CYP2C19*17 is associated with decreased breast cancer risk.
Cytochrome P450 2C19 (CYP2C19) plays an important role in the metabolism of xenobiotics and drugs and contributes to the catabolism of endogenous substrates like estradiol. Genetic variability impacts expression and activity of CYP2C19 and therefore can influence catabolism of estrogens. In the present study we analyzed the association of three polymorphisms of CYP2C19 namely CYP2C19*2 (CYP2C19_681_G>A, rs4244285), CYP2C19*3 (CYP2C19_636_G>A, rs57081121) and CYP2C19*17 (CYP2C19_-806_C>T, rs12248560), with breast cancer susceptibility. We genotyped 1,015 breast cancer cases and 1,021 age-matched, population-based controls of the German GENICA study by matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Risk estimates were calculated by logistic regression. All tests were two-sided. We observed a decreased breast cancer risk for carriers of the CYP2C19*17 allele (OR 0.77, 95% CI: 0.65-0.93; P = 0.005). In subgroup analysis we observed a significant decreased breast cancer risk for women using hormone therapy for ten years or longer who were carriers of the CYP2C19*17 allele (OR 0.57, 95% CI: 0.39-0.83; P = 0.003). Since CYP2C19*17 defines an ultra rapid metabolizer phenotype we suggest that an increased catabolism of estrogens by CYP2C19 may lead to decreased estrogen levels and therefore reduces breast cancer risk. This protective effect seems to be stronger in combination with long-term intake of supplemental estrogens during hormone therapy.
Molecular Mechanisms of Origin and Treatment of Breast Cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
Christina
C
Justenhoven
Ute
U
Hamann
Christiane B
CB
Pierl
Christian
C
Baisch
Volker
V
Harth
Sylvia
S
Rabstein
Anne
A
Spickenheuer
Beate
B
Pesch
Thomas
T
Brüning
Stefan
S
Winter
Yon-Dschun
YD
Ko
Hiltrud
H
Brauch
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19