Low frequency of CHEK2 mutations in familial pancreatic cancer.

Familial pancreatic cancer (FPC) is a rare tumour syndrome and its underlying major gene defect is still unknown. Recently, CHEK2 has been identified as multi-organ cancer susceptibility gene associated with a predisposition to breast, prostate and colon cancer. Since these cancers also are associated with some FPC families, we have analysed 35 index patients of German FPC families for CHEK2 mutations. The CHEK2 * 1100delC mutation was found in 1 (3%) of 35 FPC families. Given the low expected mutation rate of up to 1.4% for CHEK2 * 1100delC in the European population our data are suggestive for possible contribution of CHEK2 mutations to a small subset of FPC.

Prevalence of familial pancreatic cancer in Germany.

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.