ERCC1Codon118Polymorphism, Protein And MRNA Expression, Clinical Outcome Of The Advanced Gastric Cancer Response To FOLFOX4Regime In Qinghai-tibetan Plateau Population

PartⅠ: ERCC1Codon118and TSER Polymorphism Expression, ClinicalOutcome of the Advanced Gastric Cancer Response to FOLFOX4Regime inQinghai-Tibetan Plateau PopulationAim: The aim of this study was to evaluate the frequency and survival benefit of theERCC1codon118C/T and TSER polymorphism in advanced gastric cancerresponse to FOLFOX4Regime in the high-altitude Qinghai-Tibetan population.Methods and Material: Polymerase chain reaction-restriction fragment lengthpolymorphism was used to determine the frequency of ERCC1118codon C/Tpolymorphism and PCR was used to determine the frequency of TSERpolymorphism in206advanced gastric cancer patients residing in thehigh-altitude Qinghai-Tibetan plateau. The correlation research ERCC1codon118C/T and TSER polymorphism,and relation to response rate and progression-free survival and overall survival with FOLFOX4chemotherapy.Results: The frequencies of the C/C, C/T, and T/T genotypes were52.4%,40.8%,and6.8%with ERCC1codon118C/T, respectively. The frequencies of the2R/2R，2R/3R and3R/3R genotypes were7.8%，31.0%and61.2%with TSER,respectively. C/C genotype of ERCC1patients had a higher response (completeand partial responses) to FOLFOX-4treatment compared with C/T and T/Tgenotype patients (47.2%vs32.6%; P=0.033).2R/2R and2R/3R genotype ofTSER patients had a higher response (complete and partial responses) toFOLFOX-4treatment compared with3R/3R genotype patients (47.5%vs31%;P=0.030). C/C with C/T and T/T polymorphism was not associated withprogression-free survival (PFS) and overall survival (OS). ERCC1and TSERpolymorphism expression was not associated.Conclusions: ERCC1C/C and TSER3R/3R genotype has high expression withgastric cancer in Qinghai-Tibetan Plateau Population. There is no relation polymorphismof ERCC1and TSER with clinical character of advanced gastric cancer. There has relation ERCC1codon118C/T polymorphism with response to FOLFOX4Regime, but no relationwith PFS and OS. PartⅡ ERCC1Protein Expression, Clinical Outcome of the Advanced GastricCancer Response to FOLFOX4Regime in Qinghai-Tibetan Plateau PopulationAim: The aim of this study was to evaluate the frequency and survival benefit of theERCC1Protein expression in a high-altitude population with advanced gastriccancer and relation with ERCC1codon118C/T polymorphism.Methods and Material: Immunohistochemical staining was used to determine theexpression of ERCC1in60advanced gastric cancer patients residing in thehigh-altitude Qinghai-Tibetan plateau. The influence of the ERCC1proteinexpression, clinicopathological features, response (RR、 PFS and OS) toFOLFOX-4chemotherapy, and follow up.Results: ERCC1protein postitive expression is35%in advanced gastric cancer.There was not associated with ERCC1protein expression and clinical character.Protein expresssion of ERCC1was no relation with FOLFOX-4treatment (RR)(P=0.057). ERCC1protein expression levels were associated with PFS(P=0.039), and OS (P=0.031).Conclusions: ERCC1protein postitive expression is lower with advanced gastriccancer in Qinghai-Tibetan Plateau. Protein expresssion of ERCC1was norelation with response of FOLFOX-4therapy (RR), but was associated withPFS and OS. PartⅢ Relation mRNA Expression of ERCC1with Clinical Outcome of theAdvanced Gastric Cancer Response to FOLFOX4Regime in Qinghai-TibetanPlateau Population Aim: The aim of this study was to evaluate the expression and survival benefit of theERCC1mRNA in a high-altitude population with advanced gastric cancer.Methods and Material: Semi-quantitative reverse transcription (RT)-PCR was usedto determine the mRNA expression of ERCC1in60advanced gastric cancerpatients residing in the high-altitude Qinghai-Tibetan plateau. The influence ofthe ERCC1mRNA expression, clinicopathological features, response(RR、PFSand OS) to FOLFOX4chemotherapy, and follow up. Analyze relation withERCC1mRNA expression and ERCC1codon118C/T polymorphism.Results: ERCC1mRNA expression is0.305in C/C genetype and0.260in C/T andT/T genetype with advanced gastric cancer. ERCC1codon118C/Tpolymorphism was not associated with ERCC1mRNA expression. HighERCC1mRNA expression levels were associated with significantly lowerFOLFOX4responses (RR, P=0.028), progression-free survival (PFS, P=0.032),and overall survival (OS, P=0.034).Conclusions: ERCC1mRNA levels may be relation with in predicting the responseand outcome of FOLFOX4therapy (RR、PFS and OS), but no relation withERCC1codon118C/T polymorphism.