Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome

W Lim, N Hearle, B Shah, V Murday, S V Hodgson, A Lucassen, D Eccles, I Talbot, K Neale, A G Lim, J O'Donohue, A Donaldson, R C Macdonald, I D Young, M H Robinson, P W R Lee, B J Stoodley, I Tomlinson, D Alderson, A G HolbrookS Vyas, E T Swarbrick, A A M Lewis, R K S Phillips, R S Houlston

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)308-13
Number of pages6
JournalBritish Journal of Cancer
Issue number2
Publication statusPublished - 21 Jul 2003


  • Adult
  • Aged
  • Breast Neoplasms/genetics
  • Female
  • Follow-Up Studies
  • Gastrointestinal Neoplasms/genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Peutz-Jeghers Syndrome/complications
  • Phenotype
  • Protein-Serine-Threonine Kinases/genetics
  • Risk Factors


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