CYP2B6*6 is associated with increased breast cancer risk
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CYP2B6*6 is associated with increased breast cancer risk. / 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.
In: INT J CANCER, Vol. 134, No. 2, 15.01.2015, p. 426-30.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CYP2B6*6 is associated with increased breast cancer risk
AU - Justenhoven, Christina
AU - Pentimalli, Daniela
AU - Rabstein, Sylvia
AU - Harth, Volker
AU - Lotz, Anne
AU - Pesch, Beate
AU - Brüning, Thomas
AU - Dörk, Thilo
AU - Schürmann, Peter
AU - Bogdanova, Natalia
AU - Park-Simon, Tjoung-Won
AU - Couch, Fergus J
AU - Olson, Janet E
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Häberle, Lothar
AU - Ekici, Arif
AU - Hall, Per
AU - Czene, Kamilla
AU - Liu, Janjun
AU - Li, Jingmei
AU - Baisch, Christian
AU - Hamann, Ute
AU - Ko, Yon-Dschun
AU - Brauch, Hiltrud
N1 - © 2013 UICC.
PY - 2015/1/15
Y1 - 2015/1/15
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aryl Hydrocarbon Hydroxylases
KW - Breast Neoplasms
KW - Case-Control Studies
KW - Female
KW - Follow-Up Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Meta-Analysis as Topic
KW - Middle Aged
KW - Polymorphism, Genetic
KW - Prognosis
KW - Risk Factors
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
KW - Tumor Markers, Biological
U2 - 10.1002/ijc.28356
DO - 10.1002/ijc.28356
M3 - SCORING: Journal article
C2 - 23824676
VL - 134
SP - 426
EP - 430
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 2
ER -