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Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
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Published on: May 29, 2019

Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base excision repair genes and prostate

Nora L Nock1, Mine S Cicek, Li Li

  • 1Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.

Carcinogenesis
|March 30, 2006
PubMed

Insights

Genetic variations in COMT, hOGG1, and CYP1B1 influence prostate cancer risk. The hOGG1 326 Cys/Cys genotype is linked to reduced risk in aggressive prostate cancer, especially with specific CYP1B1 and XRCC1 genotypes.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Hormones' role in prostate cancer often focuses on receptor pathways.
  • Catechol estrogens can generate reactive oxygen species (ROS) if not inactivated by catechol-O-methyltransferase (COMT).
  • ROS can cause DNA damage, potentially leading to mutations if not repaired by base excision repair (BER) systems.

Purpose of the Study:

  • To investigate non-receptor-mediated estrogen effects on prostate cancer risk.
  • To evaluate the association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate cancer.
  • To explore gene-environment interactions in prostate cancer development.

Main Methods:

  • A family-based case-control study was conducted with 439 prostate cancer cases and 479 brother controls.
  • Genotyping for COMT Val158Met, hOGG1 Ser326Cys, CYP1B1 432, and XRCC1 399 polymorphisms was performed.
  • Statistical analyses assessed the association between genotypes and prostate cancer risk, including interactions.

Main Results:

  • No significant association was found between COMT or hOGG1 polymorphisms and overall prostate cancer risk.
  • The hOGG1 326 Cys/Cys genotype showed an inverse association with aggressive prostate cancer (OR=0.30).
  • Combinations of specific genotypes (CYP1B1, hOGG1, XRCC1) further reduced aggressive prostate cancer risk in Caucasians (OR=0.09).

Conclusions:

  • The hOGG1 326 Cys/Cys genotype may play a protective role against aggressive prostate cancer.
  • Gene-environment interactions involving ROS-generating pathways and DNA repair mechanisms are important in aggressive prostate cancer.
  • These findings suggest non-receptor-mediated estrogen effects contribute to prostate cancer pathogenesis.

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