Carcinogenesis, Vol. 22, No. 8, 1327-1329,
August 2001
© 2001 Oxford University Press
SHORT COMMUNICATION |
Glutathione S-transferase µ1 null genotype is associated with K-ras gene mutation in lung adenocarcinoma among smokers
Second Department of Surgery, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonanku, Fukuoka 814-0180, Japan,
1 Division of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA and
2 Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda Surugadai, Chiyodaku, Tokyo 101-0062, Japan
Glutathione S-transferase µ1 (GSTM1) plays a role in the detoxification of benzo[a]pyrene (BP) diol epoxide in tobacco smoke. Individuals who genetically lack the GSTM1 gene are likely to have an increased risk of smoking-related lung cancers, however, the target oncogenes for mutation are unknown. To investigate the relation between GSTM1 genotype and K-ras gene mutation we examined 193 adenocarcinomas and 119 squamous cell carcinomas of lung. The GSTM1 genotype was determined by PCR and K-ras gene mutations at codons 12 and 13 were detected by dot-blot hybridization analysis using sequence-specific oligonucleotide probes. K-ras gene mutations were found in 29 of 312 (9.3%) tumors. All of them arose in patients who were habitual smokers. Mutations of the K-ras gene were detected in 6 of 100 (6%) and 15 of 93 (16.1%) adenocarcinoma cases with the GSTM1(+) and GSTM1(–) genotypes, respectively, and the difference was statistically significant. These findings suggest that the cause of K-ras gene mutation in smokers with lung adenocarcinoma may be in part an accumulation of BP diol epoxide which is not well detoxified in individuals with the GSTM1 null genotype.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Carlsten, G. S. Sagoo, A. J. Frodsham, W. Burke, and J. P. T. Higgins Glutathione S-Transferase M1 (GSTM1) Polymorphisms and Lung Cancer: A Literature-based Systematic HuGE Review and Meta-Analysis Am. J. Epidemiol., April 1, 2008; 167(7): 759 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-M. Gao, M. Romkes, J. M. Siegfried, J. D. Luketich, and P. Keohavong No Association between the XPD 312, 751, or XRCC1 399 Polymorphisms and K-ras Gene Mutation in Smoking Non-Small-Cell Lung Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 673 - 675. [Full Text] [PDF]
|
|
|
|
|
|
C. Sweeney, V. Nazar-Stewart, P. L. Stapleton, D. L. Eaton, and T. L. Vaughan Glutathione S-transferase M1, T1, and P1 Polymorphisms and Survival among Lung Cancer Patients Cancer Epidemiol. Biomarkers Prev., June 1, 2003; 12(6): 527 - 533. [Abstract] [Full Text] [PDF]
|
|