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- Title
Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk.
- Authors
Schwab, R.; Bussolari, R.; Corvetta, D.; Chayka, O.; Santilli, G.; Kwok, J. M.-M.; Amorotti, G. F.; Tonini, G. P.; Iacoviello, L.; Bertorelle, R.; Menin, C.; Hubank, M.; Calabretta, B.; Sala, A.
- Abstract
The B-MYB proto-oncogene is a transcription factor belonging to the MYB family that is frequently overexpressed or amplified in different types of human malignancies. While it is suspected that B-MYB plays a role in human cancer, there is still no direct evidence of its causative role. Looking for mutations of the B-MYB gene in human cell lines and primary cancer samples, we frequently isolated two nonsynonymous B-MYB polymorphic variants (rs2070235 and rs11556379). Compared to the wild-type protein, the B-MYB isoforms display altered conformation, impaired regulation of target genes and decreased antiapoptotic activity, suggesting that they are hypomorphic variants of the major allele. Importantly, the B-MYB polymorphisms are common; rs2070235 and rs11556379 are found, depending on the ethnic background, in 10–50% of human subjects. We postulated that, if B-MYB activity is important for transformation, the presence of common, hypomorphic variants might modify cancer risk. Indeed, the B-MYB polymorphisms are underrepresented in 419 cancer patients compared to 230 controls (odds ratio 0.53; (95%) confidence interval 0.385–0.755; P=0.001). This data imply that a large fraction of the human population is carrier of B-MYB alleles that might be associated with a reduced risk of developing neoplastic disease.Oncogene (2008) 27, 2929–2933; doi:10.1038/sj.onc.1210947; published online 19 November 2007
- Subjects
PROTO-oncogenes; CANCER risk factors; GENETIC polymorphisms; GENETIC disorders; CANCER cells; CONNECTIVE tissue cells; CANCER patients
- Publication
Oncogene, 2008, Vol 27, Issue 20, p2929
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210947