This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goto, I. Articles by Kawajiri, K. Search for Related Content PubMed PubMed Citation Articles by Goto, I. Articles by Kawajiri, K.

Prognostic Significance of Germ Line Polymorphisms of the CYP1A1 and Glutathione S-Transferase Genes in Patients with Non-Small Cell Lung Cancer¹

Pulmonary Medicine Clinic [I. G., S. Y.] and Thoracic Surgery Clinic [M. Y.], Saitama Cancer Center Hospital, and Department of Biochemistry [K. K.], Saitama Cancer Center Research Institute, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362, Japan

CYP1A1 is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke, and high susceptibility to smoking-related lung cancer has been associated with the MspI polymorphism of the CYP1A1 gene. Individuals with a susceptible CYP1A1 genotype have been found to be at remarkably high risk when the genotype is combined with a deficient Mu-class glutathione S-transferase (GSTM1) genotype. In this study, we investigated the relationship between germ line polymorphisms of these genes and clinical characteristics or survival rates in 232 patients with non-small cell lung cancer (NSCLC). Statistical analysis revealed a significant association (P < 0.05) of the MspI polymorphism of the CYP1A1 gene with histological type, performance status (general conditions of patients), and the extent of the primary tumor (T-factor). On the other hand, the GSTM1 polymorphism was significantly associated with performance status, the extent of regional lymph node metastasis (N-factor), and the extent of distant metastasis (M-factor). NSCLC patients with at least one susceptible allele of the MspI polymorphism of the CYP1A1 gene [heterozygous genotype B or a rare homozygous genotype C; n = 131; median survival time (MST) = 24.2 months] were associated with a shortened survival compared with those with nonsusceptible homozygous alleles (genotype A; n = 101; MST = 65.2 months; P = 0.005 by log-rank test). Smokers with susceptible genotypes (n = 104; MST = 18.2 months) were markedly associated with a shortened survival compared with those with genotype A (n = 76; MST = 69.2 months; P = 0.024); such an association was not found among nonsmokers by genotypes. Genotype-dependent survival was also observed in patients at an advanced stage of disease (P = 0.010), but not in those at an early stage of disease (P = 0.382). Patients with the susceptible CYP1A1 genotype had remarkably shortened survivals when the genotype was combined with a deficient genotype GSTM1(—) (P = 0.017; degree of freedom = 3). Multivariate analysis by the Cox proportional hazards model also revealed that the CYP1A1 polymorphism was an independent prognostic factor in patients at a nonresectable advanced stage of NSCLC (P = 0.005; hazard ratio = 1.98; 95% confidence interval, 1.24–3.17).

¹ Supported in part by a special grant for advanced research on cancer from the Ministry of Education, Science, Sports and Culture of Japan and a research grant from the Ministry of Health and Welfare of Japan for 2nd-Term Comprehensive 10-Year Strategy for Cancer Control.

² To whom requests for reprints should be addressed. Fax: 81-48-722-1739.

Received 1/30/96. Accepted 6/18/96.

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]

				P. J Mazzone, J. Hammel, R. Dweik, J. Na, C. Czich, D. Laskowski, and T. Mekhail Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array Thorax, July 1, 2007; 62(7): 565 - 568. [Abstract] [Full Text] [PDF]

				A. G. Schwartz, G. M. Prysak, C. H. Bock, and M. L. Cote The molecular epidemiology of lung cancer Carcinogenesis, March 1, 2007; 28(3): 507 - 518. [Abstract] [Full Text] [PDF]

				P. Yang, J. O. Ebbert, Z. Sun, and R. M. Weinshilboum Role of the Glutathione Metabolic Pathway in Lung Cancer Treatment and Prognosis: A Review J. Clin. Oncol., April 10, 2006; 24(11): 1761 - 1769. [Abstract] [Full Text] [PDF]

				P. J. Mazzone, T. Mekhail, and A. C. Arroliga Is Lung Cancer in the Nonsmoker a Different Disease? Chest, August 1, 2004; 126(2): 326 - 329. [Full Text] [PDF]

				P. Barnette, R. Scholl, M. Blandford, L. Ballard, A. Tsodikov, J. Magee, S. Williams, M. Robertson, F. Ali-Osman, R. Lemons, et al. High-Throughput Detection of Glutathione S-Transferase Polymorphic Alleles in a Pediatric Cancer Population Cancer Epidemiol. Biomarkers Prev., February 1, 2004; 13(2): 304 - 313. [Abstract] [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]

				M. D. Brundage, D. Davies, and W. J. Mackillop Prognostic Factors in Non-small Cell Lung Cancer* : A Decade of Progress Chest, September 1, 2002; 122(3): 1037 - 1057. [Abstract] [Full Text] [PDF]

				S. M. Schwartz, D. R. Doody, E. D. Fitzgibbons, S. Ricks, P. L. Porter, and C. Chen Oral Squamous Cell Cancer Risk in Relation to Alcohol Consumption and Alcohol Dehydrogenase-3 Genotypes Cancer Epidemiol. Biomarkers Prev., November 1, 2001; 10(11): 1137 - 1144. [Abstract] [Full Text] [PDF]

				G. B. J. Smith, P. A. Harper, J. M. Y. Wong, M. S. M. Lam, K. R. Reid, D. Petsikas, and T. E. Massey Human Lung Microsomal Cytochrome P4501A1 (CYP1A1) Activities: Impact of Smoking Status and CYP1A1, Aryl Hydrocarbon Receptor, and Glutathione S-Transferase M1 Genetic Polymorphisms Cancer Epidemiol. Biomarkers Prev., August 1, 2001; 10(8): 839 - 853. [Abstract] [Full Text] [PDF]

				P. G. Shields and C. C. Harris Cancer Risk and Low-Penetrance Susceptibility Genes in Gene-Environment Interactions J. Clin. Oncol., June 11, 2000; 18(11): 2309 - 2315. [Abstract] [Full Text] [PDF]

				S.-M. Hou, D. Ryberg, S. Falt, A. Deverill, T. Tefre, A.-L. Borresen, A. Haugen, and B. Lambert GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients Carcinogenesis, January 1, 2000; 21(1): 49 - 54. [Abstract] [Full Text] [PDF]

				G. Romano, A. Sgambato, A. Boninsegna, G. Flamini, G. Curigliano, Q. Yang, V. La Gioia, C. Signorelli, A. Ferro, G. Capelli, et al. Evaluation of Polycyclic Aromatic Hydrocarbon-DNA Adducts in Exfoliated Oral Cells by an Immunohistochemical Assay Cancer Epidemiol. Biomarkers Prev., January 1, 1999; 8(1): 91 - 96. [Abstract] [Full Text]