Carcinogenesis Advance Access published online on July 5, 2007
Carcinogenesis, doi:10.1093/carcin/bgm155
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Published by Oxford University Press 2007.
Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
2 SAIC-Frederick, NCI-FCRDC, Frederick, Maryland
3 Department of Epidemiology and the University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
4 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
This research was supported by the Intramural Research Program of the National Cancer Institute (NCI), National Institutes of Health. Address correspondence and reprint requests to: Sonja Berndt, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8012, MSC 7240, Bethesda, MD, 20892-7240, E-mail: berndts{at}mail.nih.gov
Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine that has been implicated in the pathogenesis of colorectal neoplasia. To investigate the association between genetic variants in TGFB1 and the risk of colorectal adenoma, we conducted a case-control study of 754 advanced adenoma cases and 769 controls from the baseline screening exam of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma (
1 cm, high-grade dysplasia, or villous characteristics), and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy. DNA was extracted from blood specimens, and five single nucleotide polymorphisms in TGFB1 of known or suggested functional significance (-800G>A, -509C>T, Leu10Pro, Arg25Pro, and Thr263Ile) were genotyped. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between each polymorphism and adenoma. The high TGFB1 producer genotypes, -509TT and 10Pro/Pro, were associated with an increased risk of colorectal adenoma compared to other genotypes (OR = 1.51, 95% CI: 1.04-2.20 and OR = 1.37, 95% CI: 1.02-1.86, respectively). These increased risks, particularly for -509TT, were greater for persons with multiple adenomas (OR = 1.89, 95% CI: 1.16-3.09, P = 0.01) and individuals with rectal adenoma (OR = 2.95, 95% CI: 1.66-5.26, P = 0.0002). Haplotype analysis revealed similar findings under a recessive model. No associations were observed for polymorphisms at codons 25 and 263. In conclusion, variants which enhance TGFB1 production may be associated with an increased risk of advanced colorectal adenoma.
Key Words: transforming growth factor beta 1 • colorectal neoplasia • adenoma • polymorphism • growth factor
Received April 30, 2007; revised June 13, 2007; accepted June 26, 2007.
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