Document Detail

Risks of less common cancers in proven mutation carriers with lynch syndrome.
MedLine Citation:
PMID:  23091106     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6.
PATIENTS AND METHODS: Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk.
RESULTS: The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers.
CONCLUSION: The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.
Christoph Engel; Markus Loeffler; Verena Steinke; Nils Rahner; Elke Holinski-Feder; Wolfgang Dietmaier; Hans K Schackert; Heike Goergens; Magnus von Knebel Doeberitz; Timm O Goecke; Wolff Schmiegel; Reinhard Buettner; Gabriela Moeslein; Tom G W Letteboer; Encarna Gómez García; Frederik J Hes; Nicoline Hoogerbrugge; Fred H Menko; Theo A M van Os; Rolf H Sijmons; Anja Wagner; Irma Kluijt; Peter Propping; Hans F A Vasen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-22
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  30     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-05-06     Revised Date:  2013-07-30    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4409-15     Citation Subset:  IM    
University of Leipzig, Leipzig, Germany.
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics
Cohort Studies
Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology*,  genetics*
DNA-Binding Proteins / genetics
Germany / epidemiology
Middle Aged
MutS Homolog 2 Protein / genetics
Neoplasms / epidemiology*,  genetics*
Netherlands / epidemiology
Nuclear Proteins / genetics
Retrospective Studies
Risk Factors
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/DNA-Binding Proteins; 0/G-T mismatch-binding protein; 0/MLH1 protein, human; 0/Nuclear Proteins; EC protein, human; EC Homolog 2 Protein
Comment In:
J Clin Oncol. 2013 Jun 10;31(17):2229-30   [PMID:  23630212 ]
J Clin Oncol. 2013 Jun 10;31(17):2230

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