title: Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia.
abstract: Pancreatic phospholipase A2, product of PLA2G1B, catalyzes the release of fatty acids from dietary phospholipids.Diet is the ultimate source of arachidonic acid in cellular phospholipids, precursor of eicosanoid signaling molecules, linked to inflammation, cell proliferation and colorectal carcinogenesis. We evaluated the association of PLA2G1B tagging single-nucleotide polymorphisms with colorectal neoplasia risk. A linkage-disequilibrium-based tagSNP algorithm (r(2)=0.90, MAF≥4%) identified three tagSNPs. The SNPs were genotyped on the Illumina platform in three population-based, case-control studies: colon cancer (1424 cases/1780 controls); rectal cancer (583/775); colorectal adenomas (485/578). Evaluating gene-wide associations, principal-component and haplotype analysis were conducted, individual SNPs were evaluated by logistic regression. Two PLA2G1B variants were statistically significantly associated with reduced risk of rectal cancer (rs5637, 3702 G>A Ser98Ser, p-trend=0.03; rs9657930, 1593 C>T, p-trend=0.01); principal component analysis showed that genetic variation in the gene overall was statistically significantly associated with rectal cancer (p=0.02). NSAID users with the rs2070873 variant had a reduced rectal cancer risk (P-inter=0.02). Specific associations were observed with tumor subtypes (TP53/KRAS). The results suggest that genetic polymorphisms in PLA2G1B affect susceptibility to rectal cancer.
authors.affiliation: National Center for Tumor Diseases/German Cancer Research Center Im Neuenheimer Feld 460, 69120 Heidelberg,Germany.
authors.forename: Clare
authors.initials: C
authors.lastname: Abbenhardt
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kulmacz
authors.forename: Liren
authors.initials: L
authors.lastname: Xiao
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Galbraith
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: Lisel
authors.initials: L
authors.lastname: Koepl
authors.forename: Robert W
authors.initials: RW
authors.lastname: Owen
authors.forename: Dominique
authors.initials: D
authors.lastname: Scherer
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
keywords: Phospholipase A2G1B; case-control study; colorectal neoplasia; polymorphism
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