Abstract A110: Associations between genetic variations in inflammation and innate immunity pathways and colorectal cancer

A strong association between chronic inflammation and colorectal cancer (CRC) risk has been observed. We postulated that common variation in genes involved in the inflammation and innate immunity pathways may result in a chronic pro-inflammatory state that may lead to increased CRC risk. We comprehensively examined the associations of 724 tagSNPs in 37 key genes in these pathways with CRC in two large well-characterized studies. The screening phase included 2,322 discordant sibships (2,535 cases, 3,915 unaffected sibling controls) from the Colon Cancer Family Registry. Nineteen gene regions spanned by 99 top hits from main-effect or interaction-effect analyses in phase 1 were followed up by genotyping 351 well-chosen tagSNPs in 4,783 subjects (2,153 cases, 2,630 controls) in five ethnic groups in the Multiethnic Cohort Study. One SNP rs9858822 in PPAR gamma gene was statistically significantly associated with CRC in the replication phase (p=1.5 × 10-4, odds ratio per allele = 1.36), based on a conservative Bonferroni-corrected significance level 0.05 adjusted for the “effective” number of markers (n=306). The risk allele C was common (frequency 0.3) in African Americans but was rare (frequency Citation Format: Hansong Wang, Darin Taverna, Daniel O. Stram, Iona Cheng, Lynne R. Wilkens, Terrilea Burnett, Polly A. Newcomb, Laurence N. Kolonel, Brian E. Henderson, David Duggan, Cornelia M. Ulrich, Loic Le Marchand. Associations between genetic variations in inflammation and innate immunity pathways and colorectal cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A110.