title: Linkage disequilibrium and haplotype analysis of COX-2 and risk of colorectal adenoma development.
abstract: Single nucleotide polymorphisms (SNPs) in the promoter and untranslated region of cyclooxygenase (COX)-2, an inducible enzyme responsible for the synthesis of prostaglandins, have been reported to modulate the risk for many human cancers. We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of 13 single nucleotide polymorphisms of the COX-2 gene and examined its susceptibility to adenoma development in 72 African American cases and 142 controls. Results revealed significant variation in LD patterns with consequence for adenoma development. Two distinct haplotype blocks were identified; one block covered the coding regions of exon 1, introns and a section of the 3'-unstranslated region (3'-UTR), whereas the second block resided solely in the 3'-UTR region. A haplotype in block 1 increased the risk of adenoma development by threefold (odds ratio [OR]= 2.9, confidence interval [CI]= 1.8-3.7, P= 0.002). Regression analysis showed, increase in copies of minor alleles of 6,064(T>C) polymorphism associated with increased odds of adenoma development by 80% (OR = 1.80, CI = 1.09-3.21, P= 0.034), 10,848(G>A) by 84% (OR = 1.84, CI = 1.05-3.23, P= 0.034) and 10,935(A>G) by 32% (OR = 1.32, CI = 1.12-3.69, P= 0.036). These results support the hypothesis that COX-2 gene might play a role in the etiology of colon cancer and warrant further investigation in other cancers. Besides, these variations should be taken into account for disease-based association studies in which the COX-2 polymorphism is considered as a candidate gene. Clin Trans Sci 2012; Volume 5: 60-64.
authors.affiliation: Georgetown-Howard University Center for Clinical and Translational Science and Department of Family Medicine, Howard University College of Medicine, Washington, USA. jkwagyan@howard.edu
authors.forename: John
authors.initials: J
authors.lastname: Kwagyan
authors.forename: Victor
authors.initials: V
authors.lastname: Apprey
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
mesh_terms: D020413:3' Untranslated Regions; D000236:Adenoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018256:Adenomatous Polyps / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D016022:Case-Control Studies; D003111:Colonic Polyps / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004219:District of Columbia / Q000453:epidemiology; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human