Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: Results of an Italian multicenter study

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• 作者：Nicoletta Resta^a ; ^{nicoletta.resta@uniba.it} ; Daniela Pierannunzio^b ; Gennaro Mariano Lenato^c ; Alessandro Stella^a ; Riccardo Capocaccia^b ; Rosanna Bagnulo^a ; Patrizia Lastella^c ; Francesco Claudio Susca^a ; Cristina Bozzao^a ; Daria Carmela Loconte^a ; Carlo Sabb&agrave ; ^c ; ^d ; Emanuele Urso^e ; Paola Sala^f ; Mara Fornasarig^g ; Paola Grammatico^h ; Ada Piepoliⁱ ; Cristina Host^j ; Daniela Turchetti^k ; Alessandra Viel^l ; Luigi Memo^m ; Laura Giuntiⁿ ; Vittoria Stigliano^o ; Liliana Varesco^p ; Lucio Bertario^f ; Maurizio Genuardi^q ; ^r ; Emanuela Lucci Cordisco^s ; Maria Grazia Tibiletti^t ; Carmela Di Gregorio^u ; Angelo Andriulliⁱ ; Maurizio Ponz de Leon^v ; AIFEG 1
• 关键词：Hamartomatous polyposis ; Peutz&ndash ; Jeghers syndrome ; Surveillance protocol
• 刊名：Digestive and Liver Disease
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：45
• 期：7
• 页码：606-611
• 全文大小：585 K

文摘

Background

Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome.

Aims

To assess cancer risks in a large homogenous cohort of patients with Peutz-Jeghers syndrome, carrying, in large majority, an identified STK11/LKB1 mutation.

Methods

One-hundred and nineteen patients with Peutz-Jeghers syndrome, ascertained in sixteen different Italian centres, were enrolled in a retrospective cohort study. Relative and cumulative cancer risks and genotype-phenotype correlations were evaluated.

Results

36 malignant tumours were found in 31/119 (29 STK11/LKB1 mutation carriers) patients. The mean age at first cancer diagnosis was 41 years. The relative overall cancer risk was 15.1 with a significantly higher risk (p < 0.001) in females (22.0) than in males (8.6). Highly increased relative risks were present for gastrointestinal (126.2) and gynaecological cancers (27.7), in particular for pancreatic (139.7) and cervical cancer (55.6). The Kaplan-Meier estimates for overall cumulative cancer risks were 20 % , 43 % , 71 % , and 89 % , at age 40, 50, 60 and 65 years, respectively.

Conclusion

Peutz-Jeghers syndrome entails markedly elevated cancer risks, mainly for pancreatic and cervical cancers. This study provides a helpful reference for improving current surveillance protocols.