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Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome

Authors' Affiliations: ¹ Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom; ² Institute of Human Genetics, Heinrich-Heine University, Düsseldorf, Germany; ³ Department of Clinical Genetics and Human Genetics, VU University Medical Centre; ⁴ Department of Pathology, Academic Medical Centre, Amsterdam, the Netherlands, ⁵ Institut Paoli-Calmettes, Institut National de la Sante et de la Recherche Medicale UMR 599, Marseilles, France; ⁶ Division of Gastroenterology, Department of Internal Medicine, Mayo Clinic, Mayo Foundation, Rochester, Minnesota; ⁷ Department of Internal Medicine, Erasmus MC University Medical Centre, Rotterdam, the Netherlands; ⁸ Discipline of Medical Genetics, Faculty of Health, Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia; ⁹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; ¹⁰ Division of Molecular Medicine and Genetics, University of Michigan, Ann Arbor, Michigan; ¹¹ Department of General and Visceral Surgery, St. Josefs-Hospital Bochum-Linden, Bochum, Germany; ¹² Department of General, Visceral and Thoracic Surgery, Klinken Maria Hilf, Mönchengladbach, Germany; ¹³ Polyposis Registry, St. Mark's Hospital, Harrow, United Kingdom; and ¹⁴ Professorial Surgical Unit, Faculty of Medicine, St. Vincent's Hospital Clinical School, University of New South Wales; Hunter Family Cancer Service and New South Wales and Australian Capital Territory Hereditary Cancer Registries, Sydney, New South Wales, Australia

Requests for reprints: Richard S. Houlston, Section of Cancer Genetics, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom. Phone: 44-20-8722-4175; Fax: 44-20-8722-4359; E-mail: Richard.Houlston{at}icr.ac.uk.

Background: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited.

Experimental Design: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations.

Results: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference ² = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk.

Conclusions: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

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