Familial pancreatic cancer—status quo
- 947 Downloads
Familial pancreatic cancer (FPC) is defined by families with at least two first-degree relatives with confirmed pancreatic ductal adenocarcinoma (PDAC) that do not fulfill the criteria of other inherited tumor syndromes with an increased risk for the development of PDAC, such as hereditary pancreatitis or hereditary breast and ovarian cancer. FPC is mostly autosomal dominant inherited and presents with a heterogeneous phenotype. Although the major gene defect has not yet been identified, some important germline mutations in the BRCA2-, PALB2-, and ATM-genes are causative in some FPC families.
It is suggested by experts to include high-risk individuals in a screening program with a multidisciplinary approach under research protocol conditions. However, neither biomarkers nor reliable imaging modalities for the detection of high-grade precursor lesions are yet available. Most screening programs are currently based on endoscopic ultrasound and magnetic resonance imaging, and first data demonstrated that precursor lesions (pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm) of PDAC can be identified. Timing and extent of surgery are still a matter of debate.
Scope of the review
The present review focuses on the clinical phenotype of FPC, its histopathological characteristics, known underlying genetic changes, genetic counseling, and screening.
KeywordsFamilial pancreatic cancer Mutation Genetics Screening PanIN IPMN Pancreatectomy
Funding for this study was through a grant of the Deutsche Krebshilfe (no. 109126) to VF, PL, and DKB.
- 3.Reimer RR, Fraumeni JF Jr, Ozols RF, Bender R (1977) Pancreatic cancer in father and son. Lancet 23:1911Google Scholar
- 11.Bartsch DK et al (2004) Prevalence of familial pancreatic cancer in Germany. Int J Cancer 20:110902–110906Google Scholar
- 17.Goldstein AM et al (1995) Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 12:333970–333974Google Scholar
- 18.Whelan AJ, Bartsch DK, Goodfellow PJ (1995) Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N Engl J Med 12:333975–333977Google Scholar
- 19.Lynch HT et al (2002) Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome. Cancer 1:9484–9496Google Scholar
- 21.Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W (2000) 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 15:87809–87811Google Scholar
- 34.Lowenfels AB, Maisonneuve P, Whitcomb DC, Lerch MM, DiMagno EP (2001) Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 11:286169–286170Google Scholar
- 77.Canto MI et al (2012) On behalf of the International CAPS Consortium International Consensus Recommendations on the management of patients with increased risk for familial pancreatic cancer (Cancer of the Pancreas Screening Consortium (CAPS) 2011 Summit). To be presented at the Digestive Disease Week (DDW), San Diego, California, USA, May 19–22Google Scholar