Follow-up, cancer risk and mortality in Peutz-Jeghers syndrome: Data from the PRED-IdF network

Peutz-Jeghers syndrome (PJS) is a very rare autosomal dominant disorder associated with an increased risk of gastrointestinal and gynecological cancers. However, risk estimates vary widely, due to the small size and retrospective nature of most studies, which may introduce recruitment bias. Accurate data are needed to improve cancer screening. The aim of this study was to estimate cancer risks in a large cohort of PJS patients. A total of 161 patients were included, half of whom were prospectively monitored as part of a surveillance network. This makes it one of the largest cohorts of PJS patients to date. We estimated age-dependent cancer risks using the Genotype Restricted Likelihood (GRL) method to correct for ascertainment bias. Standardized mortality ratios (SMRs) were calculated to assess mortality. PJS patients showed an increased risk of cancer, particularly early-onset cancers (cumulative risk before age 70: 18.1% in men, 36.8% in women). This resulted in excess mortality, especially among young women. The most frequent cancers were breast, lung, and cervical cancers. Small bowel was the site with the highest relative risk. Although the risk of pancreatic adenocarcinoma (PDAC) was elevated, it was much lower than had been reported previously (relative risk at age 50: 11.8). Degenerated intraductal papillary mucinous neoplasms (IPMN) may contribute to the risk of PDAC in PJS, while this carcinogenesis pathway accounts for only 10% of PDACs overall. We report an unexpectedly high risk of lung adenocarcinoma, calling into question the relevance of lung cancer screening in PJS.