The role of phase I and II genetic polymorphisms, smoking, alcohol and cancer family history, in the risk of developing testicular cancer

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; et. al.

Keywords: Pharmacogenetics, susceptibility, testicular cancer, polymorphisms, CYP, GST, UGT

Abstract

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 (ADR). The aim of this study was to relate the presence of genetic polymorphisms in CYP1A1, CYP3A4, GSTM1, GSTP1, GSTT1, and UGT1A1 genes and non-genetic factors with the risk of developing testicular cancer. A total of 276 volunteers from the Chilean general population (PCh) 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 cancer family history and/or 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 testicular cancer in the Chilean population. CYP1A1*2C, GSTM1null, GSTT1null, and GSTP1(rs1695) are statistically related to the risk of appearance of testicular cancer, alone or associated with non-genetic factors. Therefore, phase I and II variant alleles might be useful in evaluating susceptibility to TCa in the studied population.

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Volumen: NA
Editorial: Pharmacogenetics and genomics
Fecha de publicación: 2019
Página de inicio: 1
Página final: 1
Idioma: English
Financiamiento/Sponsor: This work was financed mainly by the Fondecyt grant #1140434, CONICYT, Chile, and in part by Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain (Grant PI15/00303), and Junta de Extremadura, Mérida, Spain (Grant IB16170). Partia
URL: https://journals.lww.com/jpharmacogenetics/pages/default.aspx
Notas: NA