This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gunter, M. J. Articles by Rothman, N. Search for Related Content PubMed PubMed Citation Articles by Gunter, M. J. Articles by Rothman, N.

Inflammation-Related Gene Polymorphisms and Colorectal Adenoma

¹ Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, NIH, Bethesda, Maryland; ² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York; ³ IARC, Lyon, France; ⁴ German Cancer Research Center, Heidelberg, Germany; and ⁵ Department of Biology and Genetics, University of Pisa, Pisa, Italy

Requests for reprints: Marc Gunter, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail: mgunter{at}aecom.yu.edu

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. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1126–31)

This article has been cited by other articles:

				S. Wilkening, B. Tavelin, F. Canzian, K. Enquist, R. Palmqvist, A. Altieri, G. Hallmans, K. Hemminki, P. Lenner, and A. Forsti Interleukin promoter polymorphisms and prognosis in colorectal cancer Carcinogenesis, June 1, 2008; 29(6): 1202 - 1206. [Abstract] [Full Text] [PDF]

				S. Kim, T. O. Keku, C. Martin, J. Galanko, J. T. Woosley, J. C. Schroeder, J. A. Satia, S. Halabi, and R. S. Sandler Circulating Levels of Inflammatory Cytokines and Risk of Colorectal Adenomas Cancer Res., January 1, 2008; 68(1): 323 - 328. [Abstract] [Full Text] [PDF]

				C. C. Reyes-Gibby, M. Spitz, X. Wu, K. Merriman, C. Etzel, E. Bruera, R. Kurzrock, and S. Shete Cytokine Genes and Pain Severity in Lung Cancer: Exploring the Influence of TNF-{alpha}-308 G/A IL6-174G/C and IL8-251T/A Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2745 - 2751. [Abstract] [Full Text] [PDF]

				K. L. Margolis, R. J. Rodabough, C. A. Thomson, A. M. Lopez, A. McTiernan, and for the Women's Health Initiative Research Group Prospective Study of Leukocyte Count as a Predictor of Incident Breast, Colorectal, Endometrial, and Lung Cancer and Mortality in Postmenopausal Women Arch Intern Med, September 24, 2007; 167(17): 1837 - 1844. [Abstract] [Full Text] [PDF]