Abstract LB-356: Catalase and NADPH oxidase single nucleotide polymorphisms are associated with increased risk and serve as potential targets for breast and ovarian cancers.

Abstract

Abstract We investigated the association of a SNP in catalase (CAT) and in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22-phox subunit with an increased risk of development of ovarian and breast cancers. Both enzymes play major roles in the regulation of the redox balance. In the general population, the minor allele frequency (MAF) for CAT SNP C-262T (rs1001179) is 12.4% and 30.3%for NADPH oxidase SNP C242T (rs4673). The risk of breast cancer has been associated with decreased activity of CAT, which was attributed to this specific SNP. Similarly, an increase in NADPH oxidase activity has been associated with specific SNP in the CYBA gene, encoding the p22-phox subunit of NAPDH oxidase, substituting allele C with T at position 242 located on chromosome 16q24. Patients (n=190) were recruited from the Karmanos Cancer Institute, Detroit, MI for genetic counseling based on personal and family histories. Stored blood samples were subjected to DNA extraction (QIAamp DNA mini kit) followed by TaqMan® SNP Genotyping Assay Sets for rs1001179 or rs4673 run on the QuantStudio™ 12K Flex Real-Time PCR System. Data were analyzed using SPSS for Mac V.21, utilizing Chi-squared and regression analysis with p<0.05 considered statistically significant. Patients were 92.1% female and 7.3% male. Age range (minimum-maximum) was 72 (18-90), and median was 51 ± 13.5. The racial distribution was 92.1% White, 5.2% Black and 0.5% Asian. A primary cancer was present or develops in 51.8% of which 59% had any form of cancer of the breast, 40% ovarian and 1% of the lung and bronchus. The genotype frequency for the CAT SNP was: CC= 60.3%; CT= 37.0% and TT= 2.7%. Data was not reported in 1 of the cases, estimated at 1% of the cohort. The mutant allele was present at a frequency of 39.7% as compared to 12.4% in the general population and was statistically significant (Chi-Square=51, p<0.05, two-tailed). The genotype frequency for the NADPH oxidase SNP was: CC= 32.6%, CT= 49.5%, and TT=17.9%. Similarly, the frequency for the NADPH oxidase was 67.4% as compared to 30.3% in the general population, Chi-Square=112, p<0.05, two-tailed. BRCA1/2 status was available for 91.6% of the individuals. Seven of ovarian (n=36) and 18 of breast cancer (n=51) and 25 of the no cancer (86) patients were BRCA1/2 positive. Multiple logistic regressions adjusted for sex, race, age at primary diagnostic in both BRCA1/2 positive (cases) and negative (controls), was unable to detect statistically significant predictive power for the SNP variants included in the models, likely due to small sample size. CAT SNP, OR (95% CI)=1.456 (.666-3.184), p=0.347; CYBA SNP, OR (95% CI)=1.060 (.396-2.835), p=0.908. Our findings suggest that both the CAT C-262T SNP and NADPH oxidase C242T SNP could be used in risk stratification for patients affected by either breast or ovarian cancers. Citation Format: Jimmy Belotte, Nicole M. Fletcher, Nancy K. Levin, Michael S. Simon, Husam M. Abu-Soud, Michael P. Diamond, Michael A. Tainsky, Ghassan M. Saed. Catalase and NADPH oxidase single nucleotide polymorphisms are associated with increased risk and serve as potential targets for breast and ovarian cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-356. doi:10.1158/1538-7445.AM2013-LB-356 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.