title: The PXR rs7643645 polymorphism is associated with the risk of higher prostate-specific antigen levels in prostate cancer patients.
abstract: Levels of enzymes that determine testosterone catabolism such as CYP3A4 have been associated with prostate cancer (PCa) risk. Although some studies have related CYP3A4*1B allele, a gene polymorphism that modifies CYP3A4 expression level, with PCa risk, others have failed, suggesting that additional genetic variants may be involved. Expression of CYP3A4 is largely due to the activation of Pregnane X Receptor (PXR). Particularly, rs2472677 and rs7643645 PXR polymorphisms modify CYP3A4 expression levels. To evaluate whether PXR-HNF3β/T (rs2472677), PXR-HNF4/G (rs7643645), and CYP3A4*1B (rs2740574) polymorphisms are associated with PCa a case control-study was performed. The multiple testing analysis showed that the PXR-HNF4/G polymorphism was associated with higher levels of prostate-specific antigen (PSA) in patients with PCa (OR = 3.99, p = 0.03). This association was stronger in patients diagnosed at the age of 65 years or older (OR = 10.8, p = 0.006). Although the CYP3A4*1B/*1B genotype was overrepresented in PCa patients, no differences were observed in the frequency of this and PXR-HNF3β/T alleles between controls and cases. Moreover, no significant association was found between these polymorphisms and PSA, Gleason grade, or tumor lymph node metastasis.
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, México, D.F., México.
authors.forename: Octavio D
authors.initials: OD
authors.lastname: Reyes-Hernández
authors.affiliation: Departamento de Toxicología, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., México.
authors.forename: Libia
authors.initials: L
authors.lastname: Vega
authors.affiliation: Departamento de Urología, Instituto Nacional de Cancerología, México, D.F., México.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Jiménez-Ríos
authors.affiliation: Departamento de Urología, Instituto Nacional de Cancerología, México, D.F., México.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Martínez-Cervera
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, México, D.F., México.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Lugo-García
authors.affiliation: Departamento de Salud Ambiental, Instituto Nacional de Salud Pública, México, D.F., México.
authors.forename: Leticia
authors.initials: L
authors.lastname: Hernández-Cadena
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ostrosky-Wegman
authors.affiliation: Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, México, D.F., México.
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., México.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Elizondo
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D011987:Receptors, Steroid / Q000235:genetics*; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D051544:Cytochrome P-450 CYP3A; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen