Patterns of genetic alterations in pancreatic cancer: A pooled analysis

Abstract

Both K‐ras and p53 gene mutations are found commonly in pancreatic tumors. Analysis of the mutational patterns may provide insight into disease etiology. To further describe the mutational patterns of pancreatic cancer and to assess the evidence to date, we performed a pooled analysis of the published data on genetic mutations associated with pancreatic ductal adenocarcinoma. We included data from studies that evaluated point mutations in the two genes most studied in pancreatic cancer, K‐ras and p53. A majority of the 204 tumors had mutations in at least one gene, with 29% having both K‐ras and p53 mutations, 39% with K‐ras mutation alone, and 16% having p53 mutation alone. Sixteen percent of tumors lacked mutation in either gene. K‐ras mutations were present in high frequencies in all tumor grades (>69%). A statistically significant trend was observed for p53 mutation with higher tumor grade (P = 0.04). For K‐ras, G2 and G3 grades, combined, had notably higher prevalences of mutation than G1 (P = 0.004). CGT mutations in K‐ras codon 12 were marginally associated with lower tumor grade (P for trend = 0.09), and these tumors were somewhat less likely to have a p53 mutation than tumors with other K‐ras mutations (P = 0.06). In the 59 K‐ras+/p53+ tumors, 64% had the same type of mutation (transition or transversion) in both genes, suggesting a common mechanism. The mutational pattern of p53 in pancreatic cancer is similar to bladder cancer, another smoking‐related cancer, but not to lung cancer. Analyses of molecular data, such as that performed here, present new avenues for epidemiologists in the study of the etiology of specific cancers. Environ. Mol. Mutagen. 33:111–122, 1999 © 1999 Wiley‐Liss, Inc.

Differing molecular pathology of pancreatic adenocarcinoma in Egyptian and United States patients

“…About one‐quarter (24.2%) of tumors from Egyptian patients and 36.7% of tumors from US patients included in this study had both K‐ras and p53 mutations, which was similar to previous studies 32, 41, 42. Blanck et al 42 reported 64% of pancreatic cancer patients with both K‐ras and p53 mutations had the same type of mutation (transition or transversion), which suggested an environmental agent might have acted on both genes in a similar manner, or that the particular DNA base is prone to mutation 42…”

A Population-Based, Case-Control Study of Polymorphisms in Carcinogen-Metabolizing Genes, Smoking, and Pancreatic Adenocarcinoma Risk

“…Moreover, the lack of interaction between smoking and CYP1A1 polymorphisms in this study also suggests that the major mechanism by which smoking increases the risk of pancreatic cancer is not through the direct action of tobacco-associated constituents (e.g., PAH) that are modified by CYP1A1. Further, evidence for a direct effect of smoking on pancreatic cancer risk is not supported by the spectra of p53 and K-ras mutations that are commonly observed in exocrine pancreatic adenocarcinoma (57,58).…”

“…The spectrum of p53 mutations in pancreatic adenocarcinoma is mixed in that the number and predominance of transversions of the p53 gene are more similar to those associated with bladder cancer and colorectal cancer than with smoking-related cancers of the lung, head and neck, and esophagus (57,58). In addition, at least 75% of pancreatic tumors show mutations in codon 12 of the K-ras oncogene.…”

19-nor-1α,25-Dihydroxyvitamin D2(Paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo

“…34 Therefore, we also used the AsPC-cell line which harbors a Ki-Ras mutation and has previously been shown to be growth inhibited by ,25(OH) 2 D 3 . 35,36 As shown in Figure 3A, AsPC-cells treated with increasing doses of paricalcitol and ,25(OH) 2 D 3 . were growthinhibited to comparable levels, demonstrating that Ki-Ras mutations do not inhibit the antiproliferative effects of paricalcitol.…”