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.
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| http://dx.doi.org/10.1038/ejhg.2014.187 | DOI Listing |
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Am J Surg Pathol
September 2019
Departments of Pathology.
Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM), which is associated with an increased risk for pancreatic ductal adenocarcinoma and melanoma. CDKN2A is somatically inactivated in multiple neoplasms, raising the possibility that, although the data are not conclusive, germline CDKN2A mutation may also impose an increased risk for other neoplasms. We present a patient with a CDKN2A germline mutation (p16-Leiden mutation) and mosaicism for neurofibromatosis type 2, who presented with a small asymptomatic pancreatic lesion, detected during endoscopic ultrasound screening of the pancreas.
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Department of Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
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Eur J Hum Genet
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Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
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).
View Article and Find Full Text PDFSurveillance of second-degree relatives from melanoma families with a CDKN2A germline mutation.
Cancer Epidemiol Biomarkers Prev
October 2013
Authors' Affiliations: Department of Dermatology, Medical Statistics and Clinical Epidemiology, Clinical Genetics, Leiden University Medical Center, Leiden; Medical Affairs, Agendia, Amsterdam; Department of Pathology, VU University Medical Center, Amsterdam; The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden; and Department of Gastroenterology, Leiden University Medical Center, Leiden, the Netherlands.
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