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Risks of less common cancers in proven mutation carriers with lynch syndrome.
J Clin Oncol. 2012 Dec 10; 30(35):4409-15.JC

Abstract

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.

Authors+Show Affiliations

University of Leipzig, Leipzig, Germany. christoph.engel@imise.uni-leipzig.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23091106

Citation

Engel, Christoph, et al. "Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 30, no. 35, 2012, pp. 4409-15.
Engel C, Loeffler M, Steinke V, et al. Risks of less common cancers in proven mutation carriers with lynch syndrome. J Clin Oncol. 2012;30(35):4409-15.
Engel, C., Loeffler, M., Steinke, V., Rahner, N., Holinski-Feder, E., Dietmaier, W., Schackert, H. K., Goergens, H., von Knebel Doeberitz, M., Goecke, T. O., Schmiegel, W., Buettner, R., Moeslein, G., Letteboer, T. G., Gómez García, E., Hes, F. J., Hoogerbrugge, N., Menko, F. H., van Os, T. A., ... Vasen, H. F. (2012). Risks of less common cancers in proven mutation carriers with lynch syndrome. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 30(35), 4409-15. https://doi.org/10.1200/JCO.2012.43.2278
Engel C, et al. Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome. J Clin Oncol. 2012 Dec 10;30(35):4409-15. PubMed PMID: 23091106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risks of less common cancers in proven mutation carriers with lynch syndrome. AU - Engel,Christoph, AU - Loeffler,Markus, AU - Steinke,Verena, AU - Rahner,Nils, AU - Holinski-Feder,Elke, AU - Dietmaier,Wolfgang, AU - Schackert,Hans K, AU - Goergens,Heike, AU - von Knebel Doeberitz,Magnus, AU - Goecke,Timm O, AU - Schmiegel,Wolff, AU - Buettner,Reinhard, AU - Moeslein,Gabriela, AU - Letteboer,Tom G W, AU - Gómez García,Encarna, AU - Hes,Frederik J, AU - Hoogerbrugge,Nicoline, AU - Menko,Fred H, AU - van Os,Theo A M, AU - Sijmons,Rolf H, AU - Wagner,Anja, AU - Kluijt,Irma, AU - Propping,Peter, AU - Vasen,Hans F A, Y1 - 2012/10/22/ PY - 2012/10/24/entrez PY - 2012/10/24/pubmed PY - 2013/5/7/medline SP - 4409 EP - 15 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 30 IS - 35 N2 - 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. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/23091106/Risks_of_less_common_cancers_in_proven_mutation_carriers_with_lynch_syndrome_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2012.43.2278?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -