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Cancer risks in LKB1 germline mutation carriers
  1. H Mehenni1,
  2. N Resta2,
  3. J-G Park3,
  4. M Miyaki4,
  5. G Guanti2,
  6. M C Costanza5
  1. 1Unité de Gastroentérologie et Hépatologie, Centre Médico-Chirurgical de Plainpalais et Département de Biologie Cellulaire, Université de Genève, Switzerland
  2. 2Sezione di Genetica Medica Dip di Biomedicina dell’Età Evolutiva, Università di Bari, Italy
  3. 3Laboratory of Cell Biology, Cancer Research Centre, and Cancer Research Institute, Seoul National University College of Medicine, Korea
  4. 4Hereditary Tumour Research Project, Tokyo Metropolitan Komagome Hospital, Japan
  5. 5Division of Clinical Epidemiology, Geneva University Hospital, Switzerland
  1. Correspondence to:
    Dr H Mehenni
    Unité de Gastroentérologie et Hépatologie, Centre Médico-chirurgical de Plainpalais, 17–19 rue de Carouge, 1205-Genève, Switzerland; mehenni{at}


Background and aims: Germline mutations in the LKB1 gene are known to cause Peutz-Jeghers syndrome, which is an autosomal dominant disorder characterised by hamartomatous polyposis and mucocutaneous pigmentation. This syndrome is associated with an increased risk of malignancies in different organs but there is a lack of data on cancer range and risk in LKB1 germline mutation carriers.

Patients and methods: The cumulative incidence of cancer in 149 Peutz-Jeghers syndrome patients with germline mutation(s) in LKB1 was estimated using Kaplan-Meier time to cancer onset analyses and compared between relevant subgroups with log rank tests.

Results: Thirty two cancers were found in LKB1 mutation carriers. Overall cancer risks at ages 30, 40, 50, 60, and 70 years were 6%, 18%, 31%, 41%, and 67%, respectively. There were similar overall cancer risks between male and female carriers. However, there were overall cancer risk differences for exon 6 mutation carriers versus non-exon 6 mutation carriers (log rank p = 0.022 overall, 0.56 in males, 0.0000084 in females). Most (22/32) of the cancers occurred in the gastrointestinal tract, and the overall gastrointestinal cancer risks at ages 40, 50, 60, and 70 years were 12%, 24%, 34%, and 63%, respectively. In females, the risks for developing gynaecologic cancer at ages 40 and 50 years were 13% and 18%, respectively.

Conclusions: Mutations in exon 6 of LKB1 are associated with a higher cancer risk than mutations within other regions of the gene. Moreover, this study provides age related cumulative risks of developing cancer in LKB1 mutation carriers that should be useful for developing a tailor made cancer surveillance protocol for Peutz-Jeghers syndrome patients.

  • Peutz-Jeghers syndrome
  • cumulative cancer risk
  • LKB1 gene mutations
  • surveillance
  • exon specific risk

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  • Published online first 11 January 2006

  • Conflict of interest: None declared.

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