Association of CYP1B1 polymorphisms and breast cancer risk.

Cytochrome P450 1B1 catalyzes the conversion of 17-beta-estradiol (E2) to thecatechol estrogen metabolites 2-OH-E2 and 4-OH-E2 that have been postulated to be involved in mammary carcinogenesis. We sought to determine whether two common functional polymorphisms in Cytochrome P450 1B1, V432L (m1), and A453S (m2) are related to breast cancer risk. Using a nested case control design within the Nurses' Health Study cohort, we genotyped 453 cases and 456 controls and found no significant association between m1[val/leu and leu/leu versus val/val, OR = 1 (CI, 0.72-1.45)] or m2 [asn/ser and ser/ser versus asn/asn, OR = 0.8 (CI, 0.62-1.15)] and breast cancer risk. However, we did observe women with the Val/Val (m1) genotype to have a higher percentage of estrogen receptor-positive tumors (P = 0.03). We did not observe any correlation with the m2 genotypes and estrogen receptor status. The association of the m1 and m2 genotypes on plasma hormone levels in postmenopausal control women not using hormone replacement therapy was also evaluated. Carriers of the m1 leu and m2 ser alleles had modestly higher estradiol levels but similar estrone and estrone sulfate levels. The results presented do not support a strong association between m1 and m2 and the risk of breast cancer.

[1]  L. Kolonel,et al.  Case-control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[2]  N. Roodi,et al.  Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. , 2000, Cancer research.

[3]  J. Liehr,et al.  Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens. , 2000, Cancer research.

[4]  T. Shimada,et al.  Catalytic properties of polymorphic human cytochrome P450 1B1 variants. , 1999, Carcinogenesis.

[5]  W. Willett,et al.  The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer. , 1999, Cancer research.

[6]  N. Roodi,et al.  Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer. , 1998, Cancer research.

[7]  J. Manson,et al.  Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. , 1998, Journal of the National Cancer Institute.

[8]  J A McKay,et al.  Tumor-specific expression of cytochrome P450 CYP1B1. , 1997, Cancer research.

[9]  T. Sutter,et al.  Induction of cytochrome P450 1B1 and catechol estrogen metabolism in ACHN human renal adenocarcinoma cells , 1997, The Journal of Steroid Biochemistry and Molecular Biology.

[10]  N. Walker,et al.  17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Liehr,et al.  4-Hydroxylation of estrogens as marker of human mammary tumors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  W. F. Greenlee,et al.  Expression of cytochrome P450 CYP1B1 in breast cancer , 1995, FEBS letters.

[13]  C. Jefcoate,et al.  The effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on estrogen metabolism in MCF-7 breast cancer cells: Evidence for induction of a novel 17β-estradiol 4-hydroxylase , 1994, The Journal of Steroid Biochemistry and Molecular Biology.

[14]  J. Liehr,et al.  DNA single-strand breaks in kidneys of Syrian hamsters treated with steroidal estrogens: hormone-induced free radical damage preceding renal malignancy. , 1994, Carcinogenesis.

[15]  G. Vollmer,et al.  Catecholestrogens are agonists of estrogen receptor dependent gene expression in MCF-7 cells , 1994, The Journal of Steroid Biochemistry and Molecular Biology.

[16]  G. Vollmer,et al.  Catecholestrogens are MCF-7 cell estrogen receptor agonists , 1993, The Journal of Steroid Biochemistry and Molecular Biology.

[17]  E. Schuetz,et al.  17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA. , 1992, Archives of biochemistry and biophysics.

[18]  Li Jj,et al.  Estrogen carcinogenesis in Syrian hamster tissues: role of metabolism. , 1987 .