Lack of an association between the TGFBR1*6A variant and colorectal cancer risk

Abstract

Purpose: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies. Experimental Design: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted. Results: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% Cl), 0.83-1.32], 0.82 (95% Cl, 0.34-1.99), and 0.92 (95% Cl, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% Cl, 0.64-2.24) for homozygosity, 1.11 (95% Cl, 0.96-1.29) for heterozygosity, and 1.13 (95% Cl, 0.98-1.30) for carriers of TGFBR1*6A. Conclusion: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer. © 2007 American Association for Cancer Research.