title: [Hereditary predisposition to cancers of the digestive tract, breast, gynecological and gonadal: focus on the Peutz-Jeghers].
abstract: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease due to mutations in the tumor suppressor gene STK11. PJS is characterized by periorificial hyperpigmented macules (lentiginosis) and hamartomatous polyposis. Polyps can be located anywhere in the gastrointestinal tract, but are preferably observed in the small bowel (70-90%), the colon (50%) and the stomach (25%). They tend to be cancerous in a particular sequence hamartoma-dysplasia-cancer. The diagnosis is often made in the first or second decade following the appearance of lentigines or upon the occurrence of complications due to polyps (obstruction, intussusception, occult bleeding responsible for anemia). Furthermore PJS is associated with a significant increase in cancer risk (relative risk of 89% over the life according to the most recent series). Digestive cancers are the more frequent with cumulative incidences of 55% for gastro-intestinal cancer (39% for colorectal cancer, 13% for small bowel cancer and between 11 and 36% for pancreatic cancer, respectively). There is also an increased risk of non digestive cancers. In particular the risk of breast cancer is similar to that of patients carrying deleterious BRCA1 or BRCA2 mutations (cumulative incidence of 45%). Gynecological and gonadal tumors are frequent as well and can be more (adenoma malignum) or less aggressive (ovarian sex cord tumors with annular tubules and testicular tumors with calcified Sertoli cells). Finally the frequency of lung cancer is moderately increased. Recommendations for screening and management based on retrospective series in the literature have led to various strategies. The aim of this paper is to summarize the clinical and molecular diagnostic criteria of PJS as well as recommendations on screening strategies, management and monitoring.
authors.affiliation: CHRU de Lille, service de génétique clinique, hôpital Jeanne de Flandre ; service d'oncologie médicale, hôpital Claude Huriez, 2 avenue Oscar Lambret, 59000 Lille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Turpin
authors.affiliation: CHRU Lille, service de gastro-entérologie, Lille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cattan
authors.affiliation: CHRU Lille, service de biochimie et biologie moléculaire HMNO, Lille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Leclerc
authors.affiliation: CHRU Lille, service d'anatomie et cytologie pathologique, Lille, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Wacrenier
authors.affiliation: CHRU Lille, service de génétique clinique, Lille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.affiliation: CHRU Lille, service de biochimie et biologie moléculaire HMNO, Lille, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.affiliation: CHRU Lille, service de génétique clinique, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lejeune-Dumoulin
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D001943:Breast Neoplasms / Q000235:genetics*; D004067:Digestive System Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005833:Genital Neoplasms, Female / Q000235:genetics*; D006801:Humans; D007417:Intestinal Polyps / Q000175:diagnosis / Q000235:genetics; D008297:Male; D010580:Peutz-Jeghers Syndrome / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: Peutz-Jeghers syndrome; SCTATs; STK11 mutation; breast cancer; gastrointestinal cancers; hamartomatous polyposis