TGFBR1 and cancer susceptibility

Transforming growth factor beta (TGF-β) is a potent inhibitor of cell growth. TGFBR1 6A is a polymorphism consisting of a 9-base pair in-frame deletion within exon 1 of the type I TGF-β receptor (TGFBR1), which results in a receptor with decreased TGF-β signaling capability. The discovery of an asso...

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Bibliographic Details
Published in:Transactions of the American Clinical and Climatological Association 2014, Vol.125, p.300-312
Main Authors: Pasche, Boris, Pennison, Michael J, Jimenez, Hugo, Wang, Minghui
Format: Article
Language:English
Subjects:
Animals
Biomarkers, Tumor - deficiency
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Genetic Predisposition to Disease
Humans
Mice, Knockout
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Phenotype
Protein-Serine-Threonine Kinases - deficiency
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Receptors, Transforming Growth Factor beta - deficiency
Receptors, Transforming Growth Factor beta - genetics
Receptors, Transforming Growth Factor beta - metabolism
Risk Factors
Signal Transduction
Transforming Growth Factor beta - metabolism
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Summary:Transforming growth factor beta (TGF-β) is a potent inhibitor of cell growth. TGFBR1 6A is a polymorphism consisting of a 9-base pair in-frame deletion within exon 1 of the type I TGF-β receptor (TGFBR1), which results in a receptor with decreased TGF-β signaling capability. The discovery of an association between TGFBR1*6A and cancer susceptibility led to the hypothesis that hypomorphic variants of the TGF-β signaling pathway may predispose to the development of cancer. This hypothesis was tested in vivo with the development of a mouse model of Tgfbr1 haploinsufficiency. Tgfbr1 (+/-) mice developed twice as many intestinal tumors as Tgfbr1 (+/+). Tgfbr1 haploinsufficiency was also associated with early onset adenocarcinoma and increased tumor cell proliferation. A case control study identified two haplotypes associated with constitutively decreased TGFBR1 and substantially increased colorectal cancer risk indicating that TGFBR1 may act as a potent modifier of cancer risk.
ISSN:0065-7778