title: Prospective risk of cancer and the influence of tobacco use in carriers of the p16-Leiden germline variant.
abstract: The p16-Leiden germline variant in the CDKN2A gene is associated with a high risk of melanoma and pancreatic cancer. The aims of this study were to assess the risk of developing other cancers and to determine whether tobacco use would alter cancer risk in carriers of such a variant. We therefore prospectively evaluated individuals with a p16-Leiden germline variant, participating in a pancreatic surveillance programme, for the occurrence of cancer (n=150). Tobacco use was assessed at the start of the surveillance programme. We found a significantly increased risk for melanoma (relative risk (RR) 41.3; 95% confidence interval (CI) 22.9-74.6) and pancreatic cancer (RR 80.8; 95% CI 44.7-146). In addition, increased risks were found for cancers of the lip, mouth and pharynx (RR 18.8; 95% CI 6.05-58.2) and respiratory tumours (RR 4.56; 95% CI 1.71-12.1). Current smokers developed significantly more cancers of the lip, mouth and pharynx, respiratory system and pancreas compared with former and never-smokers. In conclusion, this study shows that carriers of a p16-Leiden variant have an increased risk of developing various types of cancer, and smoking significantly increases the risk of frequently occurring cancers. Smoking cessation should be an integral part of the management of p16-Leiden variant carriers.
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Potjer
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kranenburg
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wilma
authors.initials: W
authors.lastname: Bergman
authors.affiliation: Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Wouter H
authors.initials: WH
authors.lastname: de Vos tot Nederveen Cappel
authors.affiliation: Deparment of Otorhinolaryngology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hester S
authors.initials: HS
authors.lastname: van Monsjou
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Daniela Q C M
authors.initials: DQ
authors.lastname: Barge-Schaapveld
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D016017:Odds Ratio; D064424:Tobacco Use / Q000009:adverse effects*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16