title: Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study.
abstract: BACKGROUND
  Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome.
  
  
  OBJECTIVE
  To assess cancer risks in a large homogenous cohort of patients with Peutz-Jeghers syndrome, carrying, in large majority, an identified STK11/LKB1 mutation.
  
  
  METHODS
  One-hundred and nineteen patients with Peutz-Jeghers syndrome, ascertained in sixteen different Italian centres, were enrolled in a retrospective cohort study. Relative and cumulative cancer risks and genotype-phenotype correlations were evaluated.
  
  
  RESULTS
  36 malignant tumours were found in 31/119 (29 STK11/LKB1 mutation carriers) patients. The mean age at first cancer diagnosis was 41 years. The relative overall cancer risk was 15.1 with a significantly higher risk (p < 0.001) in females (22.0) than in males (8.6). Highly increased relative risks were present for gastrointestinal (126.2) and gynaecological cancers (27.7), in particular for pancreatic (139.7) and cervical cancer (55.6). The Kaplan-Meier estimates for overall cumulative cancer risks were 20%, 43%, 71%, and 89%, at age 40, 50, 60 and 65 years, respectively.
  
  
  CONCLUSIONS
  Peutz-Jeghers syndrome entails markedly elevated cancer risks, mainly for pancreatic and cervical cancers. This study provides a helpful reference for improving current surveillance protocols.
authors: Department of Biomedical Sciences and Human Oncology, Medical Genetics Unit, Aldo Moro, University of Bari, Italy. nicoletta.resta@uniba.it
authors: Nicoletta
authors: N
authors: Resta
authors: Daniela
authors: D
authors: Pierannunzio
authors: Gennaro Mariano
authors: GM
authors: Lenato
authors: Alessandro
authors: A
authors: Stella
authors: Riccardo
authors: R
authors: Capocaccia
authors: Rosanna
authors: R
authors: Bagnulo
authors: Patrizia
authors: P
authors: Lastella
authors: Francesco Claudio
authors: FC
authors: Susca
authors: Cristina
authors: C
authors: Bozzao
authors: Daria Carmela
authors: DC
authors: Loconte
authors: Carlo
authors: C
authors: Sabbà
authors: Emanuele
authors: E
authors: Urso
authors: Paola
authors: P
authors: Sala
authors: Mara
authors: M
authors: Fornasarig
authors: Paola
authors: P
authors: Grammatico
authors: Ada
authors: A
authors: Piepoli
authors: Cristina
authors: C
authors: Host
authors: Daniela
authors: D
authors: Turchetti
authors: Alessandra
authors: A
authors: Viel
authors: Luigi
authors: L
authors: Memo
authors: Laura
authors: L
authors: Giunti
authors: Vittoria
authors: V
authors: Stigliano
authors: Liliana
authors: L
authors: Varesco
authors: Lucio
authors: L
authors: Bertario
authors: Maurizio
authors: M
authors: Genuardi
authors: Emanuela
authors: E
authors: Lucci Cordisco
authors: Maria Grazia
authors: MG
authors: Tibiletti
authors: Carmela
authors: C
authors: Di Gregorio
authors: Angelo
authors: A
authors: Andriulli
authors: Maurizio
authors: M
authors: Ponz de Leon
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005833:Genital Neoplasms, Female / Q000453:epidemiology / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010580:Peutz-Jeghers Syndrome / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases