1 gene was analyzed through restriction enzyme digestion. The undigested or partially digested arginine (R) coding allele was seen as a band at 211 bp of length, whereas the glutamine (Q) alleles represented by the digestion products were seen at 134 and 77 bp length. The incomplete digestion of R allele indicates a high risk and the digested Q alleles signify the medium or low risk category. Genotyping analyses were performed in all 23 cases using the restriction fragment length analysis. Out of 23 samples, 22 showed digestion fragments of 134 bp and 77 bp, remaining one was partially digested and showed a 211 bp band. Among the samples analyzed the percentage of R allele was (4.34%) and the Q alleles were (95.65%). Our current analysis indicates that the QR genotype frequency for Jamaican women with non-malignant ovarian tumors is only 0.04. However, the QR genotype frequency for Jamaican women with malignant ovarian cancer appears to be 0.5. Thus, functional polymorphisms in BRCA1 might be postulated to be more likely affecting ovarian cancer risk than those in BRCA2. Though the frequency of R allele is only 4.3% in Jamaican population, this polymorphism seems to correlate very well with the malignant status of the tumor. Therefore, patients with this polymorphism can be selected for more aggressive surveillance and therapeutic options. The results presented here are from a small population of Jamaican women with ovarian tumors but further validation of this conclusion can be obtained by conducting a study with larger population of patients (The authors would like to thank the Royal Dames of Cancer Research Inc., Ft. Lauderdale, FL, for their generous support).

Citation Format: Aiyavu Chinnaiyan, Colleen Salmon, Thiagarajan Venkatesan, Arkene Levy, Sivanesan Dhandayuthapani, Appu Rathinavelu. Analysis of Q356R polymorphism in BRCA1 gene of Jamaican ovarian cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 259. doi:10.1158/1538-7445.AM2014-259