Uncommon TGFBRI allele is not associated with increased susceptibility to colon cancer.

Previous studies have suggested that an allele of the transforming growth factor-beta type I receptor (TGFBRI) gene that codes for six instead of the usual nine alanines in a polyalanine repeat is associated with an increased susceptibility to colon cancer, and that the six-alanine homozygote is seen only in individuals with some form of cancer. We evaluated this TGFBRI polymorphism in a population-based sample of 252 individuals with colon cancer and 362 age- and gender-matched controls from the state of Utah. TGFBRI genotypes were determined by PCR amplification and length determination of the polyalanine repeat. In addition to the common nine-alanine (9A) allele, we identified six- (6A), eight- (8A), ten- (10A), eleven- (11A), and twelve-alanine (12A) TGFBRI alleles. 6A/9A heterozygotes were seen in similar percentages of colon cancer cases (18.3%) and controls (16.0%). 6A/6A homozygotes were slightly more common in controls than in colon cancer cases (1.4% vs. 0.8%), and none of the controls with the 6A/6A genotype had any of the non-colonic cancers reported in previous studies. We conclude that the 6A TGFBRI allele is not associated with an increased susceptibility to colon cancer at the population level, and that the 6A/6A homozygote is not restricted to individuals with some form of cancer. Copyright 2001 Wiley-Liss, Inc.