Familial Cancer

, Volume 13, Issue 1, pp 57–63 | Cite as

Cancer risk and genotype–phenotype correlations in PTEN hamartoma tumor syndrome

  • Marry H. NieuwenhuisEmail author
  • C. Marleen Kets
  • Maureen Murphy-Ryan
  • Helger G. Yntema
  • D. Gareth Evans
  • Chrystelle Colas
  • Pal Møller
  • Frederik J. Hes
  • Shirley V. Hodgson
  • Maran J. W. Olderode-Berends
  • Stefan Aretz
  • Karl Heinimann
  • Encarna B. Gómez García
  • Fiona Douglas
  • Allan Spigelman
  • Susanne Timshel
  • Noralane M. Lindor
  • Hans F. A. Vasen
Original Article


Patients with germline PTEN mutations are at high risk of developing benign and malignant tumours. We aimed to evaluate the cumulative risk of several types of cancer and of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease, LDD). In addition, genotype–phenotype correlations in PTEN hamartoma tumour syndrome (PHTS) were assessed. Data on patients with PTEN mutations were collected from clinical genetic centres in Western Europe, Australia, and the USA. The cumulative risk of developing cancers of the breast, thyroid, endometrium, skin, kidneys, colorectum, and lungs, and also LDD was calculated by Kaplan–Meier methods. Associations between mutations and cancer were assessed by Chi square means. A total of 180 germline PTEN mutation carriers, 81 males (45 %), from nine countries were included. The cumulative risk of developing any cancer and/or LDD at age 60 was 56 % for males and 87 % for females (p = 0.001). Females had significant higher risks of developing breast cancer, thyroid cancer, and LDD than males. The only genotype–phenotype correlation identified was a lower frequency of thyroid cancer in patients with missense mutations (p = 0.014). In conclusion, PHTS patients, particularly females, have a substantial risk of developing one or more tumours from a broad tumour spectrum. Major genotype–phenotype associations could not be identified.


PTEN phosphohydrolase Multiple hamartoma syndrome Neoplasms 


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Marry H. Nieuwenhuis
    • 1
    Email author
  • C. Marleen Kets
    • 2
  • Maureen Murphy-Ryan
    • 3
  • Helger G. Yntema
    • 2
  • D. Gareth Evans
    • 4
  • Chrystelle Colas
    • 5
  • Pal Møller
    • 6
  • Frederik J. Hes
    • 7
  • Shirley V. Hodgson
    • 8
  • Maran J. W. Olderode-Berends
    • 9
  • Stefan Aretz
    • 10
  • Karl Heinimann
    • 11
  • Encarna B. Gómez García
    • 12
  • Fiona Douglas
    • 13
  • Allan Spigelman
    • 14
    • 15
    • 16
  • Susanne Timshel
    • 17
  • Noralane M. Lindor
    • 18
  • Hans F. A. Vasen
    • 1
    • 19
  1. 1.The Netherlands Foundation for the Detection of Hereditary TumorsLeidenThe Netherlands
  2. 2.Department of Human GeneticsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Mayo Medical SchoolRochesterUSA
  4. 4.Department of Genetic MedicineSt. Mary’s HospitalManchesterUK
  5. 5.Laboratoire d’ Oncogénétique et Angiogénétique Moléculaire, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hopitaux de ParisUniversité Pierre et Marie CurieParisFrance
  6. 6.Section of Cancer Genetics, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  7. 7.Department of Clinical GeneticsLeiden University Medical CentreLeidenThe Netherlands
  8. 8.Department of Clinical Genetics, St GeorgesUniversity of LondonLondonUK
  9. 9.Department of GeneticsUniversity Medical Centre GroningenGroningenThe Netherlands
  10. 10.Institute of Human GeneticsUniversity Hospital BonnBonnGermany
  11. 11.Research Group Human Genetics, Department of Biomedicine, University Children’s HospitalUniversity of BaselBaselSwitzerland
  12. 12.Department of Clinical GeneticsUniversity Hospital MaastrichtMaastrichtThe Netherlands
  13. 13.Institute of Human GeneticsNewcastle UniversityNewcastle upon TyneUK
  14. 14.UNSW St Vincent’s Clinical SchoolSydneyAustralia
  15. 15.Hunter Family Cancer ServiceNewcastle upon TyneAustralia
  16. 16.St Vincent’s Hereditary Cancer ServiceSydneyAustralia
  17. 17.Danish HNPCC Register, Department of Gastroenterology, Hvidovre University HospitalCopenhagen UniversityCopenhagenDenmark
  18. 18.The Department of Health Science ResearchMayo ClinicScottsdaleUSA
  19. 19.Department of Gastroenterology and HepatologyLeiden University Medical CentreLeidenThe Netherlands

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