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Background: Transforming growth factor-[beta]1 (TGFb1) is a multifunctional signalling molecule with a wide array of roles. Animal experiments suggest that TGFb1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting malignant transformation of those growths that do develop. A polymorphism in the signal peptide sequence of the TGF[beta]1 gene (L10P) has been associated with increased levels of plasma TGFb1 in individuals with the P allele.

Methods: We investigated whether this polymorphism was associated with the risk of colorectal adenomatous or hyperplastic polyps in a case-control study of individuals from Minnesota. Risk of colorectal polyps was evaluated separately for individuals with adenomatous polyps (n=513) and hyperplastic polyps (n=191) relative to polyp-free controls (n=606) using logistic regression analysis.

Results: No overall association was seen between the L10P polymorphism and risk of colorectal adenomatous polyps. The age- and sex-adjusted odds ratios (OR) of developing colorectal hyperplastic polyps were 1.0 (95% CI: 0.7, 1.4) and 0.7 (95% CI: 0.4, 1.1) for individuals with the LP and PP genotypes, respectively, compared with individuals with the LL genotype. When stratified by smoking, evidence for a decreased risk of hyperplastic polyps associated with the P allele was seen only among ever smokers (P for trend=0.05).

Conclusions: Whereas adenoma risk did not vary by TGF[beta]1 L10P genotype, these results suggest that the L10P variant allele may have a protective role in the development of colorectal hyperplastic polyps, possibly consistent with its role as an inhibitor of epithelial growths.

(C) Copyright Oxford University Press 2004.