Faculty Collaboration Database

Polymorphisms of p16, p27, p73, and MDM2 modulate response and survival of pancreatic cancer patients treated with preoperative chemoradiation. Ann Surg Oncol 2009 Feb;16(2):431-9

Date

11/21/2008

Pubmed ID

19020940

DOI

10.1245/s10434-008-0220-8

Scopus ID

2-s2.0-59449096031 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

Genetic polymorphisms play an important role in clinical response to cytotoxic therapies. We hypothesized that polymorphisms in cell cycle genes may modulate response to preoperative chemoradiation and survival of pancreatic cancer patients. We evaluated 12 single-nucleotide polymorphisms (SNPs) of ten cell cycle genes in 88 patients with resectable adenocarcinoma of the pancreatic head who were treated with neoadjuvant concurrent gemcitabine and radiotherapy. Response was assessed by computerized tomography obtained before and 4-6 weeks after preoperative treatment. Time to tumor progression and survival after treatment were measured. Patients underwent pancreaticoduodenectomy (PD) if no disease progression was found at restaging after preoperative therapy. MDM2 T309G and p16 C580T genotype distributions were significantly different in the patients who underwent PD and those who did not (P = 0.025 for MDM2; P = 0.016 for p16). The MDM2 and p27 genotypes had a significant effect on survival times after treatment (log-rank test, P = 0.010 and P = 0.050, respectively). A strong joint effect of these two genes was observed (log-rank test, P = 0.010). The p73 and p16 polymorphic genotypes were significantly associated with shorter time to tumor progression (log-rank test, P = 0.021 and P = 0.039, respectively). A gene-dosage effect on time to tumor progression was observed for polymorphisms in the p73, p16, and MDM2 genes. The hazard ratios for patients with one, two, or three adverse genotypes were 2.13 (1.04-4.36), 3.18 (1.37-7.39), and 10.09 (3.17-32.05), respectively. These findings suggest these polymorphisms in the cell cycle genes are promising prognostic markers for patients with pancreatic cancer.

Author List

Chen J, Li D, Killary AM, Sen S, Amos CI, Evans DB, Abbruzzese JL, Frazier ML

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Pancreatic Ductal
Chemotherapy, Adjuvant
Cisplatin
Combined Modality Therapy
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p27
DNA-Binding Proteins
Deoxycytidine
Disease Progression
Female
Humans
Male
Middle Aged
Neoadjuvant Therapy
Neoplasm Proteins
Nuclear Proteins
Pancreatic Neoplasms
Pancreaticoduodenectomy
Polymorphism, Single Nucleotide
Prognosis
Proto-Oncogene Proteins c-mdm2
Radiotherapy, Adjuvant
Survival Rate
Time Factors
Tumor Protein p73
Tumor Suppressor Proteins