Postmenopausal estrogen monotherapy-associated breast cancer risk is modified by CYP17A1_-34_T>C polymorphism.
Long-term hormone therapy (HT) is a recognized risk factor for postmenopausal breast cancer. Elevated steroid hormone levels play a critical role in breast carcinogenesis and this may be contributed by the efficiency of hormone biosynthesis. Within this context, genetic polymorphisms related to steroid hormone biosynthesis may modify HT-associated postmenopausal breast cancer risk. CYP17 is a key player of this pathway and the CYP17A1_-34_T > C polymorphism has been suggested to affect breast cancer risk in women using long-term HT. We genotyped 13 polymorphisms of seven genes of the steroid hormone biosynthesis pathway in 3,149 postmenopausal breast cancer patients and 5,489 age-matched controls from Germany. We observed a significant interaction of CYP17A1_-34_T > C and HT use on breast cancer risk in a co-dominant model (P (interaction) = 0.007). Current users of estrogen monotherapy showed a significantly increased risk for duration of use per 5-year increment when they were carriers of the CYP17A1_-34_TC genotype (OR 1.13, 95% CI: 1.04-1.23 per 5 years of use). We conclude that CYP17A1_-34_T > C may be part of the genetic background to contribute to postmenopausal breast cancer risk in women using estrogen monotherapy.
christina.justenhoven@ikp-stuttgart.de
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000368:Aged; D001141:Aromatase / Q000235:genetics; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000235:genetics; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000502:physiology
D006913:Hydroxysteroid Dehydrogenases; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human