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Article first published online: 16 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 23, pages 5358–5364, 1 December 2010
How to Cite
Justenhoven, C., Winter, S., Hamann, U., Haas, S., Fischer, H.-P., Pesch, B., Brüning, T., Ko, Y.-D., Brauch, H. and for the GENICA Network (2010), The frameshift polymorphism CYP3A43_74_delA is associated with poor differentiation of breast tumors. Cancer, 116: 5358–5364. doi: 10.1002/cncr.25508
We thank all women participating in the GENICA study, and interviewers, physicians, and pathologists of the study region for support.
The GENICA Network is comprised of: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart and University Tübingen, Tübingen, Germany (Hiltrud Brauch and Christina Justenhoven); Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany (Ute Hamann); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (Yon-Dschun Ko and Christian Baisch); Institute for Prevention and Occupational Medicine of German Social Accident Insurance, Bochum, Germany (Thomas Brüning, Beate Pesch, Volker Harth, and Sylvia Rabstein); and Institute of Pathology, Medical Faculty of the University of Bonn, Bonn, Germany (Susanne Haas and Hans-Peter Fischer).
- Issue published online: 23 NOV 2010
- Article first published online: 16 AUG 2010
- Manuscript Accepted: 27 MAY 2010
- Manuscript Revised: 5 MAY 2010
- Manuscript Received: 29 MAR 2010
- breast cancer;
- tumor grade
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.
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.
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]).
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.