TY - JOUR
T1 - Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk
AU - Wang, Hansong
AU - Taverna, Darin
AU - Stram, Daniel O.
AU - Fortini, Barbara K.
AU - Cheng, Iona
AU - Wilkens, Lynne R.
AU - Burnett, Terrilea
AU - Makar, Karen W.
AU - Lindor, Noralane M.
AU - Hopper, John L.
AU - Gallinger, Steve
AU - Baron, John A.
AU - Haile, Robert
AU - Kolonel, Laurence N.
AU - Henderson, Brian E.
AU - Newcomb, Polly A.
AU - Casey, Graham
AU - Duggan, David
AU - Ulrich, Cornelia M.
AU - Le Marchand, Loïc
PY - 2013/11
Y1 - 2013/11
N2 - 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 1/4 1.36, Bonferroni-adjusted P 1/4 0.045), based on the "effective" number of markers in stage II (n 1/4 306). 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.
AB - 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 1/4 1.36, Bonferroni-adjusted P 1/4 0.045), based on the "effective" number of markers in stage II (n 1/4 306). 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.
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U2 - 10.1158/1055-9965.EPI-13-0694
DO - 10.1158/1055-9965.EPI-13-0694
M3 - Article
C2 - 24045924
AN - SCOPUS:84887302446
SN - 1055-9965
VL - 22
SP - 2094
EP - 2101
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 11
ER -