NEW YORK (Reuters Health) - Although MSH6 mutations increase the risk of hereditary nonpolyposis colorectal cancer in both men and women, men with this mutation of the mismatch repair gene appear to have a risk similar to that known to be caused by other such mutations, researchers report in July issue of Gastroenterology.
As lead investigator Dr. Yvonne M. C. Hendriks told Reuters Health, “in families with a pathogenic MSH6 mutation we recommend the same colonoscopic surveillance protocol in male carriers of an MSH6 mutation as recommended in MLH1 and MSH2 mutation carriers because the cumulative risks did not differ significantly from the risk in MLH1 and MSH2 carriers.”
The lowest age at diagnosis was 26 years. However, she added, “for female carriers of an MSH6 mutation we recommend starting colonoscopies from age 30 years onwards since the cumulative risk for colorectal carcinoma was significantly lower compared with carriers of a mutation in MLH1 and MSH2 and the youngest age of diagnosis was 41 years of age.”
Dr. Hendriks, of Leiden University Medical Center, The Netherlands and colleagues came to these conclusions after studies of 146 MSH6 mutation carriers.
At 70 years of age, the cumulative risk of colorectal cancer was 69% for men and 30% for women. In addition, the cumulative risk of endometrial carcinoma was 71%.
“Based on the substantial risk of developing endometrial cancer, and the overall mortality from endometrial carcinoma of approximately 14%,” Dr. Hendriks said, “we advocate a liberal approach towards prophylactic hysterectomy, for women with a truncating MSH6 mutation, above the age of 50.”
Both microsatellite instability analysis and immunohistochemistry for the mismatch repair proteins, she added, “are very sensitive pre-screening methods for identifying families eligible for mutation analysis of the MSH6 gene.”
Source: Gastroenterology 2004;127:17-25. [ Google search on this article ]
MeSH Headings:Colonic Diseases: Colorectal Neoplasms, Hereditary Nonpolyposis: Digestive System Neoplasms: Gastrointestinal Neoplasms: Intestinal Neoplasms: Neoplasms: Neoplasms by Site: Neoplastic Syndromes, Hereditary: Colorectal Neoplasms: Base Pair Mismatch: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
