Risks of less common cancers in proven mutation carriers with lynch syndrome.


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.

PubMed ID: 23091106

Projects: GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

Publication type: Not specified

Journal: J Clin Oncol

Human Diseases: Colon cancer

Citation: J Clin Oncol. 2012 Dec 10;30(35):4409-15. doi: 10.1200/JCO.2012.43.2278. Epub 2012 Oct 22.

Date Published: 10th Dec 2012

Registered Mode: by PubMed ID

Authors: C. Engel, M. Loeffler, V. Steinke, N. Rahner, E. Holinski-Feder, W. Dietmaier, H. K. Schackert, H. Goergens, M. von Knebel Doeberitz, T. O. Goecke, W. Schmiegel, R. Buettner, G. Moeslein, T. G. Letteboer, E. Gomez Garcia, F. J. Hes, N. Hoogerbrugge, F. H. Menko, T. A. van Os, R. H. Sijmons, A. Wagner, I. Kluijt, P. Propping, H. F. Vasen

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Created: 13th May 2019 at 12:05

Last updated: 7th Dec 2021 at 17:58

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