Media type: E-Article Title: The frameshift polymorphism CYP3A43_74_delA is associated with poor differentiation of breast tumors Contributor: Justenhoven, Christina; Winter, Stefan; Hamann, Ute; Haas, Susanne; Fischer, Hans‐Peter; Pesch, Beate; Brüning, Thomas; Ko, Yon‐Dschun; Brauch, Hiltrud Published: Wiley, 2010 Published in: Cancer, 116 (2010) 23, Seite 5358-5364 Language: English DOI: 10.1002/cncr.25508 ISSN: 0008-543X; 1097-0142 Origination: Footnote: Description: AbstractBACKGROUND: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. Cancer 2010. © 2010 American Cancer Society. Access State: Open Access