Genetic variants in xenobiotic detoxification enzymes, antioxidant defenses and hormonal pathways as biomarkers of susceptibility to prostate cancer

• Published in: The Science of the total environment Vol. 730; p. 138314
• Main Authors: Martinez-Gonzalez, L.J., Antúnez-Rodríguez, A., Vazquez-Alonso, F., Hernandez, A.F., Alvarez-Cubero, M.J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2020
• Subjects: Antioxidant enzymes; antioxidants; biomarkers; biopsy; Chemical exposures; environment; estrogens; oxidative stress; Physical activity; Prostate cancer; prostate-specific antigen; prostatic neoplasms; questionnaires; risk reduction; tobacco; xenobiotics; O2; Physical activity; PON1; H; CNV; H2O2; L; CYP17A1; PCa; TNM; APMAP; SNP; GSH; PSA; Chemical exposures; GSSG; OR; CI; TXNRD1; Antioxidant enzymes; G6PDH; GST; SOD; EPS15R; GR; EDTA; EMT; ESR1; GPx; AR; XME; NA; PRDX; ETC; NAT2; NOX; CAT; ROS; LD; LH; vs; Prostate cancer; LOOH
• ISSN: 0048-9697; 1879-1026; 1879-1026
• DOI: 10.1016/j.scitotenv.2020.138314

Cancer is considered a complex disease that in many cases results from the interaction between chemical exposures, either from environmental or dietary sources, and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) or antioxidant enzymatic defenses. This study explored associations and interactions between genetic and environmental risk factors on the risk of prostate cancer (PCa) in 323 subjects that underwent prostate biopsy due to prostate specific antigen (PSA) levels above 4 ng/ml (161 PCa and 162 non-PCa). Eleven genes involved directly or indirectly in xenobiotic detoxification, oxidative stress and estrogen signaling were studied (GSTM1, GPX1 (rs1050450 and rs17650792), NAT2 (rs1801280), TXNRD1 (rs7310505), PRDX3 (rs3740562), CYP17A1 (rs743572), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), and ESR1 (rs746432)). A structured questionnaire was administered to all individuals to assess environmental and dietary chemical exposures. Medical data was collected by urologists. GPX1 rs17650792 polymorphism was the only one showing a significant inverse association with PCa risk. PRDX3 and GPX1 (rs17650792) genetic polymorphisms were significantly associated with Gleason score and PSA levels, respectively. The intake of nuts and soya products was associated with a reduced risk of PCa, as well as the performance of physical activity. Moreover, a number of gene-environmental interactions were found to increase the risk of PCa, particularly exposure to pesticides and rs1801280 (NAT2) and tobacco smoking and rs1050450 (GPX1). These findings suggest that the association of genetic and environmental risk factors with PCa risk should be assessed jointly for a better understanding of this complex disease. [Display omitted] •Xenobiotic-metabolizing enzymes play a relevant role in hormonal tumors.•Dietary and environmental factors are linked with a higher risk of prostate cancer.•ROS generation and impaired enzymatic antioxidant mechanisms may lead to DNA damage.