The role of phase I and II genetic polymorphisms, smoking, alcohol and cancer family history, in the risk of developing testicular cancer
| Autor: | Elena García-Martín, Juan Carlos Rubilar, Dante Cáceres, Ángela Roco, Juan P Cayún, Cristian Acevedo, José A. G. Agúndez, Berta Cerda, Christopher Sandoval, Gemma Amo, Alejandra Lavanderos, Angelo Canepa, Gara Esguevillas, Nelson Varela, Leslie Cerpa, Cesar Celedón, Luis A. Quiñones, Karina Peña |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Adolescent Alcohol Drinking Bioinformatics digestive system 030226 pharmacology & pharmacy Polymorphism Single Nucleotide 03 medical and health sciences Young Adult 0302 clinical medicine Cytochrome P-450 Enzyme System Testicular Neoplasms Detoxification Genetics medicine Humans Genetic Predisposition to Disease General Pharmacology Toxicology and Pharmaceutics Family history Chile Glucuronosyltransferase Molecular Biology Gene Genetics (clinical) Testicular cancer Aged Glutathione Transferase Aged 80 and over biology business.industry Incidence (epidemiology) Smoking Cytochrome P450 Cancer Middle Aged medicine.disease Alcohol and cancer 030104 developmental biology biology.protein Molecular Medicine business |
| Zdroj: | Pharmacogenetics and genomics. 29(7) |
| ISSN: | 1744-6880 |
| Popis: | 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.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.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.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.Therefore, phase I and II variant alleles might be useful in evaluating susceptibility to TCa in the studied population. |
| Databáze: | OpenAIRE |
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