Debate about TGFBR1 and the susceptibility to colorectal cancer

Recent years have witnessed enormous progress in our understanding of the genetic predisposition to colorectal cancer (CRC). Estimates suggest that all or most genetic susceptibility mechanisms proposed so far, ranging from high-penetrance genes to low-risk alleles, account for about 60% of the population-attributable fraction of CRC predisposition. In this context, there is increasing interest in the gene encoding the transforming growth factor β receptor 1 (TGFBR1); first when over a decade ago a common polymorphism in exon 1 (rs11466445, TGFBR1*6A/9A) was suggested to be a risk allele for CRC, then when linkage studies identified the chromosomal region where the gene is located as susceptibility locus for familial CRC, and more recently when the allele-specific expression (ASE) of the gene was proposed as a risk factor for CRC. Published data on the association of TGFBR1 with CRC, regarding polymorphisms and ASE and including sporadic and familial forms of the disease, are often contradictory. This review gives a general overview of the most relevant studies in order to clarify the role of TGFBR1 in the field of CRC genetic susceptibility.