ABSTRACT
OBJECTIVE: To explore the polymorphism of thymidylate synthase (TS) gene and chemosensitivity of a 5-fluorouracil (5-FU)-containing regimen in metastatic colorectal and gastric cancer. METHODS: Sixty-eight patients with metastatic gastric or colorectal cancer were included in this study. Doublets or triplets of 28 base pairs (bp) in the 5-untranslated region (UTR) of TS gene promoter were detected by polymerase chain reaction (PCR) analysis. Fragments of polymorphic products, 2R/2R, 2R/3R and 3R/3R were detected by the Agilent BioAnalyzer chip-lab system. All patients were followed up until the censoring date. A chi2 test was used to analyze the polymorphism. A Kaplan-Meier curve and a log-rank test were used to determine disease progression and overall survival. RESULTS: Among 68 patients, polymorphism expressions were 4.4% in 2R/2R, 29.4% in 2R/3R and 66.2% in 3R/3R, and clinical responses were 33.3%, 73.3% and 47.6%, respectively (2R/3R versus 3R/3R, P= 0.058). In the 64 evaluable cases, the median time to progression (TTP) was 4 months and the TTP were 3 months in 2R/2R, 6 months in 2R/3R and 4 months in 3R/3R, separately (log-rank test, P= 0.0316). Response rates to the 5-FU regimen were also better in the 2R/3R group than in the 3R/3R group both in metastatic colorectal cancer and advanced gastric cancer. CONCLUSION: Our study suggested that polymorphism of 3R/3R was more common in Chinese gastrointestinal cancer patients. Patients with a TS polymorphism expressed as 2R/3R might be more sensitive to 5-FU regimen than those with a polymorphism expressed as 3R/3R.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Fluorouracil/pharmacology , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Polymorphism, Genetic , Thymidylate Synthase/genetics , Adult , Aged , Female , Gastrointestinal Neoplasms/mortality , Genotype , Humans , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxygenase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent non-cancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorous ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.
