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- Title
The role of SMAD4 in early-onset colorectal cancer.
- Authors
Royce, S. G.; Alsop, K.; Haydon, A.; Mead, L.; Smith, L. D.; Tesoriero, A. A.; Giles, G. G.; Jenkins, M. A.; Hopper, J. L.; Southey, M. C.
- Abstract
Objective Chromosomal loss within the region of 18q and loss of SMAD4 expression have been reported to be frequent somatic events during colorectal cancer tumour progression; however, their associations with age at onset have not been widely studied. Method We analysed 109 tumours from a population-based case-family study based on colorectal cancers diagnosed before the age of 45 years. These patients with early-onset colorectal cancer had been previously screened for germ-line mismatch repair gene mutations, microsatellite instability (that included the mononucleotide repeat in TGFβRII) and somatic k-ras mutations. We measured SMAD4 protein expression using immunohistochemistry and SMAD4 copy number using quantitative real-time PCR. Results Loss of SMAD4 protein expression was observed in 27/109 (25%) of cancers tested and was more commonly observed in rectal tumours (15/41, 36%) when compared with tumours arising in the colon (11/66, 17%) ( P = 0.04). There was no association between SMAD4 protein expression and TGFβR11 mutation status, SMAD4 copy number, family history, MSI status, tumour stage or grade. Conclusion Loss of SMAD4 expression is a common feature of early-onset colorectal tumours as it is in colorectal cancers diagnosed in other age-groups. Taken together, the molecular pathways (genetic and epigenetic) now known to be involved in early-onset colorectal cancer only explain a small proportion of the disease and require further exploration.
- Subjects
COLON cancer; ANAL cancer; TUMOR growth; DNA damage; MUTAGENESIS; GENE expression; CANCER patients
- Publication
Colorectal Disease, 2010, Vol 12, Issue 3, p213
- ISSN
1462-8910
- Publication type
Article
- DOI
10.1111/j.1463-1318.2009.01779.x