The frameshift polymorphism CYP3A43-74-delA is associated with poor differentiation of breast tumors

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. Cancer 2010. © 2010 American Cancer Society. CYP3A43 is involved in the metabolism of steroid hormones. The authors observed an association between the CYP3A43 74 del A polymorphism and grade of breast tumors (odds ratio, 1.74; Ptrend =.012). The variant allele may lead to increased steroid hormone levels promoting growth of tumor cells and hinder differentiation. Copyright © 2010 American Cancer Society.