MSH6 Cancer Risk: Laura Baglietto, Noralane M. Lindor, James G. Dowty, Darren M. White, Anja Wagner, Encarna B. Gomez Garcia, Annette H. J. T. Vriends, Dutch Lynch Syndrome Study Group, Nicola R. Cartwright, Rebecca A. Barnetson, Susan M. Farrington, Albert Tenesa, Heather Hampel, Daniel Buchanan, Sven Arnold, Joanne Young, Michael D. Walsh, Jeremy Jass, Finlay Macrae, Yoland Antill, Ingrid M. Winship, Graham G. Giles, Jack Goldblatt, Susan Parry, Graeme Suthers, Barbara Leggett, Malinda Butz, Melyssa Aronson, Jenny N. Poynter, John A. Baron, Loic Le Marchand, Robert Haile, Steve Gallinger, John L. Hopper, John Potter, Albert de la Chapelle, Hans F. Vasen, Malcolm G. Dunlop, Stephen N. Thibodeau, Mark A. Jenkins Conclusion: For MSH6 mutation carriers, the estimated cumulative risks toages 70 and 80 years, respectively, were as follows: for colorectalcancer, 22% (95% confidence interval [CI] = 14% to 32%) and44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%)and 20% (95% CI = 11% to 35%) for women; for endometrial cancer,26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); andfor any cancer associated with Lynch syndrome, 24% (95% CI =16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95%CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Comparedwith incidence for the general population, MSH6 mutation carriershad an eightfold increased incidence of colorectal cancer (HR= 7.6, 95% CI = 5.4 to 10.8), which was independent of sex andage. Women who were MSH6 mutation carriers had a 26-fold increasedincidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to38.7) and a sixfold increased incidence of other cancers associatedwith Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7).
Cancer Risks Teased Out In Lynch Syndrome - French study assessed 537 families with MSH1, MSH2 and MSH6 gene mutations to determine risk by age, tumor and other factors. Conclusion: Risks were higher in families with MSH1 and MSH2 had higher risks of cancer and the risk in MSH6 was lower and cancers ordinarily orginated at a younger age
Lynch Syndrome TACSTD1 Family with Predominant Colorectal Cancer: J Clin Oncol 28:15S, 2010 Germline mutations cannot be found in MMRs MLH1 and MSH2 in about 30% of families satisfying the Amsterdam Criteria. Recently, deletions in the TACSTD1 gene have been identified as a cause of LS. Conclusion: Identification of these mutations as a cause of LS allows family members to identify their cancer risk, receive genetic counseling and obtain annual surveillance management. HT Lynch and Others; Conclusion: Identification of TACSTD1 mutations as a cause of LS has important cancer control implications for this and other LS families thereby enabling family members to identify their cancer risk, receive genetic counseling, and enroll in an appropriate cancer surveillance/management program. Extracolonic cancer risk may be decreased in TACSTD1 mutation carriers but this will require further confirmation
The Clinical Phenotype of Lynch Syndrome Due to Germline PMS2 Mutations Excellent study explaining in depth the clinical characteristics ofPMS2 mutation carriers, which has not been explored in depth up until this point. by Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center Columbus, Ohio Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington Karolinska Institute, Department of Molecular Medicine, Stockholm, Sweden Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota Department of Medical Genetics, Mayo Clinic College of Medicine, Rochester, Minnesota Queensland Institute of Medical Research, Brisbane, Queensland, AustraliaAdult Clinical Genetics, The University of Melbourne, Victoria, Australia Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Victoria, AustraliaJournal of the National Cancer Institute, 2010 102(3):193-201; doi:10.1093/jnci/djp473
Study indicates Amsterdam criteria and each of the Bethesda criteria were inadequate for identifying MSH6 mutation-carrying kindreds. MSH6 mutations may be more common than currently assumed, and the penetrance/expression of MSH6 mutations, as derived from families meeting current clinical criteria, may be misleading. To increase detection rate of MMR mutation carriers, all cancers in the Lynch syndrome tumour spectrum should be subjected to immunohistochemical analysis and/or analysis for microsatellite instability.
Study from University of Rouen, France, indicates the median age of CRC onset was 43 years, a significant difference of CRC penetrance between males and females and between MSH2 and MLH1 mutation verus MSH6 mutation carriers. Results are in agreement with published studies, which estimate cumulative CRC risk at 70 years is higher in males than females and is lower in MSH6 mutation carriers, compared to those with MSH2 and MLH1.