Association of CYP1A1, CYP1B1 and CYP17 gene polymorphisms and organochlorine pesticides with benign prostatic hyperplasia

Chemosphere. 2014 Aug:108:40-5. doi: 10.1016/j.chemosphere.2014.02.081. Epub 2014 Apr 9.

Abstract

It is well established that steroidal hormones (testosterone and estrogen) increase benign prostatic hyperplasia (BPH) risk. Cytochrome P450 (CYP) enzymes especially CYP1A1, CYP1B1 and CYP17 metabolize these hormones. Apart from that, several endocrine disrupting organochlorine pesticides (OCPs) are reported to mimic the activity of these steroidal hormones. Therefore, functional polymorphisms in these genes and exposure to such pesticides may increase BPH risk further. Our study included 100 newly diagnosed BPH subjects and 100 age-matched healthy male controls. CYP1A1, CYP1B1 and CYP17 polymorphisms were studied using PCR-RFLP and allele-specific PCR method. OCP levels in blood were analyzed by gas chromatography (GC). Levels of p,p'-DDE and endosulfan α were found to be significantly higher amongst BPH subjects as compared to controls (p-values=0.001 and 0.03 respectively) and CYP17 polymorphism was observed to be significantly associated with BPH subjects as compared to controls (p-values=0.03), indicating that these factors may be important risk factors for BPH. However, further studies are required before unequivocal conclusion.

Keywords: Benign prostatic hyperplasia; Cytochrome P450; Organochlorine pesticides; Polymorphism.

MeSH terms

  • Aged
  • Alleles
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP1A1 / genetics*
  • Cytochrome P-450 CYP1B1
  • Dichlorodiphenyl Dichloroethylene / blood
  • Dichlorodiphenyl Dichloroethylene / toxicity*
  • Endosulfan / blood
  • Endosulfan / toxicity*
  • Humans
  • Male
  • Middle Aged
  • Pesticides / blood
  • Pesticides / toxicity*
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Prostatic Hyperplasia / blood
  • Prostatic Hyperplasia / etiology
  • Prostatic Hyperplasia / genetics*
  • Risk Factors
  • Steroid 17-alpha-Hydroxylase / genetics*

Substances

  • Pesticides
  • Dichlorodiphenyl Dichloroethylene
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1B1
  • Steroid 17-alpha-Hydroxylase
  • Endosulfan