Abstract 934: Phospholipase A2A polymorphisms and risk of colorectal neoplasia

Abstract

Abstract Introduction: Pancreatic phospholipase A2 (also known as PLA2G1B or PLA2A) catalyzes the release of fatty acids from dietary phospholipids for adsorption in the small intestine. Some of the polyunsaturated fatty acids removed from the intestinal lumen are precursors to eicosanoids, which are linked to inflammation, cell proliferation and colorectal carcinogenesis. We suspect that genetic variation at the PLA2A locus might affect colorectal neoplasia and thus we evaluated the association of PLA2A tagSNPs with colorectal neoplasia risk in three independent study populations capturing the range of colorectal carcinogenesis. Methods: A linkage-disequilibrium (LD)-based tagSNP selection algorithm (r2=0.90, MAF=4%) identified 3 tagSNPs in PLA2A. We genotyped these SNPs on the same Illumina platform in 3 US population-based case-control studies of colon cancer (1424 cases/1780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). LD was calculated among Caucasian controls for each study. For gene-level associations, we conducted principal components analysis (PCA) and haplotype analysis. Multiple logistic regression was used for single SNPs, adjusting for age, sex, and study center, restricted to Caucasians (>90% of all study populations). Results: Two PLA2A variants were statistically significantly associated with reduced risk of rectal cancer (rs5637, 3702G>A Ser98Ser, p-trend = 0.03 and rs9657930, 1593C>T p-trend = 0.01, see table). Linkage disequilibrium between the SNPs was modest (r2<0.6). Principal component analysis was significant (p=0.02). No statistically significant associations were observed with colon cancer or colorectal polyps overall; however, there was significant heterogeneity by tumor site for polyps (p= 0.01). Conclusion: The results suggest that genetic variability in PLA2A affects susceptibility to rectal but not colon cancer. Additional observational and functional follow-up studies are needed.Table.Selected tagSNPs in PLA2A and risk of rectal cancer, adjusted for age, sex, and study centerSNPGenotypeCasesControlsOR95%CIp (2df)p-trendrs56373702 G>AGG4285361.00.. Ser98SerGA1472150.850.661.08 AA8230.430.190.980.060.03 rs9657930CC4886141.00.. 1593 C>TCT891480.750.561.00 TT3100.390.111.430.050.01 rs2070873GG4365741.00.. 3027 G>TGT1391811.000.781.29 TT6190.420.171.060.150.36Principal component analysis p= 0.02 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 934.