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Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer

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Abstract

Objective and methods

The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression.

Results

Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53–1.18) or two (OR, 0.58; 95% CI, 0.35–0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p trend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer.

Conclusions

Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer.

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Acknowledgments

We appreciate the continued efforts of the staff members at the Johns Hopkins George W. Comstock Center for Public Health Research and Prevention in the conduct of the CLUE II study.

Financial support

This research was supported by a grant from the American Institute for Cancer Research. Konstantinos Tsilidis was funded by a J. William Fulbright grant and a scholarship from the Hellenic State Scholarships Foundation.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Rm E6132, Baltimore, MD, 21205, USA

    Konstantinos K. Tsilidis, Kathy J. Helzlsouer, Judith Hoffman-Bolton, Sandra L. Clipp, Kala Visvanathan & Elizabeth A. Platz

  2. Prevention and Research Center, Weinberg Center for Women’s Health and Medicine, Mercy Medical Center, Baltimore, MD, USA

    Kathy J. Helzlsouer

  3. George W. Comstock Center for Public Health Research and Prevention, Johns Hopkins Bloomberg School of Public Health, Hagerstown, MD, USA

    Kathy J. Helzlsouer, Judith Hoffman-Bolton & Sandra L. Clipp

  4. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Kathy J. Helzlsouer, Kala Visvanathan & Elizabeth A. Platz

  5. Genetics and Genomics, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD, USA

    Michael W. Smith

  6. Laboratory of Molecular Technology, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD, USA

    Victoriya Grinberg

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  1. Konstantinos K. Tsilidis
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Correspondence to Elizabeth A. Platz.

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Tsilidis, K.K., Helzlsouer, K.J., Smith, M.W. et al. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control 20, 1739–1751 (2009). https://doi.org/10.1007/s10552-009-9427-7

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