Abstract
CDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of multiple cancers. Since 2000, we have run a surveillance program for CDKN2A-p16-Leiden mutation carriers. The patients are offered a yearly MRI with optionally endoscopic ultrasound. In patients with a confirmed lesion, usually, a partial resection of the pancreas is recommended. A total of 18 PDAC (8.3%) were detected in 218 mutation carriers. In this report, we describe two CDKN2A-p16-Leiden patients with a synchronous and metachronous PDAC. Including two previously-reported cases, we identified four patients with multiple PDAC: two of 18 patients within the surveillance program (11%) and two patients with a proven CDKN2A-p16-Leiden mutation not participating in the surveillance program. In conclusion, this study demonstrated a high risk of developing multiple PDAC in CDKN2A-p16-Leiden mutation carriers. After detecting a primary tumor, it is very important to exclude the presence of a second synchronous tumor. Moreover, after a partial pancreatectomy for PDAC, close surveillance is necessary. In view of the current findings, offering a total pancreatectomy might be an appropriate option in patients with an early PDAC.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Bartsch DK, Gress TM, Langer P. Familial pancreatic cancer—current knowledge. Nat Rev Gastroenterol Hepatol. 2012;9:445–53.
Zhen DB, Rabe KG, Gallinger S, Syngal S, Schwartz AG, Goggins MG, et al. BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genet Med. 2015;17:569–77.
Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000;87:809–11.
Vasen H, Ibrahim I, Ponce CG, Slater EP, Matthai E, Carrato A, et al. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers. J Clin Oncol. 2016;34:2010–9.
Potjer TP, Bartsch DK, Slater EP, Matthai E, Bonsing BA, Vasen HF. Limited resection of pancreatic cancer in high-risk patients can result in a second primary. Gut. 2015;64:1342–4.
Sibinga Mulder BG, Mieog JS, Handgraaf HJ, Farina Sarasqueta A, Vasen HF, Potjer TP, et al. Targeted next-generation sequencing of FNA-derived DNA in pancreatic cancer. J Clin Pathol. 2017;70:174–8.
Vasen HF, Wasser M, van Mil A, Tollenaar RA, Konstantinovski M, Gruis NA, et al. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology. 2011;140:850–6.
Plon SE, Eccles DM, Easton D, Foulkes WD, Genuardi M, Greenblatt MS, et al. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat. 2008;29:1282–91.
Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, et al. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut. 2011;60:950–7.
Narod SA. Bilateral breast cancers. Nat Rev Clin Oncol. 2014;11:157–66.
Roberts KJ, Blanco G, Webber J, Marudanayagam R, Sutcliffe RP, Muiesan P, et al. How severe is diabetes after total pancreatectomy? A case-matched analysis. HPB. 2014;16:814–21.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ibrahim, I., Sibinga Mulder, B.G., Bonsing, B. et al. Risk of multiple pancreatic cancers in CDKN2A-p16-Leiden mutation carriers. Eur J Hum Genet 26, 1227–1229 (2018). https://doi.org/10.1038/s41431-018-0170-y
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41431-018-0170-y
This article is cited by
-
Current status of inherited pancreatic cancer
Hereditary Cancer in Clinical Practice (2022)
-
The genetics of ductal adenocarcinoma of the pancreas in the year 2020: dramatic progress, but far to go
Modern Pathology (2020)
