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Int J Mol Epidemiol Genet 2013;4(3):140-149

Original Article
Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia

Clare Abbenhardt, Elizabeth M Poole, Richard J Kulmacz, Liren Xiao, Karen Curtin, Rachel L Galbraith, David Duggan, Li Hsu,
Karen W Makar, Bette J Caan, Lisel Koepl, Robert W Owen, Dominique Scherer, Christopher S Carlson, Genetics and
Epidemiology of Colorectal Cancer Consortium (GECCO) and CCFR, John D Potter, Martha L Slattery, Cornelia M Ulrich
National Center for Tumor Diseases/German Cancer Research Center, Im Neuenheimer Feld 460, 69120 Heidelberg,
Germany; Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, PO Box 19024, Seattle, WA, USA; Channing
Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston MA
02115, USA; University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA; Department
of Medicine, School of Medicine, University of Utah, 30 N. 1900 E., Salt Lake City, UT 84132, USA; Translational Genomics
Research Institute, 445 N Fifth St, Phoenix, AZ 85004, USA; Department of Research, Kaiser Permanente Medical Research
Program, 2000 Broadway, Oakland, CA 94612, USA; Centre for Public Health Research, Massey University, PO Box 756,
Wellington, New Zealand; Department of Epidemiology, University of Washington, PO Box 357236, Seattle, WA 98195, USA

Received June 23, 2013; Accepted July 28, 2013; Epub September 12, 2013; Published September 15, 2013

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 (r2=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. (IJMEG1306005).

Keywords: Phospholipase A2G1B, polymorphism, colorectal neoplasia, case-control study

Address correspondence to: Dr. Cornelia Ulrich, National Center for Tumor Diseases (NCT) and German Cancer Research
Center (DKFZ), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. E-mail: neli.ulrich@nct-heidelberg.de