CYP2B6*6 is associated with increased breast cancer risk

Christina Justenhoven, Daniela Pentimalli, Sylvia Rabstein, Volker Harth, Anne Lotz, Beate Pesch, Thomas Brüning, Thilo Dörk, Peter Schürmann, Natalia Bogdanova, Tjoung Won Park-Simon, Fergus J. Couch, Janet E. Olson, Peter A. Fasching, Matthias W. Beckmann, Lothar Häberle, Arif Ekici, Per Hall, Kamilla Czene, Janjun LiuJingmei Li, Christian Baisch, Ute Hamann, Yon Dschun Ko, Hiltrud Brauch

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6-516-G>T (rs3745274) and CYP2B6-785-A>G (rs2279343) and breast cancer risk, we established a specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay. The GENICA breast cancer case-control study showed associations between the variant genotypes CYP2B6-516-TT and CYP2B6-785-GG and breast cancer risk with odds ratios (ORs) of 1.34 (p = 0.001) and 1.31 (p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6-516-T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6-516-G and the CYP2B6-785-G variant had an increased breast cancer risk with ORs of 1.10 (p = 0.027) and 1.10 (p = 0.031), respectively. We conclude that the genetic variants CYP2B6-516-G and CYP2B6-785-G (designated CYP2B6 6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk.

Original languageEnglish (US)
Pages (from-to)426-430
Number of pages5
JournalInternational Journal of Cancer
Volume134
Issue number2
DOIs
StatePublished - Jan 15 2014

Keywords

  • CYP2B6
  • breast cancer risk
  • polymorphism
  • testosterone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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