A Preliminary Research About Genetic Polymorphisms Of GSTs And Clinical Characteristics And Response To Chemotherapy Of Non-hodgkin’s Lymphoma(NHL)

Objective：To investigate the relationship between the single nucleotide polymorphism ofGSTP1 and GSTM1 and the clinical characteristics , response to chemotherapy and hematologictoxicity in patients with non-Hodgkin’s lymphomas(NHL)．Methods: A total of 72 patients with NHL who were diagnosed accordillg to WHO classificationand confirmed by pathology and IHC between July 2009 and October 2011 at twohospitals(shanxi Provincial Tumor Hospital and Datong third people’s hospital)were included inour study. Clinical stages were identified by The Ann Arbor staging System.All of the patientswere treated with CHOP or CHOP-based chemotherapy.The reponses were scored according toInternational Working Group Criteria for NHL.Hematologic toxicity were evaluated accordingacute and subacute toxicity criteria of chemotherapy drugs.Peripheral blood samples wereobtained before the therapy. The single nucleotide polymorphism of GSTP1 and GSTM weredetected using PCR-LDR method．Data was analysed by SPSS 13.0 package.when P<0．05，itwas statistically significance．Based on unconditional logistic regression analysis,the associationbetween different genetypes and the clinical characteristics，the response of chemotherapy andhematologic toxicity were analyzed by comparing odds ratio(OR)with 95％confidenceinterval(CI)．Results: 1、Of the 72 NHL patients，the genotypic frequencies of the GSTP1 AA，GA and GGwere 68.8%，33.3%, 2.8 %, respectively , while the genotypic frequencies of GSTM1 present andGSTM1 null were all 50%.2、No significant differences was found between the distribution of GSTP1 genotypicfrequencies and groups categorization according to gender，age，Source of cells, B symptoms,Ann Arbor stage, Extranodal involvement , Elevated LDH, IPI score ( P > 0.05 ). GSTM1nullgenotype was higher in T-cell type patients than in B-cell type patients(72.7％VS 40％)，whileGSTM1 present genotype was lower in T-cell patients than in B-cell patients(27.3％VS60％)，with statistical significance(P=0.011,OR=4.0,95%CI,1.337-11.965)；GSTM1null genotype waslower in LDH rise group than in LDH normal group (35.3％VS 63.2％)，while GSTM1 presentgenotype was higher in LDH rise group than in LDH normal group (64.7％VS36.8％)，withstatistical significance（P=0.018,OR=0.318,95%CI 0.121-0.834) . 3、Of the 72 NHL patients ,total response rate of chemotherapy was 77.8% ,including 40 patientswith complete response,16 with partial response, 4 with stable disease,12 with progressivedisease.The response rate to chemotherapy in patients with AA and GA/GG genotypes in the 105GSTP1 codons were 76.1%，80.8%，no significant difference was abserved（χ2=6.209，P=0.646）；The response rate to chemotherapy in patients with GSTM1 present and GSTM1nullgenotypes were 72.2%、83.3%，no significant difference was abserved（χ2=1.286,P=0.257）.4、The incidences of grade III- IV thrombocytopemia in patients with AA and GA/GG genotypesin the 105 GSTP1 codons were 8.7%、30.8%，respectively,with statistical significance (P=0.037,OR=4.667, 95%CI,1.245-17.489); There was no significant differences of grade III- IVleukocytopenia,anemia,thrombocytopemia among patients with GSTM1null genotype comparedto those with GSTM1 present genotype(P were 0.151, 1.00, 0.206).Conclusion:1.T-cells lymphoma may be asscociated with GSTM1null.2.GSTM1null may be asscociated with low LDH level.3.The GSTP1105 GA/GG genotypes were associated with severe grade III-IVthrombocytopemia.4、There were no associations between GSTM1 and GSTP1105 gene Polymorphisms and clinicalresponse to threapy，GSTM1 polymorphisms may not be an genetic indicator of the sensitivityof CHOP or CHOP-based chemotherapy.