GENETIC TESTING for HEREDITARY CANCER SYNDROMES Resource Guide

CANCER RISK

Published Estimates of Cancer Risks for HNPCC Mutation Carriers*

Site	Population Risk¹	MLH1/MSH2	MSH6
Colon	0.2% by age 50, 2.0% by age 70, 6% lifetime	>25% by age 50² 70-82% by age 70^2,3	10-17% by age 50⁴ Females: 30% by age 70⁴ Males: 69% by age 70⁴
Endometrium (uterine)	0.2% by age 50, 1.5% by age 70, 3% lifetime	~20% by age 50² 42-61% by age 70^2,3	13% by age 50⁴ 71% by age 70⁴
Ovary	1% by age 70 1.8% lifetime	8-fold relative risk (MSH2 only)² 12% by age 70³	Likely lower risk than MLH1/MSH2, but still increased over the general population⁴
Urinary tract (kidney and ureter)	< 1% by age 70, 1% lifetime	75-fold relative risk (MSH2 only)² 4% by age 70³	Likely lower risk than MLH1/MSH2, but still increased over the general population⁴
Small Intestine	< 1% by age 70 and lifetime	Greater than 100-fold relative risk² MLH1: 7.2% by age 70^8,9 MSH2: 4.5% by age 70⁹	Likely lower risk than MLH1/MSH2, but still increased over the general population⁴
Stomach	< 1% by age 70 and lifetime	19-fold relative risk (MSH2 only)² 13% by age 70³	Likely lower risk than MLH1/MSH2, but still increased over the general population⁴
Biliary tract	< 1% by age 70 and lifetime	2% by age 70³	Likely lower risk than MLH1/MSH2, but still increased over the general population⁴
Brain	< 1% by age 70 and lifetime	3.7% by age 70³	Likely lower risk than MLH1/MSH2, but still increased over the general population⁴
*Note: These are studies of known mutation carriers rather than individuals who meet clinical criteria for HNPCC, except where indicated otherwise.

Individuals who already have an HNPCC-associated colorectal cancer are at risk for a second HNPCC-associated cancer. Their risk for a second cancer is 30% within 10 years, or 50% within 15 years of the initial diagnosis.^5,6 This can be compared to the risk of a second colorectal cancer in the general population, which is 3% within 10 years and 5% within 15 years.⁷

Feuer EJ, Wun LM. DEVCAN: Probability of developing or dying of cancer software, version 4.0. National Cancer Institute 1999. Available at http://seer.cancer.gov/.
Vasen HFA, Vignen J, Menko FH et al. Cancer risk in families with Hereditary Nonpolyposis Colorectal Cancer diagnosed by mutation analysis. Gastroenterology. 1996;110:1020-1027.
Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81:214-218.
Hendriks YM, Wagner A, Morreau H, et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: Impact on counseling and surveillance. Gastroenterology. 2004;127:17-25.
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Mecklin J-P, Jarvinen HJ. Clinical features of colorectal carcinoma in cancer family syndrome. Dis Colon Rectum. 1986;29:160-164.
Cali RL, Pitsch RM, Thorson AG, et al. Cumulative incidence of metachronous colorectal cancer. Dis Colon Rectum. 1993;36:388-393.
Schulmann K, Brasch FE, et al. HNPCC-associated small bowel cancer: clinical and molecular characteristics. Gastroenterology. 2005 Mar;128(3):590-9.
Vasen HF, Stormorken A, et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol. 2001 Oct 15;19(20):4074-80.

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