title: Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk.
abstract: BACKGROUND
  It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways.
  
  
  METHODS
  In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls).
  
  
  RESULTS
  The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (OR per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the "effective" number of markers in stage II (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos, and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, body mass index (BMI) levels, regular aspirin use, or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822.
  
  
  CONCLUSIONS
  Our results provide new evidence of association between PPARG variants and colorectal cancer risk.
  
  
  CONCLUSIONS
  Further replication in independent samples is warranted.
authors.affiliation: Authors' Affiliations: University of Hawaii Cancer Center, Honolulu, Hawaii; Translational Genomics Research Institute, Phoenix, Arizona; Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles; Cancer Prevention Institute of California, Fremont, California; Fred Hutchinson Cancer Research Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; University of Melbourne, Carlton, Victoria, Australia; Cancer Care Ontario, Toronto, Ontario, Canada; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Stanford Cancer Institute, Stanford, California; and National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hansong
authors.initials: H
authors.lastname: Wang
authors.forename: Darin
authors.initials: D
authors.lastname: Taverna
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Fortini
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Terrilea
authors.initials: T
authors.lastname: Burnett
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Robert
authors.initials: R
authors.lastname: Haile
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006254:Hawaii; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
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