RT Journal Article SR Electronic T1 High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 255 OP 263 DO 10.1136/jmedgenet-2012-101339 VO 50 IS 4 A1 Virginie Bubien A1 Françoise Bonnet A1 Veronique Brouste A1 Stéphanie Hoppe A1 Emmanuelle Barouk-Simonet A1 Albert David A1 Patrick Edery A1 Armand Bottani A1 Valérie Layet A1 Olivier Caron A1 Brigitte Gilbert-Dussardier A1 Capucine Delnatte A1 Catherine Dugast A1 Jean-Pierre Fricker A1 Dominique Bonneau A1 Nicolas Sevenet A1 Michel Longy A1 Frédéric Caux A1 French Cowden Disease Network YR 2013 UL http://jmg.bmj.com/content/50/4/255.abstract AB 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.