title: C-reactive protein genotypes and haplotypes, polymorphisms in NSAID-metabolizing enzymes, and risk of colorectal polyps.
abstract: BACKGROUND
  C-reactive protein (CRP) is a nonspecific marker of inflammation linked to cardiovascular disease and possibly colon cancer. Polymorphisms in CRP have been associated with differential CRP concentrations among healthy adults, with some evidence for functional effects on CRP expression.
  
  
  METHODS
  A linkage disequilibrium-based tag single nucleotide polymorphism (SNP)-selection algorithm identified six tagSNPs for Europeans (-821A>G, -390C>T/A, 90A>T, 838G>C, 2043G>A, and 4363C>A), defining six haplotypes with more than 1% frequency. In a case-control study of adenomatous (n=491) or hyperplastic (n=184) polyps versus polyp-free controls (n=583) we investigated these SNPs in relation to colorectal polyp risk.
  
  
  RESULTS
  Individuals with 838 GC or CC genotypes had a modestly, although not statistically significantly, increased risk of adenomas (odds ratio: 1.4 95% confidence interval: 0.9-2.1) and a nearly 2-fold increased risk of concurrent adenomas and hyperplastic polyps (odds ratio: 2.0 95% confidence interval: 1.1-3.6). Increased risk for concurrent adenomas and hyperplastic polyps was also observed for haplotype ACACAC. No other main associations were detected. Risk of adenomas associated with 2043G>A differed with nonsteroidal anti-inflammatory drug (NSAID) use. Among NSAID nonusers, there was a suggestion that the GA or AA genotypes were associated with decreased risk of adenomas; this was not seen among NSAID users (P interaction=0.03). We also observed interactions between UGT1A1 [TA](7) promoter repeat polymorphism and CRP tagSNPs -390C>T/A and 90A>T, in which only the homozygous variant CRP genotype was associated with increased risk of adenoma among those with the UGT1A1 6rpt/6rpt genotype (P interaction=0.02 and 0.04 for -390C>T/A and 90A>T, respectively).
  
  
  CONCLUSIONS
  These results provide limited support for associations between genetic variation in CRP and colorectal polyp risk. The observed interactions should be evaluated further.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, University of Washington, Seattle, Washington, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.forename: Jeannette
authors.initials: J
authors.lastname: Bigler
authors.forename: John
authors.initials: J
authors.lastname: Whitton
authors.forename: Justin G
authors.initials: JG
authors.lastname: Sibert
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007417:Intestinal Polyps / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000099148:UGT1A1 Enzyme
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001189:Aryl Hydrocarbon Hydroxylases; D002097:C-Reactive Protein; D065729:Cytochrome P-450 CYP2C9; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C450260:CYP2C9 protein, human