Further Observations on LKB1/STK11 Status and Cancer Risk in Peutz-Jeghers Syndrome

Br J Cancer. 2003 Jul 21;89(2):308-13. doi: 10.1038/sj.bjc.6601030.

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.

MeSH terms

  • 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*
  • Peutz-Jeghers Syndrome / genetics*
  • Phenotype
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk Factors

Substances

  • STK11 protein, human
  • Protein-Serine-Threonine Kinases