Abstract

Studies in Caucasian women have shown that the formation of estrogen-DNA adducts is greater in women at high risk for breast cancer or already diagnosed with the disease. To begin investigating whether the role of estrogens in the etiology of breast cancer is similar in African-American (AA) women, a saliva sample and a spot urine sample were collected from 19 AA women with breast cancer and 23 AA women not diagnosed with breast cancer. In the urine samples, 20 estrogen metabolites, conjugates, and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry, and then the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and estrogen conjugates was significantly greater in cases compared to controls (92.4 ± 46.4 vs 38.5 ± 18.9, p < 0.0001). From the saliva samples, genomic DNA was purified and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes, catechol-O-methyltransferase (rs4680) and cytochrome P450 1B1 (rs1056836). There was no association between rs4680 and rs1056836 genotypes and adduct ratios or breast cancer status. This pilot study found higher DNA adduct ratios in women with breast cancer, which suggests that estrogen metabolism is out of balance, and the formation of estrogen-DNA adducts may exert a critical role in breast cancer initiation in AA women.

Original languageEnglish (US)
Pages (from-to)190-194
Number of pages5
JournalChemical Research in Toxicology
Volume32
Issue number1
DOIs
StatePublished - Jan 22 2019

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Metabolism
African Americans
Estrogens
Breast Neoplasms
DNA Adducts
Metabolites
Saliva
Urine
Catechol O-Methyltransferase
Liquid chromatography
Genetic Polymorphisms
Tandem Mass Spectrometry
Polymorphism
Liquid Chromatography
Cytochrome P-450 Enzyme System
Mass spectrometry
Genes
Genotype
Association reactions
DNA

ASJC Scopus subject areas

  • Toxicology

Cite this

Estrogen Metabolism in African-American Women with and without Breast Cancer : A Pilot Study. / Zahid, Muhammad; Mondal, Bodhisattwa; LeVan, Tricia D; Rogan, Eleanor G.

In: Chemical Research in Toxicology, Vol. 32, No. 1, 22.01.2019, p. 190-194.

Research output: Contribution to journalArticle

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