title: TGFBR1 and cancer susceptibility.
abstract: 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.
authors.affiliation: Winston Salem, NC.
authors.forename: Boris
authors.initials: B
authors.lastname: Pasche
authors.affiliation: Winston Salem, NC.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pennison
authors.affiliation: Winston Salem, NC.
authors.forename: Hugo
authors.initials: H
authors.lastname: Jimenez
authors.affiliation: Winston Salem, NC.
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse