Increased Risk of Acute Myeloid Leukemia in Patients with CYP1A1 Polymorphisms


Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p < 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p < 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.

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L. Pelloso, I. Silva, N. Souza, M. Yamamoto and M. Chauffaille, "Increased Risk of Acute Myeloid Leukemia in Patients with CYP1A1 Polymorphisms," Journal of Cancer Therapy, Vol. 4 No. 5, 2013, pp. 971-977. doi: 10.4236/jct.2013.45111.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] S. H. Swerdlow, E. Campo, N. L. Harris, et al., “WHO Classifiction of Tumours of Haematopoietic and Lymphoid Tissues,” IARC Press, Lyon, 2008.
[2] S. Rollinson, P. Roddam, E. Kane, E. Roman, R. Cartwright, A. Jack and G. J. Morgan, “Polymorphic Variation within the Glutathione S-Transferase Genes and Risk of Adult Acute Leukemia,” Carcinogenesis, Vol. 21, No. 1, 2000, pp. 43-47. doi:10.1093/carcin/21.1.43
[3] S. S. Franco, A. C. Nardocci and W. M. Günther, “PAH Biomarkers for Human Health Risk Assessment: A Review of the State-of-the-Art,” Cadernos de Saúde Pública, Vol. 24, Supplement 4, 2008, pp. s569-s580.
[4] I. Cascorbi, J. Brockm?ller and I. Roots, “A C4887A Polymorphism in Exon 7 of Human CYP1A1: Population Frequency, Mutation Linkages, and Impact No Lung Cancer Suscepbtility,” Cancer Research, Vol. 56, No. 21, 1996, pp. 4965-4969.
[5] Y. Li, R. C. Millikan, D. A. Bell, L. Cui, C. K. T. Tse, B. Newman and K. Conway, “Cigarette Smoking, Cytochrome P4501 Polymorphisms, and Breast Cancer among African-American and White Women,” Breast Cancer Research, Vol. 6, No. 4, 2004, pp. R460-R473. doi:10.1186/bcr814
[6] R. Montero, A. Araujo, P. Carranza, V. Mejía-Loza, L. Serrano, A. Albores, J. E. Salinas and R. Camacho-Carranza, “Genotype Frequencies of Polymorphic GSTM1, GSTT1, and Cytochrome P450 CYP1A1 in Mexicans,” Vol. 79, No. 3, 2007, pp. 299-312.
[7] M. T. Voso, F. D’Alo, R. Putzulu, L. Mele, A. Scardocci, P. Chiusolo, et al., “Negative Prognostic Value of Glutathione S-Transferase (GSTM1 and GSTT1) Deletions in Adult Acute Myeloid Leukemia,” Blood, Vol. 100, No. 8, 2002, pp. 2703-2707. doi:10.1182/blood.V100.8.2703
[8] P. Bolufer, M. Collado, E. Barragan, M. J. Calasanz, D. Colomer, M. Tormo, M. González, S. Brunet, M. Batlle, J. Cervera and M. A. Sanz, “Profile of Polymorphisms of Drug-Metabolising Enzymes and the Risk of TherapyRelated Leukaemia,” British Journal of Haematology, Vol. 36, No. 4, 2007, pp. 590-596. doi:10.1111/j.1365-2141.2006.06469.x
[9] L. A. F. Pelloso, I. D. C. G. Silva, N. C. R. Souza, C. A. A. Botelho, M. Yamamoto and M. L. L. F. Chauffaille, “CYP1A1 Polymorphisms Modify Overall Survival in Acute Myeloid Leukemia Patients,” Leukemia and Lymphoma, Vol. 48, No. 6, 2007, pp. 1211-1215. doi:10.1080/10428190701332431
[10] A. P. Singh, P. P. Shah, M. Ruwali, N. Mathur, M. C. Pant and D. Parmar, “Polymorphism in Cytochrome P4501A1 is Significantly Associated with Head and Neck Cancer Risk,” Cancer Investigation, Vol. 27, No. 8, 2009, pp. 869-876. doi:10.1080/07357900902849657
[11] C. M. Wright, J. E. Larsen, M. L. Colosimo, J. J. Barr, L. Chen, R. E. McLachlan, I. A. Yang, R. V. Bowman and K. M. Fong, “Genetic Association Study of CYP1A1 Polymorphisms Identifies Risk Haplotypes in Nonsmall Cell Lung Cancer,” European Respiratory Journal, Vol. 35, No. 1, 2010, pp. 152-159. doi:10.1080/07357900902849657
[12] M. L. L. F. Chauffaille, M. S. Figueiredo, R. Beltrani, et al., “Acute Promyelocytic Leukemia: The Study of t(15;17) Translocation by Fluorescent in Situ Hybridization, Reverse Transcriptase-Polymearse Chain Reaction and Cytogentic Techniques,” Brazilian Journal of Medical and Biological Research, Vol. 34, No. 6, 2001, pp. 735-743. doi:10.1590/S0100-879X2001000600006
[13] D. Grimwade, H. Walker, G. Harrison, F. Oliver, S. Chatters, et al., “The Predicitive Value of Hierarchial Cytogenetic Classification in Older Patients with Acute Myeloid Leukemia (AML): Analysis of 1065 Patients Entered into the United Kingdom Medical Research Council AML11 Trial,” Blood, Vol. 98, No. 5, 2001, pp. 1312-1320. doi:10.1182/blood.V98.5.1312
[14] G. J. F. Gattás and J. A. Soares-Vieira, “Cytochrome P450-2E1 and Glutathione S-Transferase um Polymorphims among Caucasians and Mulattoes from Brazil,” Occupational Medicine, Vol. 50, No. 7, 2000, pp. 508-511. doi:10.1093/occmed/50.7.508
[15] G. J. F. Gattás, M. Kato, J. A. Soares-Vieira, M. S. Siraque, P. Kohler, L. Gomes, M. A. V. Rego and S. P. Bydlowski, “Ethnicity and Glutathione S-Transferase (GSTM1/ GSTT1) Polymorphisms in a Brazilian Population,” Brazilian Journal of Medical and Biological Research, Vol. 37, No. 4, 2004, pp. 451-458. doi:10.1093/occmed/50.7.508
[16] F. D’Alò, M. T. Voso, F. Guidi, G. Massini, A. Scardocci, S. Sica, L. Pagano, S. Hohaus and G. Leone, “Polymorphisms of CYP1A1 and Glutathione S-Transferase and Susceptbility to Adult Acute Myeloid Leukemia,” Haematologica, Vol. 89, No. 6, 2004, pp. 664-670.
[17] V. R. Arruda, C. S. P. Lima, C. R. E. Grignoli, M. B. Melo, I. Lorand-Metze, F. L. Alberto, S. T. O. Saad and F. F. Costa, “Increased Risk for Acute Myeloid Leukaemia in Individulas with Glutathione S-Transferase mu 1 (GSTM1) and Theta 1 (GSTT10) gene Defects,” European Journal of Haematology, Vol. 66, No. 6, 2001, pp. 383-388. doi:10.1093/occmed/50.7.508
[18] T. Basu, R. E. Gale, C. Fidler, P. E. Peto, J. Boutwood and J. S. Wainscoat, “Glutahione S-Transferase Theta 1 (GSTT1) Gene Defect in Myelodysplasia and Acute Myeloid Leukemia,” Lancet, Vol. 349, No. 9063, 1997, p. 1450. doi:10.1093/occmed/50.7.508
[19] M. H. Woo, J. J. Shuster and C. Chen, “Glutathione S-Transferase Genotypes in Children Who Developed Treatment Related Acute Myeloid Malignancies,” Leukemia, Vol. 14, No. 2, 2000, pp. 232-237. doi:10.1038/sj.leu.2401660
[20] L. A. Pelloso, M. L. Chauffaille, F. S. Ghaname, M. Yamamoto, D. M. Bahia, J. Kerbauy, “Karyotype in Acute Myeloid Leukemia: Importance and Type of Aberrations in 30 Patients at Diagnosis,” Revista da Associa??o Médica Brasileira, Vol. 49, No. 2, 2003, pp. 150-155. doi:10.1590/S0104-42302003000200032
[21] C. A. Rodrigues, M. L. Chauffaille, L. A. Pelloso, F. S. Ghaname, D. M. Kerbauy, M. G. Campos and M. Yamamoto, “Acute Myeloid Leukemia in Elderly Patients: Experience of a Single Center,” Brazilian Journal Of Medical and Biological Research, Vol. 36, No. 6, 2003, pp. 703-708. doi:10.1590/S0100-879X2003000600004
[22] M. L. Slovak, K. J. Kopecky, D. Cassileth, D. H. Harrington, K. S. Thiel, A. Mohamed, et al., “Karyotypic Analysis Predicts Outcome of Preremission and Postremission Therapy in Adult Acute Myeloid Leukemia: A Southwest Oncology Group/Eastern Cooperative Oncology Group Study,” Blood, Vol. 96, No. 13, 2000, pp. 4075-4083.

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