J Med Genet doi:10.1136/jmedgenet-2012-101339
  • Cancer genetics
  • Original article

High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome

  1. French Cowden Disease Network*
  1. 1Cancer Genetics Unit, Institut Bergonié, Bordeaux, France
  2. 2Inserm U 916 Institut Bergonié, Université de Bordeaux, Bordeaux, France
  3. 3Clinical and Epidemiological Research Unit, Institut Bergonié, Bordeaux, France
  4. 4Medical Genetics Unit, Centre Hospitalier Universitaire de Nantes, Nantes, France
  5. 5Department of Genetics, Hospices Civils de Lyon, Bron, France
  6. 6Medical Genetics Unit, Centre Hospitalier Universitaire de Genève, Geneve, Switzerland
  7. 7Medical Genetics Unit, Hôpital Jacques Monod, Le Havre, France
  8. 8Cancer Genetics Unit, Institut Gustave Roussy, Villejuif, France
  9. 9Medical Genetics Unit, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
  10. 10Cancer Genetics Unit, Centre Gauducheau, Nantes, France
  11. 11Cancer Genetics Unit, Centre Eugène Marquis, Rennes, France
  12. 12Cancer Genetics Unit, Centre Paul Strauss, Strasbourg, France
  13. 13Medical Genetics Unit, Centre Hospitalier Universitaire d'Angers, Angers, France
  14. 14Department of Dermatology, Hôpital Avicenne, Université Paris 13-Sorbonne Paris Cité, Bobigny, France
  1. Correspondence to Dr Michel Longy, Cancer Genetics Unit, Institut Bergonié, 229, cours de l'Argonne, Bordeaux cedex 33076, France; m.longy{at}
  • Received 9 October 2012
  • Revised 13 December 2012
  • Accepted 17 December 2012
  • Published Online First 18 January 2013


Background PTEN hamartoma tumour syndrome (PHTS) encompasses several clinical syndromes with germline mutations in the PTEN tumour suppressor gene, including Cowden syndrome which is characterised by an increased risk of breast and thyroid cancers. Because PHTS is rare, data regarding cancer risks and genotype–phenotype correlations are limited. The objective of this study was to better define cancer risks in this syndrome with respect to the type and location of PTEN mutations.

Methods 154 PHTS individuals with a deleterious germline PTEN mutation were recruited from the activity of the Institut Bergonié genetic laboratory. Detailed phenotypic information was obtained for 146 of them. Age and sex adjusted standardised incidence ratio (SIR) calculations, cumulative cancer risk estimations, and genotype–phenotype analyses were performed.

Results Elevated SIRs were found mainly for female breast cancer (39.1, 95% CI 24.8 to 58.6), thyroid cancer in women (43.2, 95% CI 19.7 to 82.1) and in men (199.5, 95% CI 106.39 to 342.03), melanoma in women (28.3, 95% CI 7.6 to 35.4) and in men (39.4, 95% CI 10.6 to 100.9), and endometrial cancer (48.7, 95% CI 9.8 to 142.3). Cumulative cancer risks at age 70 were 85% (95% CI 70% to 95%) for any cancer, 77% (95% CI 59% to 91%) for female breast cancer, and 38% (95% CI 25% to 56%) for thyroid cancer. The risk of cancer was two times greater in women with PHTS than in men with PHTS (p<0.05).

Conclusions This study shows a considerably high cumulative risk of cancer for patients with PHTS, mainly in women without clear genotype–phenotype correlation for this cancer risk. New recommendations for the management of PHTS patients are proposed.

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