title: Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome.
abstract: Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. wlim@icr.ac.uk
authors.forename: W
authors.initials: W
authors.lastname: Lim
authors.forename: N
authors.initials: N
authors.lastname: Hearle
authors.forename: B
authors.initials: B
authors.lastname: Shah
authors.forename: V
authors.initials: V
authors.lastname: Murday
authors.forename: S V
authors.initials: SV
authors.lastname: Hodgson
authors.forename: A
authors.initials: A
authors.lastname: Lucassen
authors.forename: D
authors.initials: D
authors.lastname: Eccles
authors.forename: I
authors.initials: I
authors.lastname: Talbot
authors.forename: K
authors.initials: K
authors.lastname: Neale
authors.forename: A G
authors.initials: AG
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: O'Donohue
authors.forename: A
authors.initials: A
authors.lastname: Donaldson
authors.forename: R C
authors.initials: RC
authors.lastname: Macdonald
authors.forename: I D
authors.initials: ID
authors.lastname: Young
authors.forename: M H
authors.initials: MH
authors.lastname: Robinson
authors.forename: P W R
authors.initials: PW
authors.lastname: Lee
authors.forename: B J
authors.initials: BJ
authors.lastname: Stoodley
authors.forename: I
authors.initials: I
authors.lastname: Tomlinson
authors.forename: D
authors.initials: D
authors.lastname: Alderson
authors.forename: A G
authors.initials: AG
authors.lastname: Holbrook
authors.forename: S
authors.initials: S
authors.lastname: Vyas
authors.forename: E T
authors.initials: ET
authors.lastname: Swarbrick
authors.forename: A A M
authors.initials: AA
authors.lastname: Lewis
authors.forename: R K S
authors.initials: RK
authors.lastname: Phillips
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010580:Peutz-Jeghers Syndrome / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases