The role of phase I and II genetic polymorphisms, smoking, alcohol and cancer family history, in the risk of developing testicular cancer.
| Autor: | Roco A; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile.; Faculty of Life Sciences, Andrés Bello University., Lavanderos A; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., Cayún JP; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., Acevedo C; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile.; University of Chile Clinical Hospital., Celedón C; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., Rubilar JC; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., Sandoval C; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., Cerpa L; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., García-Martín E; Department of Pharmacology, University of Extremadura. ARADyAL Instituto de Salud Carlos III, Cáceres. Spain., Agúndez JA; Department of Pharmacology, University of Extremadura. ARADyAL Instituto de Salud Carlos III, Cáceres. Spain., Esguevillas G; Department of Pharmacology, University of Extremadura. ARADyAL Instituto de Salud Carlos III, Cáceres. Spain., Amo G; Department of Pharmacology, University of Extremadura. ARADyAL Instituto de Salud Carlos III, Cáceres. Spain., Canepa A; San Juan de Dios Hospital., Cerda B; National Cancer Institute., Peña K; San Juan de Dios Hospital., Cáceres DD; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile.; Institute of Population Health, Faculty of Medicine, University of Chile Santiago.; Faculty of Life Sciences, University of Tarapaca, Arica, Chile., Varela NM; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile., Quiñones LA; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile. |
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| Jazyk: | angličtina |
| Zdroj: | Pharmacogenetics and genomics [Pharmacogenet Genomics] 2019 Sep; Vol. 29 (7), pp. 159-166. |
| DOI: | 10.1097/FPC.0000000000000379 |
| Abstrakt: | Background: Testicular cancer (TCa) is a malignant tumor with highest incidence and mortality rates in Chile. The genes coding for cytochrome P450, glutathione-S-transferases (GSTs), and UDP glucuronyl transferases (UGT) participate in the biotransformation and detoxification of xenobiotics. Mutations in these genes have been associated with a high incidence of various types of cancer and an increased risk of presenting adverse reactions to drugs. Objective: The aim of this study was to relate the presence of genetic polymorphisms in cytochrome P450 1A1 (CYP1A1), CYP3A4, GSTM1, GSTP1, GSTT1, and UGT1A1 genes and nongenetic factors with the risk of developing TCa. Methods: A total of 276 volunteers from the Chilean general population and 251 Chilean TCa patients were recruited for the study. Genotypic analyses were performed using qPCR and PCR-RFLP. Results: Variant alleles found to increase the risk of developing TCa were CYP1A1*2C (rs1048943), GSTP1 (rs1695), and GSTT1null, especially when in conjunction with a cancer family history and/or a smoking habit. The results of the multivariate analysis showed that the presence of variant alleles of GSTP1 (rs1695) together with a smoking habit and a family history of cancer accounted for a 15.9% risk of developing TCa in the Chilean population. CYP1A1*2C, GSTM1null, GSTT1null, and GSTP1 (rs1695) are statistically related to the risk of appearance of TCa, alone or associated with nongenetic factors. Conclusion: Therefore, phase I and II variant alleles might be useful in evaluating susceptibility to TCa in the studied population. |
| Databáze: | MEDLINE |
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