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

DOI: 10.4236/jct.2013.48A004   PDF   HTML   XML   2,858 Downloads   3,995 Views   Citations


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.

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Vlastos, F. , Hillas, G. , Anagnostopoulos, N. , Vignaud, J. , Martinet, N. and Koulouris, N. (2013) Polymorphisms of GSTs in Lung Adenocarcinoma Patients Followed in the Context of a Biobank. Journal of Cancer Therapy, 4, 24-28. doi: 10.4236/jct.2013.48A004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. Ferlay, E. Steliarova-Foucher, J. Lortet-Tieulent, S. Rosso, J. W. Coebergh, H. Comber, D. Forman and F. Bray, “Cancer Incidence and Mortality patterns in Europe: Estimates for 40 Countries in 2012,” European Journal of Cancer, Vol. 49, No. 6, 2013, pp. 1374-1403. doi:10.1016/j.ejca. 2012.12.027
[2] B. W. Stewart and P. Kleihues, “World Cancer Report,” IARC Press, Lyon, 2003.
[3] M. R. Spitz, Q. Wei, Q. Dong, et al., “Genetic Susceptibility to Lung Cancer: The Role of DNA Damage and Repair,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 12, No. 8, 2003, pp. 689-698.
[4] International Association for the Study of Lung Cancer/ American Thoracic Society/European Respiratory Society, “International Multidisciplinary Classification of Lung Adenocarcinoma,” Journal of Thoracic Oncology, Vol. 6, No. 2, 2011, pp. 244-285. doi:10.1097/JTO.0b013e318206a221
[5] M. P. Curado, B. Edwards, H. R. Shin, et al., “Cancer Incidence in Five Continents,” Vol. IX, IARC Scientific Publications, Lyon, 2007.
[6] W. D. Travis, E. Brambilla, H. K. Muller-Hermelink, et al., “Pathology and Genetics. Tumours of the Lung, Pleura, Thymus and Heart,” IARC Press, Lyon, 2004.
[7] M. J. Thun, C. A. Lally, J. T. Flannery, et al., “Cigarette Smoking and Changes in the Histopathology of Lung Cancer,” Journal of the National Cancer Institute, Vol. 89, No. 21, 1997, pp. 1580-1586. doi:10.1093/jnci/89.21.1580
[8] A. Charloux, E. Quoix, N. Wolkove, et al., “The Increasing Incidence of Lung Adenocarcinoma: Reality or Artifact? A Review of the Epidemiology of Lung Adenocarcinoma,” International Journal of Epidemiology, Vol. 26, No. 1, 1997, pp. 14-23. doi:10.1093/ije/26.1.14
[9] F. Claudot, N. Malservet, C. Gallina-Muller, et al., “Le Centre de Ressources Biologiques Oncogenèse Thoracique,” Bull Cancer, Vol. 91, 2004, pp. 201-203.
[10] P. D. Josephy, “Genetic Variations in Human Glutathione Transferase Enzymes: Significance for Pharmacology and Toxicology,” Hum Genomics Proteomics, Vol. 2010, 2010, Article ID: 876940.
[11] J. D. Hayes, J. U. Flanagan and I. R. Jowsey, “Glutathione Transferases,” Annual Review of Pharmacology and Toxicology, Vol. 45, 2005, pp. 51-88. doi:10.1146/annurev.pharmtox.45. 120403.095857
[12] E. Brambilla, W. D. Travis, T. V. Colby, et al., “The New World Health Organization Classification of Lung Tumours,” European Respiratory Journal, Vol. 18, No. 6, 2001, pp. 1059-1068. doi:10.1183/09031936.01.00275301
[13] L. H. Sobin and C. Wittekind, “International Union against Cancer (UICC), TNM Classification of Malignant Tumors,” 6th Edition, Wiley-Liss, New York, 2002, pp. 99-103.
[14] L. C. Strong and C. I. Amos, “Inherited Susceptibility,” In: D. Schottenfeld, J. G. Searle, J. F. Fraumeni Jr., Eds., Cancer Epidemiology and Prevention, Oxford University Press, New York, 1996, pp. 559-582.
[15] S. Kato, E. D. Browman, A. M. Harrigan, et al., “Human Lung Carcinogen-DNA Adduct Levels Mediated by Genetic Polymorphism in Vivo,” Journal of the National Cancer Institute, Vol. 87, No. 12, 1995, pp. 902-907. doi:10.1093/jnci/87.12.902
[16] J. W. Wang, Y. F. Deng, et al., “Association of GSTM1, CYP1A1 and CYP2E1 Genetic Polymorphisms with Susceptibility to Lung Adenocarcinoma: A Case-Control Study in Chinese Population,” Cancer Science, Vol. 94, No. 5, 2003, pp. 448-452. doi:10.1111/j.1349-7006.2003.tb01463.x

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