Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).
We found that the TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.
These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.
We found that the combination of AZD7762 and olaparib produced significant radiosensitization in p53 mutant pancreatic cancer cells and in all of the isogenic cancer cell lines.
Using the whole-cell recording mode of the patch-clamp technique, functional ion channels were electrophysiologically characterized in PANC-1 (K-ras G12D (+/-), p53R273C, Deltap16), BxPC-3 (smad4-, p53 Y220C, Deltap16), and MiaPaCa-2 [transforming growth factor-beta receptor type II defect, K-ras G12C(-/-), p53R248W, Deltap16] human pancreatic cancer cell lines.
We determined the frequency of p53 protein overexpression and p53 point mutations in the conserved and nonconserved domains in pancreatic cancers as well as the coincidence of Ki-ras mutation in pancreatic ductal adenocarcinoma.
Unexpectedly, these drugs did not suppress the growth of BRCA2-deficient pancreatic cancer cell lines from humans or gene-targeted mice expressing active Kras and trans-dominant inhibitory mutant Trp53.
K-ras<sup>LSL-G12D/+</sup>:: p53<sup>LSL-R172H/+</sup>:: Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer that specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre.
Thus, our results provide functional evidence that the deletion or mutational inactivation of the p53 gene represents an important step in the tumorigenicity of pancreatic cancer.
Based on these findings, trichodermin is a potential therapeutic agent worthy of further development into a clinical trial candidate for treating cancer, especially the mutant p53pancreatic cancer.
Accumulating evidence strongly suggests that p53 mutations contribute to the acquisition and/or maintenance of drug-resistant property of pancreatic cancer.
The methylation status of Reprimo CpG island was analyzed by methylation-specific polymerase chain reaction in a large series of pancreatic cancers and was correlated with p53 mutation status, genetic instability (as measured by the fractional allelic loss), and clinicopathologic features.
Overexpression of Gli1, MDM2 and mutant p53 contributes to the development and progression of PC, and plays an important role in predicting PC patients' prognosis.
This meta-analysis suggests that Pro allele in P53Arg72Pro is significantly associated with the increased risks of digestive tract cancers, especially for Asians, and for gastric cancer, colorectal cancer and gallbladder and pancreatic cancer.
Although the rate of p53 mutations in pancreatic tumours is of the same order as in other adenocarcinomas (> or = 50%), an antibody response was found in only 5/78 (6.4%) sera from patients with pancreatic cancer.
Despite several potential advantages of stool testing for pancreatic cancer and its biological plausibility, only six studies investigating two genetic markers in stool (the K-ras and the p53 gene) could be identified.
We found that six novel tagging single-nucleotide polymorphisms (SNPs) (i.e, MAP2 rs35075084 T > deletion, PRKAG2 rs2727572 C > T and rs34852782 A > deletion, TP53rs9895829 A > G, and RPTOR rs62068300 G > A and rs3751936 G > C) were significantly associated with an increased PanC risk.