Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients

April N. Tucker, Katherine A. Tkaczuk, Lynn M. Lewis, Dragana Tomic, Chang K. Lim, Jodi A. Flaws

Research output: Contribution to journalArticle

Abstract

Tamoxifen (TAM) is widely used for treatment and prevention of breast cancer. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP3A5. Although two genetic polymorphisms in CYP3A5 are known (CYP3A5*3 and CYP3A5*6), the effects of these polymorphisms on TAM metabolism, TAM side effects, and tumor characteristics are unknown. Thus, this work tested the hypothesis that CYP3A5 polymorphisms are associated with differential TAM levels, TAM side effects, and tumor characteristics in breast cancer patients. Postmenopausal women with breast cancer (n=98) were recruited from a single cancer center. Polymorphic status was established using polymerase chain reactions (PCR). The associations between polymorphic status, race, TAM levels, side effects, and tumor characteristics were assessed using t-tests and logistic regression models. The data indicate that 40.7% of the breast cancer patients had the CYP3A5*3 polymorphism, and 9.1% had the CYP3A5*6 polymorphism. In addition, Caucasian women were 26 times more likely to carry the CYP3A5*3 polymorphism than African American (AA) women, whereas AA women were nine times more likely to carry the CYP3A5*6 polymorphism than Caucasian women. No significant differences were seen in TAM or TAM metabolite levels or TAM side effects by polymorphic status. There was a significant difference, however, in mean tumor size in women with the CYP3A5*6 polymorphism (3.6±0.98 cm) compared to those without the polymorphism (2.0±0.18 cm) (P

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalCancer Letters
Volume217
Issue number1
DOIs
StatePublished - Jan 10 2005
Externally publishedYes

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Tamoxifen
Cytochromes
Breast Neoplasms
Neoplasms
African Americans
Cytochrome P-450 Enzyme System
Logistic Models
Genetic Polymorphisms
Polymerase Chain Reaction

Keywords

  • Breast cancer
  • Cytochrome P450 3A5
  • Metabolism
  • Polymorphisms
  • Race/ethnicity
  • Tamoxifen

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. / Tucker, April N.; Tkaczuk, Katherine A.; Lewis, Lynn M.; Tomic, Dragana; Lim, Chang K.; Flaws, Jodi A.

In: Cancer Letters, Vol. 217, No. 1, 10.01.2005, p. 61-72.

Research output: Contribution to journalArticle

Tucker, April N. ; Tkaczuk, Katherine A. ; Lewis, Lynn M. ; Tomic, Dragana ; Lim, Chang K. ; Flaws, Jodi A. / Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. In: Cancer Letters. 2005 ; Vol. 217, No. 1. pp. 61-72.
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abstract = "Tamoxifen (TAM) is widely used for treatment and prevention of breast cancer. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP3A5. Although two genetic polymorphisms in CYP3A5 are known (CYP3A5*3 and CYP3A5*6), the effects of these polymorphisms on TAM metabolism, TAM side effects, and tumor characteristics are unknown. Thus, this work tested the hypothesis that CYP3A5 polymorphisms are associated with differential TAM levels, TAM side effects, and tumor characteristics in breast cancer patients. Postmenopausal women with breast cancer (n=98) were recruited from a single cancer center. Polymorphic status was established using polymerase chain reactions (PCR). The associations between polymorphic status, race, TAM levels, side effects, and tumor characteristics were assessed using t-tests and logistic regression models. The data indicate that 40.7{\%} of the breast cancer patients had the CYP3A5*3 polymorphism, and 9.1{\%} had the CYP3A5*6 polymorphism. In addition, Caucasian women were 26 times more likely to carry the CYP3A5*3 polymorphism than African American (AA) women, whereas AA women were nine times more likely to carry the CYP3A5*6 polymorphism than Caucasian women. No significant differences were seen in TAM or TAM metabolite levels or TAM side effects by polymorphic status. There was a significant difference, however, in mean tumor size in women with the CYP3A5*6 polymorphism (3.6±0.98 cm) compared to those without the polymorphism (2.0±0.18 cm) (P",
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AU - Lim, Chang K.

AU - Flaws, Jodi A.

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