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

Abstract 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.