The role of phase I and II genetic polymorphisms, smoking, alcohol and cancer family history, in the risk of developing testicular cancer. Issue 7 (September 2019)

• Record Type: Journal Article
• Authors: Roco, Angela; Lavanderos, Alejandra; Cayún, Juan P.; Acevedo, Cristian; Celedón, Cesar; Rubilar, Juan C.; Sandoval, Christopher; Cerpa, Leslie; García-Martín, Elena; Agúndez, Jose A.; Esguevillas, Gara; Amo, Gemma; Canepa, Angelo; Cerda, Berta; Peña, Karina; Cáceres, Dante D.; Varela, Nelson M.; Quiñones, Luis A.
• Is Part Of: Pharmaocogenetics and genomics. Volume 29:Issue 7(2019)
• Publication Date: 2019-09
• Subjects: CYP -- glutathione-S-transferases -- pharmacogenetics -- polymorphisms -- susceptibility -- testicular cancer -- UDP glucuronyl transferases; Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000379
• Languages: English
• ISSNs: 1744-6872

Abstract

Abstract : 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.