TITLE:
Polymorphisms of GSTs in Lung Adenocarcinoma Patients Followed in the Context of a Biobank
AUTHORS:
Fotis Vlastos, Georgios Hillas, Nektarios Anagnostopoulos, Jean Michel Vignaud, Nadine Martinet, Nikolaos G. Koulouris
KEYWORDS:
GSTs; Molecular Signature; Lung Adenocarcinoma; Lung Cancer Risk
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.8A,
August
21,
2013
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.