title: CYP17 genotype modifies the association between lignan supply and premenopausal breast cancer risk in humans.
abstract: Cytochrome P450c17alpha (CYP17) has been associated with alterations in steroid hormone levels and premenopausal breast cancer risk and could modify the association between phytoestrogen intake and breast cancer risk. We examined plasma concentrations of enterolactone and genistein, estimated dietary phytoestrogen intake, CYP17 5'-UTR MspA1 genetic polymorphism, and breast cancer risk in 267 premenopausal breast cancer patients and 573 age-matched population controls from Germany. Multivariate logistic regression was used to estimate breast cancer risk associated with quartiles of phytoestrogen intake by genotype and to investigate gene-nutrient interactions. Premenopausal breast cancer risk was not significantly associated with the CYP17 A2 genotype. We observed a significant modifying effect of CYP17 genotype on plasma enterolactone-associated breast cancer risk (P for interaction < 0.01). Plasma enterolactone was significantly inversely related to breast cancer risk only in A2A2 carriers, showing odds ratios and 95% CI of 0.02 (0.00-0.41) and 0.01 (0.00-0.21) for the third and fourth quartiles vs. the lowest quartile, respectively. This inverse association was also found for the calculated enterolignan production as well as matairesinol intake. Compared with A1A1 carriers with the lowest enterolactone supply, the risk reduction associated with a high enterolactone supply resulted in a comparably decreased breast cancer risk for all genotypes. For genistein, no clear indication for a differential effect by CYP17 genotype was obtained. Our results suggest that CYP17 genotype modifies the protective effect of lignans on premenopausal breast cancer risk. Women homozygous for A2 allele benefit most from high plasma enterolactone concentrations and a high consumption of dietary precursors.
authors.affiliation: Unit of Human Nutrition and Cancer Prevention, Technical University University of Munich, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Piller
authors.forename: Emaculate
authors.initials: E
authors.lastname: Verla-Tebit
authors.forename: Shan
authors.initials: S
authors.lastname: Wang-Gohrke
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000097:blood; D000328:Adult; D016588:Anticarcinogenic Agents / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D016022:Case-Control Studies; D005260:Female; D019833:Genistein / Q000097:blood*; D005838:Genotype; D005858:Germany; D006801:Humans; D017705:Lignans / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D016015:Logistic Models; D008875:Middle Aged; D017697:Premenopause; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000502:physiology
chemical_list: D016588:Anticarcinogenic Agents; D017705:Lignans; D019833:Genistein; D013254:Steroid 17-alpha-Hydroxylase; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone