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Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome.
J Natl Cancer Inst 2012; 104(18):1363-72JNCI

Abstract

BACKGROUND

Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers.

METHODS

We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan-Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period-specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population.

RESULTS

Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97).

CONCLUSION

Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.

Authors+Show Affiliations

Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, Level 3, 207 Bouverie Street, The University of Melbourne, VIC 3010, Australia.No 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, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22933731

Citation

Win, Aung Ko, et al. "Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome." Journal of the National Cancer Institute, vol. 104, no. 18, 2012, pp. 1363-72.
Win AK, Lindor NM, Young JP, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012;104(18):1363-72.
Win, A. K., Lindor, N. M., Young, J. P., Macrae, F. A., Young, G. P., Williamson, E., ... Jenkins, M. A. (2012). Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. Journal of the National Cancer Institute, 104(18), pp. 1363-72.
Win AK, et al. Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome. J Natl Cancer Inst. 2012 Sep 19;104(18):1363-72. PubMed PMID: 22933731.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. AU - Win,Aung Ko, AU - Lindor,Noralane M, AU - Young,Joanne P, AU - Macrae,Finlay A, AU - Young,Graeme P, AU - Williamson,Elizabeth, AU - Parry,Susan, AU - Goldblatt,Jack, AU - Lipton,Lara, AU - Winship,Ingrid, AU - Leggett,Barbara, AU - Tucker,Katherine M, AU - Giles,Graham G, AU - Buchanan,Daniel D, AU - Clendenning,Mark, AU - Rosty,Christophe, AU - Arnold,Julie, AU - Levine,A Joan, AU - Haile,Robert W, AU - Gallinger,Steven, AU - Le Marchand,Loïc, AU - Newcomb,Polly A, AU - Hopper,John L, AU - Jenkins,Mark A, Y1 - 2012/08/28/ PY - 2012/8/31/entrez PY - 2012/8/31/pubmed PY - 2012/12/10/medline SP - 1363 EP - 72 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 104 IS - 18 N2 - BACKGROUND: Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers. METHODS: We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan-Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period-specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population. RESULTS: Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97). CONCLUSION: Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/22933731/Risks_of_primary_extracolonic_cancers_following_colorectal_cancer_in_lynch_syndrome_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djs351 DB - PRIME DP - Unbound Medicine ER -