The role of SMAD4 in early-onset colorectal cancer

Royce, S.G., Alsop, K., Haydon, A., Mead, L., Smith, L.D., Tesoriero, A.A., Giles, G.G., Jenkins, M.A., Hopper, J.L., and Southey, M.C. (2010) The role of SMAD4 in early-onset colorectal cancer. Colorectal Disease, 12 (3). pp. 213-219.

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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.

Item ID: 35578
Item Type: Article (Research - C1)
ISSN: 1463-1318
Keywords: early-onset colorectal cancer, SMAD4, 18q, copy number
Funders: National Health and Medical Research Council (NHMRC)
Date Deposited: 01 Oct 2014 15:51
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111203 Cancer Genetics @ 75%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110316 Pathology (excl Oral Pathology) @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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