17 is associated with decreased breast cancer risk

Christina Justenhoven (1, 2) , Ute Hamann (3) , Christiane B. Pierl (4) , Christian Baisch (5) , Volker Harth (6) , Sylvia Rabstein (6) , Anne Spickenheuer (6) , Beate Pesch (6) , Thomas Brüning (6) , Stefan Winter (1, 2, 7) , Yon-Dschun Ko (5) , Hiltrud Brauch (1, 2)

1 Molecular Mechanisms of Origin and Treatment of Breast Cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
2 Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen
3 Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ)
4 Institute for Occupational Epidemiology and Risk Assessment (IERA), EVONIK Industries
5 Department of Internal Medicine
6 BGFA Forschungsinstitut für Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung
7 Department of Mathematics

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 namely *2 (CY_681_G>A, rs4244285), *3 (_636_G>A, rs57081121) and *17 (_-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 *17 allele (OR 0.77, 95% CI: 0.65–0.93;  = 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 *17 allele (OR 0.57, 95% CI: 0.39–0.83;  = 0.003). Since *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.

Mots clés: CYP2C19; Polymorphisms; Breast cancer; Hormone therapy

Christina Justenhoven, Ute Hamann, Christiane B. Pierl, Christian Baisch, Volker Harth, et al.. 17 is associated with decreased breast cancer risk. Breast Cancer Research and Treatment, 2008, 115 (2), pp.391-396. ⟨10.1007/s10549-008-0076-4⟩. ⟨hal-00478236⟩