Prevalence of familial pancreatic cancer in Germany

Abstract

Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9 -3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.

RNASEL germline variants are associated with pancreatic cancer

“…2,17 It has been suggested recently that the RNA-SEL variants Glu265X and Arg462Gln are associated with an increased risk for sporadic 13 and familial prostate cancer. 11,12,[18][19][20] Carpten et al 11 first reported a Glu265X mutation that segregated with the disease in one of the HPC1-linked prostate cancer families.…”

“…Epidemiological data suggest that dominant susceptibility genes may be responsible for about 3% of all pancreatic cancer cases. 2,3 BRCA2 germline mutations have been identified in 4.9% and 7.3% of apparently sporadic PC cases 4,5 and about 17% of and familial pancreatic cancer (FPC) cases, 6,7 respectively. There is also some evidence that mutations in CDKN2a, PRSS1, Mismatch-Repair and Fanconi anaemia genes predispose to PC, but the contribution of these genes to PC tumorigenesis is considered to be small.…”

Evaluation of the 4q32-34 Locus in European Familial Pancreatic Cancer

“…An estimated 2.7% to 10% of pancreatic cancers occur in families where there is at least one other case (5)(6)(7)(8). In some instances, this is associated with a general familial cancer syndrome, such as familial atypical multiple-mole melanoma syndrome, familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, hereditary breast-ovarian cancer syndrome, and Peutz-Jeghers syndrome (9)(10)(11)(12)(13), although in most cases, these syndromes are associated with isolated rather than multiple cases of pancreatic cancer.…”

Pancreatic Cancer Screening in a Prospective Cohort of High-Risk Patients: A Comprehensive Strategy of Imaging and Genetics

“…About 3% to 16% of pancreatic cancer is thought to be either syndromic or familial (15)(16)(17)(18)(19)(20)(21)(22), due to multiorgan cancer syndromes, other genetically driven chronic diseases, or familial groupings of pancreatic cancer with yet unidentified genetic abnormalities (familial pancreatic cancer; ref. 23).…”