Originally published as JCO Early Release 10.1200/JCO.2009.23.7784 on August 31 2009

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Ten Years After Mutation Testing for Lynch Syndrome: Cancer Incidence and Outcome in Mutation-Positive and Mutation-Negative Family Members

From the Departments of Surgery and Medical Genetics, University of Helsinki, Helsinki; and Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.

Corresponding author: Heikki J. Järvinen, MD, PhD, Department of Surgery, PO Box 340, FI-00029 HUS, Helsinki, Finland; e-mail: Heikki.Jarvinen{at}hus.fi.

Purpose Colonoscopies with polypectomies and endometrial biopsies with transvaginal ultrasonography, repeated at 2- to 3-year intervals, are performed for prevention or early detection of cancer in patients with DNA mismatch repair gene mutation causing Lynch syndrome. The long-term effectiveness of surveillance was evaluated in Lynch syndrome family members tested approximately 10 years ago.

Materials and Methods Cancer incidence and survival were determined after an 11.5-year follow-up in 242 mutation-positive and 367 mutation-negative participants. These participants in 57 Lynch syndrome families with 14 different mutations were at 50% risk. The median age was 36 years (range, 18 to 72 years) in mutation carriers and 42 years (range, 18 to 72 years) in mutation-negative participants, and none had had cancer of the Lynch syndrome type.

Results Compliance was 95.9% for the colonic surveillance and 97.1% for the gynecologic surveillance. Colorectal cancer (CRC) occurred in 30 mutation-positive participants, and 74 participants had adenomas removed. Three patients died of CRC. Endometrial cancer (EC) occurred in 19 of 103 women at risk, and 48 women had prophylactic hysterectomy. Six of 112 women at risk had ovarian cancer. The overall cancer risk ratio (RR) in mutation carriers was 5.80 (95% CI, 3.4 to 9.5). Cancer mortality rate (RR = 2.28; 95% CI, 0.82 to 6.31) and overall death rate (RR = 1.26; 95% CI, 0.65 to 2.46) were not significantly increased.

Conclusion Long-term compliance in surveillance for CRC and EC exceeded 95% in Lynch syndrome. All CRC deaths were not prevented as a result of noncompliance or missed lesions. Still, after 10 years of surveillance, no significant increase in mortality had occurred compared with mutation-negative relatives.

Supported by the Helsinki University Hospital Research Fund.

Presented at the 3rd Biennial Meeting of the International Society for Gastrointestinal Hereditary Tumours, June 24-27, 2009, Düsseldorf, Germany.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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