title: High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome.
abstract: 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.
authors: Cancer Genetics Unit, Institut Bergonié, 229, cours de l'Argonne, Bordeaux cedex 33076, France.
authors: Virginie
authors: V
authors: Bubien
authors: Françoise
authors: F
authors: Bonnet
authors: Veronique
authors: V
authors: Brouste
authors: Stéphanie
authors: S
authors: Hoppe
authors: Emmanuelle
authors: E
authors: Barouk-Simonet
authors: Albert
authors: A
authors: David
authors: Patrick
authors: P
authors: Edery
authors: Armand
authors: A
authors: Bottani
authors: Valérie
authors: V
authors: Layet
authors: Olivier
authors: O
authors: Caron
authors: Brigitte
authors: B
authors: Gilbert-Dussardier
authors: Capucine
authors: C
authors: Delnatte
authors: Catherine
authors: C
authors: Dugast
authors: Jean-Pierre
authors: JP
authors: Fricker
authors: Dominique
authors: D
authors: Bonneau
authors: Nicolas
authors: N
authors: Sevenet
authors: Michel
authors: M
authors: Longy
authors: Frédéric
authors: F
authors: Caux
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human