Inflammation-related gene polymorphisms and colorectal adenoma.
Chronic inflammation has been reported to be a risk factor for colorectal neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with colorectal adenoma, a precursor of colorectal cancer. We investigated the association of colorectal adenoma with 19 single nucleotide polymorphisms in a range of important proinflammatory (IL1B, IL6, IL8, TNF, and LTA) and anti-inflammatory (IL4, IL10, and IL13) cytokines and other inflammation-related genes (PTGS2 and PPARG) in a case-control study of risk factors for colorectal polyps in which all participants (ages 18-74 years) had undergone colonoscopy or sigmoidoscopy. The study sample comprised 244 cases of colorectal adenoma and 231 polyp-free controls. Compared with being homozygous for the common allele, heterozygosity at the IL1B -31 (C>T) locus was associated with an odds ratio (OR) for colorectal adenoma of 1.8 [95% confidence interval (95% CI), 1.2-2.9]. Homozygous carriers of the IL8 -251-A allele were at 2.7-fold increased risk of adenoma (95% CI, 1.5-4.9) compared with homozygosity for the common T allele, whereas carriage of at least one IL8 -251-A allele conferred a 1.5 increased odds of disease (95% CI, 1.0-2.4). Among non-nonsteroidal anti-inflammatory drug users, there was a statistically significant association between the IL10 -819-T/T genotype and adenoma compared with the common IL10 -819-C/C genotype (OR, 3.9; 95% CI, 1.1-13.6), which was not evident among nonsteroidal anti-inflammatory drug users (OR, 0.7; 95% CI, 0.3-1.5; P(interaction) = 0.01). These exploratory data provide evidence that polymorphic variation in genes that regulate inflammation could alter risk for colorectal adenoma.
Gunter
Marc J
MJ
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA. mgunter@aecom.yu.edu
Canzian
Federico
F
Landi
Stefano
S
Chanock
Stephen J
SJ
Sinha
Rashmi
R
Rothman
Nathaniel
N
D018256:Adenomatous Polyps / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015996:Survival Rate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D016207:Cytokines