Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years.

Abstract

Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. In this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G>T transitions and 1 G>A) and one in codon 13 (G>A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2. The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal cancer of later age of onset.

• Authors: Kathryn Alsop, Leeanne Mead, Letitia D Smith, Simon G Royce, Andrea A Tesoriero, Joanne P Young, Andrew Haydon, Garry Grubb, Graham G Giles, Mark A Jenkins, John L Hopper, Melissa C Southey
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 42 Issue 10 Pg. 1357-61 (Jul 2006) ISSN: 0959-8049 [Print] England
• PMID: 16765042 (Publication Type: Journal Article)

Topics

• Adult
• Age Factors
• Colorectal Neoplasms (genetics)
• Female
• Genes, ras (genetics)
• Humans
• Immunohistochemistry
• Male
• Microsatellite Repeats
• Mutation (genetics)