Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome
N Hearle,Valérie Schumacher,Fred H. Menko,Sylviane Olschwang,Lisa A. Boardman,Johan J.P. Gille,J J Keller,Anne Marie Westerman,Rodney J. Scott,Wendy Lim,Jill D. Trimbath,Francis M. Giardiello,Stephen B. Gruber,G. Johan A. Offerhaus,Felix W. M. de Rooij,J. H. Paul Wilson,Anika Hansmann,Gabriela Möslein,Brigitte Royer-Pokora,Tilman Vogel,Robin K. S. Phillips,Allan D. Spigelman,Richard S. Houlston +22 more
TLDR
Cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference χ2; 1 df; P = 0.43), and the type or site of STK 11/L KB1 mutation did not significantly influence cancer risk.Abstract:
BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.read more
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ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Sapna Syngal,Randall E. Brand,James M. Church,Francis M. Giardiello,Heather Hampel,Randall W. Burt +5 more
TL;DR: Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
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Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)
Stuart Cairns,John H. Scholefield,Robert Steele,Malcolm G. Dunlop,Huw Thomas,Gareth Evans,Jayne Eaden,Matthew D. Rutter,Wendy P Atkin,Brian P. Saunders,Anneke Lucassen,Paul Jenkins,Peter D. Fairclough,Christopher R J Woodhouse,Ireland +14 more
TL;DR: Advice on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer and for those with inflammatory bowel disease is provided.
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Tumor suppressors and cell metabolism: a recipe for cancer growth
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LKB1 modulates lung cancer differentiation and metastasis
Hongbin Ji,Matthew R. Ramsey,D. Neil Hayes,Cheng Fan,Kate McNamara,Piotr Kozlowski,Chad Torrice,Michael C. Wu,Takeshi Shimamura,Samanthi A. Perera,Mei-Chih Liang,Dongpo Cai,George N. Naumov,Lei Bao,Cristina Contreras,Danan Li,Liang Chen,Janakiraman Krishnamurthy,Jussi Koivunen,Lucian R. Chirieac,Robert F. Padera,Roderick T. Bronson,Neal I. Lindeman,David C. Christiani,Xihong Lin,Geoffrey I. Shapiro,Pasi A. Jänne,Bruce E. Johnson,Matthew Meyerson,David J. Kwiatkowski,Diego H. Castrillon,Nabeel Bardeesy,Norman E. Sharpless,Kwok-Kin Wong +33 more
TL;DR: LKB1 is established as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis in lung cancer, and expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes as targets of LKB1 repression.
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AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo
Brandon Faubert,Gino Boily,Said Izreig,Takla Griss,Bozena Samborska,Zhifeng Dong,Fanny Dupuy,Christopher Chambers,Benjamin J. Fuerth,Benoit Viollet,Benoit Viollet,Benoit Viollet,Orval A. Mamer,Daina Avizonis,Ralph J. DeBerardinis,Peter M. Siegel,Russell G. Jones +16 more
TL;DR: It is shown that AMPK negatively regulates aerobic glycolysis (the Warburg effect) in cancer cells and suppresses tumor growth in vivo, and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation.
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A serine/threonine kinase gene defective in Peutz–Jeghers syndrome
Akseli Hemminki,David Markie,Ian Tomlinson,Egle Avizienyte,Stina Roth,Anu Loukola,Graham R. Bignell,William H. Warren,Maria Aminoff,Pia Höglund,H Järvinen,Paula Kristo,Katarina Pelin,Maaret Ridanpää,Reijo Salovaara,T Toro,Walter F. Bodmer,S Olschwang,Anne S. Olsen,Michael R. Stratton,A de la Chapelle,Lauri A. Aaltonen +21 more
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