TITLE

CARRIERS OF LKB1 MUTATIONS IN PEUTZ-JEGHERS SYNDROME ARE AT A HIGH RISK OF CANCER

AUTHOR(S)
Lim, W.; Hearle, N.; Hodgson, S.V.; Phillips, R.K.S.; Houlston, R.S.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA91
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: Germline mutations in the LKB1 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS) a rare dominant disorder. In addition to hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with on increased risk of tumours at multiple sites. Follow up information on carriers is limited. Genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1 locus in 33 PJS families, and estimation of cancer risks in carriers and non-carriers. Methods: Thirty-three index patients with PJS were ascertained from within United Kingdom. Clinical information including details of any cancer in first- and second-degree relatives was collected on all patients. There was no selection of cases for a family history of cancer. Conformation sensitive gel electrophoresis was used for the initial screen of LKB1 mutations, followed by direct sequence analysis for mutational characterisation. Estimates of cancer risks were obtained from survival analyses and standardised mortality ratios using life table methods. Results: Germline mutations of LKB1 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1 mutations the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 was 47% (95% CI: 27 to 73%) with elevated risks of both gastrointestinal and breast cancer. Conclusion: PJS with germline mutations in LKB1 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of cancer risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1 negative cases as this group is likely to be heterogeneous.
ACCESSION #
9747900

 

Related Articles

  • Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Lim, W; Hearle, N; Shah, B; Murday, V; Hodgson, S V; Lucassen, A; Eccles, D; Talbot, I; Neale, K; Lim, A G; O'Donohue, J; Donaldson, A; Macdonald, R C; Young, I D; Robinson, M H; Lee, P W R; Stoodley, B J; Tomlinson, I; Alderson, D // British Journal of Cancer;7/21/2003, Vol. 89 Issue 2, p308 

    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...

  • Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis and Peutz-Jeghers syndrome. Dunlop, M.G. // Gut;Oct2002 Supplement 5, Vol. 51 Issue 4, pV21 

    Provides guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, juvenile polyposis and Peutz-Jeghers syndrome. Clinical surveillance and management of the gastrointestinal tract; Awareness of risks and malignancies of the...

  • Tumour Suppressors: Mystery molecule. Novak, Kristine // Nature Reviews Cancer;Oct2002, Vol. 2 Issue 10, p719 

    Reports that germ-line mutations in LKB1 genes are associated with Peutz-Jeghers syndrome (PJS), a disorder characterized by a predisposition to gastrointestinal polyopsis and cancer. Mouse model showing the pathogenesis of JPS; Role of the loss of LKB1 in normal cells in the formation of...

  • A role for LKB1 gene in human cancer beyond the Peutz—Jeghers syndrome. Sanchez-Cespedes, M. // Oncogene;12/13/2007, Vol. 26 Issue 57, p7825 

    Germline LKB1 mutations are responsible for Peutz–Jeghers syndrome (PJS). Tumors at several locations frequently arise in these patients, confirming that LKB1 is linked to cancer predisposition and is therefore a bona fide tumor-suppressor gene. In humans, the LKB1 gene is located in the...

  • Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. Olschwang, Sylviane; Boisson, Cécile; Thomas, Gilles // Journal of Medical Genetics;Jun2001, Vol. 38 Issue 6, p356 

    Introduction--Germline mutations of the STK11/LKB1 tumour suppressor gene (19p13.3) are responsible for Peutz-Jeghers syndrome (PJS), a rare genetic disorder, which is dominantly inherited. In addition to the typical hamartomatous gastrointestinal polyps and perioral pigmented lesions, PJS is...

  • STRAD in Peutz-Jeghers syndrome and sporadic cancers. de Leng, W. W. J.; Keller, J. J.; Luiten, S.; Musler, A. R.; Jansen, M.; Baas, A. F.; de Rooij, F. W. M.; Gille, J. J. P.; Menko, F. H.; Offerhaus, G. J. A.; Weterman, M. A. J. // Journal of Clinical Pathology;Oct2005, Vol. 58 Issue 10, p1091 

    Background/Aims: LKB1 is a tumour suppressor gene that is associated with Peutz-Jeghers syndrome (PJS), a rare autosomal dominant cancer predisposition syndrome. However, germline mutations in the LKB1 gene are found in only about 60% of patients with PJS, suggesting the existence of a second...

  • Duodenal cancer in a patient with Peutz-Jeghers syndrome: molecular analysis. Nakamura, Toshio; Suzuki, Shohachi; Yokoi, Yoshihiro; Kashiwabara, Hidefumi; Maruyama, Keiji; Baba, Satoshi; Nakagawa, Hidewaki; Nakamura, Satoshi // Journal of Gastroenterology;2002, Vol. 37 Issue 5, p376 

    We experienced an unusual case of duodenal adenocarcinoma associated with Peutz-Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on the presence of mucocutaneous pigmentation of the lip...

  • Multifocal Jejuno-ileal carcinoma in a 7-year-old boy with Peutz-Jeghers syndrome: A rare occurence. Ranjan, Richa; Nath, Devajit; Dey, Santosh; Arava, Sudheer // Indian Journal of Medical & Paediatric Oncology;Jan-Mar2014, Vol. 35 Issue 1, p121 

    A letter to the editor is presented regarding the case of multifocal jejuno-ileal carcinoma in a 7-year-old boy with Peutz-Jeghers syndrome (PJS).

  • Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1. Gaude, H; Aznar, N; Delay, A; Bres, A; Buchet-Poyau, K; Caillat, C; Vigouroux, A; Rogon, C; Woods, A; Vanacker, J-M; Höhfeld, J; Perret, C; Meyer, P; Billaud, M; Forcet, C // Oncogene;3/22/2012, Vol. 31 Issue 12, p1582 

    LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a serine/threonine kinase that associates with the pseudokinase...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics