Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis

Objective Group IVA cytosolic phospholipase A 2 (cPLA 2 α) plays a key role in tumorigenesis via generating arachidonic acids as the substrate of cyclooxygenase. The aim of this study was to elucidate the possible associations between cPLA 2 α gene polymorphisms and phenotypic features of patients with familial adenomatous polyposis (FAP). Patients and Methods A tag single nucleotide polymorphisms (SNPs)-based genotype–phenotype association study of the cPLA 2 α gene was conducted in 73 Japanese patients from 59 families with FAP. Based on the HapMap database, seven tag SNPs of the cPLA 2 α gene were selected and genotyped by direct sequencing analysis. The genotype–phenotype association in relation to the adenomatous polyposis coli ( APC ) gene mutation was also assessed. Results The single SNP analysis showed that rs3820185 C allele [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–4.9] and rs127446200 GG genotype (OR, 10.9; 95%CI, 1.6–69.8), were more frequent in patients with gastric fundic gland polyposis (FGP) than in those without. Rs12749354 C allele was more frequently found in patients with small intestinal adenoma (OR, 7.0; 95% CI, 1.5–30.4; p = 0.008). This association was also significant when adjusted for covariates (age, sex, and APC mutation) in a logistic regression analysis (adjusted OR, 7.4; 95% CI, 1.2–64.2; p = 0.027). Conclusions The cPLA 2 α gene may be a possible disease modifier gene in FAP.