Lack of an Association between the TGFBR1*6A Variant and Colorectal Cancer Risk
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% CI) 0.83 1.32] 0.82 (95% CI, 0.34 1.99) and 0.92 (95% CI, 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% CI, 0.64 2.24) for homozygosity, 1.11 (95% CI, 0.96 1.29) for heterozygosity, and 1.13 (95% CI, 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.
Clinical Cancer Research