Resumen
El tabaco es la principal causa del cáncer de pulmón, pero el hecho de que sólo el 10%–15% de los fumadores desarrollen un tumor nos indica que existen diferencias individuales en el metabolismo de los carcinógenos presentes en el humo de tabaco, que predisponen de forma diferente a padecer la enfermedad. En esta revisión nos centraremos en los resultados de los estudios epidemiológicos caso-control sobre los polimorfismos de las enzimas que metabolizan carcinógenos del tabaco, como el citocromo P450 (gen CYP1A1), las glutatión S-transferasas (GST) y las N-acetil transferasas (NAT), y que contribuyen a la susceptibilidad genétical individual al cáncer de pulmón.
Abstract
Tobacco smoking is the most important etiological factor in lung cancer. But the fact that only 10%–15% of lifetime smokers develop a cancer indicates that there are individual variations in the metabolism of the tobacco smoke carcinogens that predispose in a different way to suffer the disease. This review gives an, overview on results of epidemiological case-control studies about polymorphisms of cigarette smoke drugs metabolising enzymes, namely cytochrome P450 (CYP1A1 gene), glutathione S-transferases (GSTs) and N-acetyl-transferases (NATs), that have been shown to influence individual genetic susceptibility to lung cancer.
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Parkin DM, Whelan SL, Ferlay J, Raymons L, Young, eds. Cancer incidence in five continets. Lyon (France): IARC Sci Publ, 1997; 143.
Cueto A, Tardón A, Delgado M. Epidemiología del cáncer. En: Gálvez R, Sierra A y Sáez MC, ed. Piédrola Gil Medicina Preventiva y Salud Pública (10.a ed). Barcelona: Masson, SA, 2001; 689–702.
Travis WD, Lubin J, Ries L, Devesa S. United States lung carcinoma incidence trends. Cancer 1996; 77: 2.464–2.470.
Greenlee RT, Mirray T, Bolden S, Wingo PA. Cancer statistics, 2000. Cancer J Clin 2000; 50:7–33.
Blot JW Fraumeni Jr JF. Cancers of the lung and pleura. En: Schottenfeld D, Fraumeni JF, eds. Cancer epidemiology and prevention. Oxford: Oxford University Press, 1996; 1.156–1.179.
Alavanja MCR, Lubin JH, Mahaffey JA, Browson RC. Residencial radon exposure and risk of lung cancer in Missouri. Am J Public Health 1999; 89: 1.042–1.048.
Brüske-Hohfeld I, Möhner M, Pohlabeln H, et al. Occupational lung cancer risk for men in Germany: Results from a pooled case-control study. Am J Epidemiol 2000; 151: 384–395.
Rodríguez V, Tardón A, Kogevinas M, et al. Lung cancer risk in iron and steel industry. A nested case control in Asturias. Am J Ind Med 2000; 38: 644–650.
Boffeta P, Kogevinas M. Epidemiologic research and prevention of occupational cancer in Europe. Environ Health Perspect 1999; 107 (Supl 2): 229–231.
Voorrips LE, Golbohm A, Verhveven D, et al. Vegetable and fruit consumption and lung cancer risk in the Netherlands cohort study on diet and cancer. Cancer Causes Control 2000; 11: 101–115.
Rosell R. New approaches in the adjuvant and neoadyuvant therapy of non-small cell lung cancer, including docetaxel (Taxotere) combinations. Sem Oncol 1999; 26: 32–37.
Rosell R, Felip E. Role of multimodality treatment for lung cancer. Semin Surg Oncol 2000; 18: 143–151.
Bepler G. Lung cancer epidemiology and genetics. J Thorac Imaging 1999; 14: 228–234.
Haugen A, Ryberg D, Mollerup S, Zienolddiny S, Skaug V, Svendsrud DH. Gene-enviroment interactions in human lung cancer. Toxicol Lett 2000; 112–113: 233–237.
Bartsch H, Hietanen E. The role of individual susoeptibility in cancer burden related to environmental exposure. Env Health Persp 1996; 104: 569–577.
Perera FP. Environmental and cancer: who are susceptible? Science 1997; 278: 1.068–1.073.
Ladero, JM, García-Agúndez JA, Benítez J. Polimorfismos enzimáticos y cáncer de pulmón. Med Clín (Barc) 1998; 111: 465–470.
Ryberg D, Kure E, Lystad S, et al. p53 mutations in lung tumors: relationship to putative susceptibility markers for cancer. Cancer Res 1994; 54: 1.551–1.555.
Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994; 54: 4.855–4.878.
Rosell R, Monzó M, Pifarré A, et al. Molecular staging of non-small cell lung cancer according to K-ras genotypes. Clin Cancer Res 1996; 2: 1.083–1.086.
Hengstler JG, Arand M, Herrero ME, Oesch F. Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal expoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Rec Res Cancer Res 1998; 154: 47–85.
Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomark Prev 2000; 9: 3–28.
Houlston RS. CYP1A1 polymorphisms and lung cancer risk: a metaanalysis. Pharmacogenetics 2000; 10: 105–114.
Strange RC, Fryer AA. Chapter 1. The glutathione S-transferases: influence of polymorphism on cancer susceptibility. IARC Sci Publ (1999); 148: 231–249.
Attila S, Hirvonen A, Vainio H, Husgafvel-Pursiainen K, Hayes JD, Ketterer B. Immunohistochemical localization of glutathione S-transferases in human lung. Cancer Res 1993; 53: 5.643–5.648.
Anttila S, Luostarinen L, Hirvonen A, et al. Pulmonary expression of glutathione S-transferase M3 in lung cancer patients: association with GSTM1 polymorphism, smoking, and asbestos exposure. Cancer Res 1995; 55: 3.305–3.309.
Randerath E, Miller RH, McHal D, Avitts TA, Dunsford HA, Randerath K. Covalent DNA damage in tissues of cigarette smokers as determined by32P-postlaeling assay. J Natl Cancer Inst 1989; 81: 341–347.
McWilliams JE, Sanderson BJ, Harris EL, Richert-Boe KE, Henner WD. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomark Prev 1995; 4: 589–594.
Houlston RS. Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 1999; 8: 675–682.
London SJ, Daly AK, Cooper J, Navidi WC, Carpenter CL, Idle JR. Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles county, California. J Natl Cancer Inst 1995; 87: 1.246–1.253.
Bennett WP, Alavanja MCR, Blomeke B, et al. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. J Natl Cancer Inst 1999; 91: 2.009–2.014.
Malats N, Camus-Radon AM, Nyberg F et al. Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism. Cancer Epidemiol Biomark Prev 2000; 9: 827–833.
Saarikoski ST, Voho A, Reinikainen M et al. Combined effect of polymorphic GST genes on individual susceptibility to lung cancer. Int J Cancer 1998; 77: 516–521.
To-Figueras J, Gené M, Gómez-Catalán J, et al. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms and lung cancer risk among Northwestern Mediterraneans. Carcinogenesis 1997; 18: 1.529–1.533.
To-Figueras J, Gené M, Gómez-Catalán J, et al. Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk. Cancer Causes Control 1999; 10: 65–70.
Hein DW, Doll MA, Fretland AJ, et al. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomark Prev 2000; 9: 29–42.
Cascorbi I, Brockmöller J, Mrozikiewicz PM, Bauer S, Loddenkemper R, Roots I. Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer. Cancer Res 1996; 56: 3.961–3.966.
Nyberg F, Hou S, Hemminki K, Lambert B, Pershagen G. Glutathione S-transferase μ1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls. Cancer Epidemiol Biomark Prev 1998; 7: 875–883.
Raunio H, Husgafvel-Pursiainen K, Anttila S, Hietanen E, Hirvonen A, Pelkonen O. Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility- a review. Gene 1995; 159: 113–121.
Kihara M, Kihara M, Noda K. Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population. Carcinogenesis 1995; 16: 2.331–2.336.
García-Closas M, Kelsey KT, Wiencke JK, Xu X, Wain JC, Christiani DC. A case-control study of cytochrome P450 1A1, glutathione S-transferase M1 cigarette smoking and lung cancer susceptibility (Massachusetts, United States). Cancer Causes Control 1997; 8: 544–553.
Vaury C, Laine R, Noguiez P et al. Human glutathione S-transferase M1 null genotype is associated with high inducibility of cytochrome P450 1A1 gene transcription. Cancer Res 1995; 55: 5.520–5.523.
Hou S, Ryberg D, Fält D, et al. GSTM1 and NAT2 poly-morphisms in operable and non-operable lung cancer patients. Carcinogenesis 2000; 21: 49–54.
Goto I, Yoneda S, Yamamoto M, Kawajiri K. Prognostic significance of germ line polymorphisms of the CYP1A1 and glutathione S-transferase genes in patients with non-small cell lung cancer. Cancer Res 1996; 56: 3.725–3.730.
Huang Ch, Taki T, Adachi M, Konishi T, Higashiyama M, Miyake M. Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer. Oncogene 1998; 16: 2.469–2.477.
Bartsch H, Rojas M, Nair U, Nair J, Alexandrov K. Genetic cancer susceptibility and DNA adducts: studies in smokers, tobacco chewers, and coke oven workers. Cancer Det Prev 1999; 23 445–453.
Rojas M, Cascorbi I, Alexandrov K, et al. Modulation of benzo(a)pyrene diolepoxide-DNA adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism. Carcinogenesis 2000; 21: 35–41.
Husgafvel-Pursiainen K, Kannio A, Oksa P, et al. Mutations, tissue accumulations, and serum levels of p53 in patients with occupational cancers from asbestos and silica exposure. Env Mol Mut 1997; 30: 224–230.
Sekido Y, Fong KM, Minna JD. Progress in understan-CYP1A1, GST, NAT, DNA adducts, p53.
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Marín, M.S., Tardón, A. & Martínez, B. Susceptibilidad genética individual y alteraciones moleculares en el cáncer de pulmón. Rev Oncol 3, 121–129 (2001). https://doi.org/10.1007/BF02711437
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DOI: https://doi.org/10.1007/BF02711437
Palabras clave
- cáncer de pulmón
- epidemiología molecular
- susceptibilidad genética individual
- polimorfismo
- CYPA1
- GST
- NAT
- aductos de ADN
- p53