| ObjectiveLung cancer is one of the world’s highest morbidity and mortality of malignant tumor. Gemcitabine combined platinum is one of the standard treatment of advanced non-small cell lung cancer.The modern pharmacological genetics and genomics research shows that Cellular genetic diversity lead to the heterogeneity of tumor cells. Single nucleotide polymorphisms of encoding gene has significant correlation with curative effect,adverse reaction and prognosis, This topic combined with retrospective study and clinical follow-up data, to discuss the relationship between GSTP1、RRM1 gene polymorphism and advanced NSCLC chemotherapy(GP scheme) sensitivity. Further screening targeted and predictability predictor for NSCLC, thus, provides the basis of the molecular biology for clinical individualized chemotherapy for NSCLC.MethodsCollecting 52 cases of advanced NSCLC patients who first time to see a doctor and confirmed by pathological histology in our VIP room in 2011-2013, all cases need draw blood for extraction of leukocyte DNA before chemotherapy for the first time, use Sanger sequencing method(double DNA chain termination method) to detect gene polymorphism of GSTP1(I105V, A'G) and RRM1(C-37A、T-524C) loci. All 52 patients were accepted 2-4 cycles chemotherapy(GP scheme), the 52 patients were divided into sensitive chemotherapy group and not sensitive group. According to the follow-up study, To analyze the correlation of chemotherapy sensitivity(recent curative effect, the long-term curative effect) between GSTP1/RRM1 polymorphism and chemotherapy(GP scheme).Results1. GSTP1(I105V) has three kinds genotype:AA(61.5%)、GA(34.6%)、GG(3.8%); RRM1(C-37A) has three kinds genotype:CC(50.0%)、CA(38.5%)、AA(11.5%), RRM1(T-524C)has three kinds genotype:TT(46.2%)、TC(38.5%)、CC(15.4%), RRM1 two loci(T- 524 C, C-37 A) have nine kinds of genotype classification according to the permutation and combination.Its frequency respectively is AA/CC(5.8%)、AA/TC(5.8%)、CA/CC(5.8%)、CA/TC(32.7%)、CC/TT(46.2%)、CC/CC(3.8%)、AA/TT(0%)、CA/TT(0%)、CC/TC(0%). AA/TT、CA/TT、CC/TC these three kinds of genotypes was not checked out.2. Each genotype of GSTP1(I105V) site has no obvious correlation with the recent curative effect(P > 0.05); recent remission rate of RRM1(C-37A) loci CA genotypes is significantly higher than AA and CC genotype(P < 0.05); recent remission rate of RRM1(T-524C) loci TC genotype was significantly higher than TT and CC genotype(P < 0.05), recent remission rate of RRM1(T-524 C, C-37A) loci CA/TC genotype was significantly higher than other genotype(P<0.05)(specific genotypes for AA/CC、AA/TC、CA/CC、CC/TT、CC/CC).3. After adjusting age, gender, pathological type, clinical stage, recent remission rate of CA/TC genotype is 7.14 times as large as other genotype(P=0.008).4. Older age, late childbirth and genotype are closely related with PFS(P < 0.05). Younger, earlier stage and higher short-term curative effect is closely related with the OS(P < 0.05). Risk of disease progression of GSTP1(I105V) loci AA genotype is 1.266 times as large as AG and GG genotype(P<0.05). Risk of disease progression of all RRM1(T- 524- C, C to 37 a) loci in addition to the CA/TC genotype is 2.598 times as large as CA/TC genotype(P<0.05).5. The median PFS of GSTP1(I105V) loci AG and GG genotype is higher than AA genotype(9.9mo vs. 7.7mo, P = 0.046). The late median PFS of RRM1(T-524 C, C-37A) loci CA/TC genotype is higher than patients with other genotypes(13.7 vs. 13.7 months, P = 0.000)Conclusions1. GSTP1(I105V) and RRM1(T-524 C, C-37A) are associated with sensitivity of chemotherapy for GP scheme in patients with advanced NSCLC.2. The PFS of GSTP1(I105V) loci AG and GG genotype and RRM1(T- 524-C, C to 37 a) loci CA/TC genotype are longer.3. GSTP1(I105V) and RRM1(T-524 C, C-37A) have no significant correlation with the OS. |
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