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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 publication

DOI

10.1038/sj.bjc.6601030

Type

Journal article

Journal

Br J Cancer

Publication Date

21/07/2003

Volume

89

Pages

308 - 313

Keywords

AMP-Activated Protein Kinase Kinases, Adult, Aged, Breast Neoplasms, Female, Follow-Up Studies, Gastrointestinal Neoplasms, Genetic Predisposition to Disease, Genotype, Germ-Line Mutation, Humans, Male, Middle Aged, Peutz-Jeghers Syndrome, Phenotype, Protein Serine-Threonine Kinases, Risk Factors