Role of Estradiol Metabolism and CYP1A1 Polymorphisms in Breast Cancer Risk
| Autor: | Seymour Garte, H. L. Bradlow, Osborne Mp, Trachman J, Emanuela Taioli, Daniel W. Sepkovic, Samantha Garbers, Ganguly S |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Hydroxyestrones Indoles Genotype medicine.medical_treatment Black People Breast Neoplasms White People Steroid Hydroxylation chemistry.chemical_compound Breast cancer Risk Factors Internal medicine Cytochrome P-450 CYP1A1 Humans Medicine Inducer RNA Messenger Polymorphism Genetic Estradiol business.industry Estrogen Antagonists Biological activity Odds ratio Metabolism Middle Aged medicine.disease Confidence interval Gene Expression Regulation Neoplastic Endocrinology chemistry Case-Control Studies Female business |
| Zdroj: | Cancer Detection Prevention. 23:232-237 |
| ISSN: | 1525-1500 0361-090X |
| Popis: | The endogenous metabolism of estrogens is primarily oxidative and involves hydroxylation of the steroid at either C2 (2-OHE1) or C16 (16-OHE1). While the 2-OHE1 metabolites are essentially devoid of peripheral biological activity, 16-OHE1 is an estrogen agonist. There is evidence of an association between the 2-OHE1/16-OHE1 metabolites ratio and breast cancer risk. The CYP1A1 gene may play a role in the 2-hydroxylation (2-OH) of estradiol. African-American women with the wild-type CYP1A1 gene showed a significant increase in the 2-OHE1/16-OHE1 ratio, from 1.35 +/- 0.56 at baseline to 2.39 +/- 0.98 (p = 0.006) after 5 days of treatment with indole-3-carbinol (400 mg/day), a 2-OHE1 inducer. Women with the Msp1 polymorphism showed no significant increase, (0.37% +/- 0.17%). In a case-control study involving 57 women with breast cancer and 312 female controls, the frequency of the homozygous Msp1 polymorphism was 4.2% in African-American controls and 16% in African-American breast cancer cases. The odds ratio of breast cancer with the Msp1 homozygous variant was 8.4 (95% confidence interval: 1.7-41.7). This association was not observed in Caucasian women. The other CYP1A1 polymorphisms were not associated with breast cancer. The CYP1A1 Msp1 polymorphism may be a marker of altered estradiol metabolism and of increased susceptibility to estrogen-related breast cancer in African-Americans. |
| Databáze: | OpenAIRE |
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