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 C. Skaar; Yan Jin

doi:10.1007/s10549-008-0264-2

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 C. Skaar, Yan Jin

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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 language	English (US)
Pages (from-to)	643-650
Number of pages	8
Journal	Breast Cancer Research and Treatment
Volume	115
Issue number	3
DOIs	https://doi.org/10.1007/s10549-008-0264-2
State	Published - Jun 2009

Bibliographical note

Funding Information:
Acknowledgments This study was supported in part by Marshfield Clinic Research Foundation Disease Specific Restricted Funds. We thank Marshfield Clinic Research Foundation for its support through the assistance of Alice Stargardt in the preparation of this manuscript.

Keywords

Breast cancer
Estrogen receptors
PvuII
Tamoxifen
Thromboembolization
XbaI

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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 Skaar, {Todd C.} and Yan Jin",

note = "Funding Information: Acknowledgments This study was supported in part by Marshfield Clinic Research Foundation Disease Specific Restricted Funds. We thank Marshfield Clinic Research Foundation for its support through the assistance of Alice Stargardt in the preparation of this manuscript.",

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doi = "10.1007/s10549-008-0264-2",

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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 C.

AU - Jin, Yan

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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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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