TY - JOUR T1 - High cumulative risks of cancer in patients with <em>PTEN</em> hamartoma tumour syndrome JF - Journal of Medical Genetics JO - J Med Genet SP - 255 LP - 263 DO - 10.1136/jmedgenet-2012-101339 VL - 50 IS - 4 AU - Virginie Bubien AU - Françoise Bonnet AU - Veronique Brouste AU - Stéphanie Hoppe AU - Emmanuelle Barouk-Simonet AU - Albert David AU - Patrick Edery AU - Armand Bottani AU - Valérie Layet AU - Olivier Caron AU - Brigitte Gilbert-Dussardier AU - Capucine Delnatte AU - Catherine Dugast AU - Jean-Pierre Fricker AU - Dominique Bonneau AU - Nicolas Sevenet AU - Michel Longy AU - Frédéric Caux AU - French Cowden Disease Network Y1 - 2013/04/01 UR - http://jmg.bmj.com/content/50/4/255.abstract N2 - 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&lt;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. ER -