Polymorphisms of GSTs in Lung Adenocarcinoma Patients Followed in the Context of a Biobank

Abstract

Background : Lung Adenocarcinoma (ADC) has been recently associated with distinct molecular changes, leading to the development of molecular-based targeted therapy. The Nancy’s Centre of Biological Resources (“Centre des Ressources Biologiques”, CRB) is an ISO 9001-2000 certified biobank with biological material and follow-up data from lung cancer patients, which collected during the last 20 years. Objective : To estimate and compare the frequency of Glutathionne S -Transferase (GST) polymorphisms in a French population of ADC patients. Methods : A retrospective study was conducted by the CRB between 1988 and 2007: 296 consecutive patients operated upon for ADC and 447 healthy subjects were evaluated. Genomic DNA was obtained from peripheral blood samples collected in EDTA tubes. The DNA was extracted using proteinase K digestion and phenol: chloroform purification. The GST polymorphisms were studied with duplex SYBR Green q PCR using specific primers and results being read on melt curves. Results : Two GST classes were monitored during this research. The Mu class GST (GSTM) and the Theta class GST (GSTT) members. We studied the incidence of each genotype, as well as the GSTMT (combined Mu and Theta class) and null genotype in ADC and control patients. ADC patients had a higher incidence of the GSTM polymorphism (p < 0.0001, 95%CI 1.63 - 3.24) and a lower incidence of the GSTT polymorphism (p < 0.0001, 95%CI 0.31 - 0.66) comparing to control. The null and GSTMT genotype had no significant statistical differences between the two groups. Conclusion : ADC patients were found to have a higher incidence of the GSTM genotype and a lower incidence of the GSTT genotype, compared to controls. Future studies may help elucidate the possible contribution of these genotypic differences in lung adenocarcinoma carcinogenesis or regarding the response to chemotherapy.