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

Roco, Angelaa,,f; Lavanderos, Alejandraa; Cayún, Juan P.a; Acevedo, Cristiana,,e; Celedón, Cesara; Rubilar, Juan C.a; Sandoval, Christophera; Cerpa, Lesliea; García-Martín, Elenab; Agúndez, Jose A.b; Esguevillas, Garab; Amo, Gemmab; Canepa, Angelod; Cerda, Bertac; Peña, Karinad; Cáceres, Dante D.a,,g,,h; Varela, Nelson M.a; Quiñones, Luis A.a

doi: 10.1097/FPC.0000000000000379
Original Articles
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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.

aLaboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile

bDepartment of Pharmacology, University of Extremadura. ARADyAL Instituto de Salud Carlos III, Cáceres. Spain

cNational Cancer Institute

dSan Juan de Dios Hospital

eUniversity of Chile Clinical Hospital

fFaculty of Life Sciences, Andrés Bello University

gInstitute of Population Health, Faculty of Medicine, University of Chile Santiago

hFaculty of Life Sciences, University of Tarapaca, Arica, Chile

Received 12 June 2018 Accepted 19 November 2018

Correspondence to Luis A. Quiñones, PhD, Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic-Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Carlos Shachtebeck 299, Quinta Normal, Santiago 8500000, Chile Tel: + 56 229 770 741/+ 56 2977 0744; e-mail: lquinone@med.uchile.cl

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