The frameshift polymorphism CYP3A43_74_delA is associated with poor differentiation of breast tumors

Cancer. 2010 Dec 1;116(23):5358-64. doi: 10.1002/cncr.25508. Epub 2010 Aug 16.

Abstract

Background: CYP3A enzymes, due to their role in the metabolism of steroid hormones, are suggested to affect carcinogenesis of hormone-related cancers. The purpose of the present study was to evaluate the association between polymorphisms located in CYP3A43, breast cancer risk, and tumor characteristics.

Methods: A 3-plex matrix-assisted laser desorption ionization time of flight mass spectrometry assay has been established for CYP3A43_74_delA (CYP3A43*2A), CYP3A43_1018_C>G (CYP3A43*3), and CYP3A43_1047_C>T (CYP3A43*1B) polymorphisms, and 1021 breast cancer cases and 1015 age-matched, population-based controls from the German GENICA collection have been genotyped.

Results: No differences in genotype frequencies between cases and controls were observed, indicating that CYP3A43_74_delA is not associated with breast cancer risk. Subgroup analyses showed an association between the CYP3A43_74_delA allele and high-grade tumors (odds ratio, 1.74; 95% confidence interval, 1.14-2.65 [P=.010 and Ptrend=.012]).

Conclusions: The data support the notion that the CYP3A43_74_delA variant may result in decreased protein and/or activity levels, and this may further lead to increased hormone levels to promote tumor cell growth and hinder differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • Female
  • Genotype
  • Humans
  • Polymorphism, Genetic
  • Risk Factors
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Aryl Hydrocarbon Hydroxylases
  • CYP3A43 protein, human