CYP2B66 is associated with increased breast cancer risk

• Published in: International journal of cancer 2014-01, Vol.134 (2), p.426-430
• Main Authors: Justenhoven, Christina, Pentimalli, Daniela, Rabstein, Sylvia, Harth, Volker, Lotz, Anne, Pesch, Beate, Brüning, Thomas, Dörk, Thilo, Schürmann, Peter, Bogdanova, Natalia, Park‐Simon, Tjoung‐Won, Couch, Fergus J., Olson, Janet E., Fasching, Peter A., Beckmann, Matthias W., Häberle, Lothar, Ekici, Arif, Hall, Per, Czene, Kamilla, Liu, Janjun, Li, Jingmei, Baisch, Christian, Hamann, Ute, Ko, Yon‐Dschun, Brauch, Hiltrud
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Biomarkers, Tumor - genetics; Breast cancer; breast cancer risk; Breast Neoplasms - etiology; Cancer; Case-Control Studies; CYP2B6; Cytochrome P-450 CYP2B6; Enzymes; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical research; Medical sciences; Medicin och hälsovetenskap; Meta-Analysis as Topic; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); polymorphism; Polymorphism, Genetic - genetics; Prognosis; Risk Factors; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; testosterone; Tumors; Women
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.28356

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. What's new? A multistage study of more than 8,000 breast cancer cases and controls suggested that the CYP2B6*6 allele, which influences CYP2B6 activity, is associated with an increased risk of breast cancer. This finding adds CYP2B6 to the candidate genes for the evolving panel of known breast cancer susceptibility loci and implicates CYP2B6 in the mechanism by which steroid hormone levels influence breast cancer risk.