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.
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.
Authors: Eva J Brandl; Nabilah I Chowdhury; Arun K Tiwari; Tristram A P Lett; Herbert Y Meltzer; James L Kennedy; Daniel J Müller Journal: J Neural Transm (Vienna) Date: 2014-08-24 Impact factor: 3.575
Authors: Christina Justenhoven; Ofure Obazee; Stefan Winter; Sylvia Rabstein; Anne Lotz; Volker Harth; Beate Pesch; Thomas Brüning; Christian Baisch; Jaana M Hartikainen; Arto Mannermaa; Veli-Matti Kosma; Vesa Kataja; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Peter A Fasching; Matthias Beckmann; Arif B Ekici; Alexander Hein; Per Hall; Jingmei Li; Jenny Chang-Claude; Dieter Flesch-Janys; Petra Seibold; Anja Rudolph; Ute Hamann; Yon-Dschun Ko; Hiltrud Brauch Journal: Front Genet Date: 2013-06-11 Impact factor: 4.599