Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy

Adedayo A. Onitilo, Catherine A. McCarty, Russell A. Wilke, Ingrid Glurich, Jessica M. Engel, David A. Flockhart, Anne Nguyen, Lang Li, Deming Mi, Todd Skaar, Yan Jin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Research Project, a population-based DNA repository, was tested for association between incidence of tamoxifen-associated thromboembolic events (TTE) and single nucleotide polymorphisms encoding the estrogen receptors 1,2 (ESR1, ESR2) or drug metabolism enzymes cytochrome P450 2D6 (CYP2D6) and aromatase (CYP19). TTE were experienced by 16/220 subjects with risk association noted for XbaI (rs9340799) genotype and ESR1 Xbal/PvuII diplotype (rs9340799 and rs2234693) (hazard ratio 3.47, 95% CI 0.97-12.44, P = 0.035). Association persisted after adjusting for classical risk factors including age at diagnosis and body mass index at enrollment. Initial evidence of association between increased risk for TTE and ESR1 genotype and ESR1 diplotype is presented. Determination of estrogen receptor genotype may identify a subset of women at increased risk for thromboembolism with tamoxifen exposure.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalBreast Cancer Research and Treatment
Volume115
Issue number3
DOIs
StatePublished - Jun 2009

Fingerprint

Venous Thromboembolism
Tamoxifen
Estrogen Receptors
Genotype
Aromatase
Thromboembolism
Therapeutics
Breast Neoplasms
Estrogen Receptor beta
Cytochrome P-450 CYP2D6
Precision Medicine
Estrogen Receptor alpha
DNA
Single Nucleotide Polymorphism
Body Mass Index
Incidence
Enzymes
Research
Pharmaceutical Preparations
Population

Keywords

  • Breast cancer
  • Estrogen receptors
  • PvuII
  • Tamoxifen
  • Thromboembolization
  • XbaI

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Onitilo, A. A., McCarty, C. A., Wilke, R. A., Glurich, I., Engel, J. M., Flockhart, D. A., ... Jin, Y. (2009). Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy. Breast Cancer Research and Treatment, 115(3), 643-650. https://doi.org/10.1007/s10549-008-0264-2

Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy. / Onitilo, Adedayo A.; McCarty, Catherine A.; Wilke, Russell A.; Glurich, Ingrid; Engel, Jessica M.; Flockhart, David A.; Nguyen, Anne; Li, Lang; Mi, Deming; Skaar, Todd; Jin, Yan.

In: Breast Cancer Research and Treatment, Vol. 115, No. 3, 06.2009, p. 643-650.

Research output: Contribution to journalArticle

Onitilo, AA, McCarty, CA, Wilke, RA, Glurich, I, Engel, JM, Flockhart, DA, Nguyen, A, Li, L, Mi, D, Skaar, T & Jin, Y 2009, 'Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy', Breast Cancer Research and Treatment, vol. 115, no. 3, pp. 643-650. https://doi.org/10.1007/s10549-008-0264-2
Onitilo, Adedayo A. ; McCarty, Catherine A. ; Wilke, Russell A. ; Glurich, Ingrid ; Engel, Jessica M. ; Flockhart, David A. ; Nguyen, Anne ; Li, Lang ; Mi, Deming ; Skaar, Todd ; Jin, Yan. / Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy. In: Breast Cancer Research and Treatment. 2009 ; Vol. 115, No. 3. pp. 643-650.
@article{0f9d92288cbb4d7ea9427ec31a39c667,
title = "Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy",
abstract = "Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Research Project, a population-based DNA repository, was tested for association between incidence of tamoxifen-associated thromboembolic events (TTE) and single nucleotide polymorphisms encoding the estrogen receptors 1,2 (ESR1, ESR2) or drug metabolism enzymes cytochrome P450 2D6 (CYP2D6) and aromatase (CYP19). TTE were experienced by 16/220 subjects with risk association noted for XbaI (rs9340799) genotype and ESR1 Xbal/PvuII diplotype (rs9340799 and rs2234693) (hazard ratio 3.47, 95{\%} CI 0.97-12.44, P = 0.035). Association persisted after adjusting for classical risk factors including age at diagnosis and body mass index at enrollment. Initial evidence of association between increased risk for TTE and ESR1 genotype and ESR1 diplotype is presented. Determination of estrogen receptor genotype may identify a subset of women at increased risk for thromboembolism with tamoxifen exposure.",
keywords = "Breast cancer, Estrogen receptors, PvuII, Tamoxifen, Thromboembolization, XbaI",
author = "Onitilo, {Adedayo A.} and McCarty, {Catherine A.} and Wilke, {Russell A.} and Ingrid Glurich and Engel, {Jessica M.} and Flockhart, {David A.} and Anne Nguyen and Lang Li and Deming Mi and Todd Skaar and Yan Jin",
year = "2009",
month = "6",
doi = "10.1007/s10549-008-0264-2",
language = "English",
volume = "115",
pages = "643--650",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy

AU - Onitilo, Adedayo A.

AU - McCarty, Catherine A.

AU - Wilke, Russell A.

AU - Glurich, Ingrid

AU - Engel, Jessica M.

AU - Flockhart, David A.

AU - Nguyen, Anne

AU - Li, Lang

AU - Mi, Deming

AU - Skaar, Todd

AU - Jin, Yan

PY - 2009/6

Y1 - 2009/6

N2 - Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Research Project, a population-based DNA repository, was tested for association between incidence of tamoxifen-associated thromboembolic events (TTE) and single nucleotide polymorphisms encoding the estrogen receptors 1,2 (ESR1, ESR2) or drug metabolism enzymes cytochrome P450 2D6 (CYP2D6) and aromatase (CYP19). TTE were experienced by 16/220 subjects with risk association noted for XbaI (rs9340799) genotype and ESR1 Xbal/PvuII diplotype (rs9340799 and rs2234693) (hazard ratio 3.47, 95% CI 0.97-12.44, P = 0.035). Association persisted after adjusting for classical risk factors including age at diagnosis and body mass index at enrollment. Initial evidence of association between increased risk for TTE and ESR1 genotype and ESR1 diplotype is presented. Determination of estrogen receptor genotype may identify a subset of women at increased risk for thromboembolism with tamoxifen exposure.

AB - Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Research Project, a population-based DNA repository, was tested for association between incidence of tamoxifen-associated thromboembolic events (TTE) and single nucleotide polymorphisms encoding the estrogen receptors 1,2 (ESR1, ESR2) or drug metabolism enzymes cytochrome P450 2D6 (CYP2D6) and aromatase (CYP19). TTE were experienced by 16/220 subjects with risk association noted for XbaI (rs9340799) genotype and ESR1 Xbal/PvuII diplotype (rs9340799 and rs2234693) (hazard ratio 3.47, 95% CI 0.97-12.44, P = 0.035). Association persisted after adjusting for classical risk factors including age at diagnosis and body mass index at enrollment. Initial evidence of association between increased risk for TTE and ESR1 genotype and ESR1 diplotype is presented. Determination of estrogen receptor genotype may identify a subset of women at increased risk for thromboembolism with tamoxifen exposure.

KW - Breast cancer

KW - Estrogen receptors

KW - PvuII

KW - Tamoxifen

KW - Thromboembolization

KW - XbaI

UR - http://www.scopus.com/inward/record.url?scp=67349174180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349174180&partnerID=8YFLogxK

U2 - 10.1007/s10549-008-0264-2

DO - 10.1007/s10549-008-0264-2

M3 - Article

C2 - 19082882

AN - SCOPUS:67349174180

VL - 115

SP - 643

EP - 650

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -