Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis

AD Kjaergaard; C Ellervik; A Tybjaerg-Hansen; CK Axelsson; ML Grønholdt; P Grande; Gorm B Jensen; BG Nordestgaard; Anne Tybjaerg-Hansen; Alisa D Kjaergaard; Christina Ellervik; Christen Kirk Axelsson; Marie-Louise Grønholdt; Peer Grande; Børge G Nordestgaard

doi:http://dx.doi.org/10.1161/CIRCULATIONAHA.106.615567

Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis

AD Kjaergaard, C Ellervik, A Tybjaerg-Hansen, CK Axelsson, ML Grønholdt, P Grande, Gorm B Jensen, BG Nordestgaard, Anne Tybjaerg-Hansen, Alisa D Kjaergaard, Christina Ellervik, Christen Kirk Axelsson, Marie-Louise Grønholdt, Peer Grande, Børge G Nordestgaard

76 Citations (Scopus)

Abstract

Background- We hypothesized that the estrogen receptor ${alpha}$ (ESR1) IVS1-397T/C polymorphism affects high-density lipoproteincholesterol response to hormone replacement therapy and riskof cardiovascular disease (CVD), cancer of reproductive organs,and hip fracture.

Methods and Results- We studied cross-sectionally 9244individuals from the Danish general population and followedthem up for 23 to 25 years. End points were CVD (ischemic heartdisease, myocardial infarction, angina pectoris, ischemic cerebrovasculardisease, ischemic stroke, other ischemic cerebrovascular disease,venous thromboembolism, deep vein thrombosis, and pulmonaryembolism), cancer of reproductive organs (breasts, ovaries,uterus, and prostate), and hip fracture. We also studied patientswith ischemic heart disease (n=2495), ischemic cerebrovasculardisease (n=856), and breast cancer (n=1256) versus general populationcontrols. The CC, CT, and TT genotypes had general populationfrequencies of 21%, 50%, and 29%, respectively. Cross-sectionally,genotype did not influence high-density lipoprotein cholesterolresponse to hormone replacement therapy. In the cohort study,there were no differences in risks of CVD, cancer of reproductiveorgans, or hip fracture between genotypes. In case-controlstudies, risk of CVD did not differ between genotypes; however,the odds ratio for breast cancer in women with TT versus CCgenotypes was 1.4 (95% CI, 1.1 to 1.7). Meta-analysis in menof 6 previous and the present 2 studies, including 4799 casesand 12 190 controls, showed odds ratios in CC versus CT andTT genotypes for fatal and nonfatal myocardial infarction of0.81 (95% CI, 0.59 to 1.12) and 1.08 (95% CI, 0.97 to 1.21).

Conclusions- ESR1 IVS1-397T/C polymorphism does not influencehigh-density lipoprotein cholesterol response to hormone replacementtherapy or risk of CVD, most cancers of reproductive organs,or hip fracture

Original language	English
Journal	Circulation
Volume	115
Issue number	7
Pages (from-to)	861-71
Number of pages	11
ISSN	0009-7322
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.106.615567
Publication status	Published - 2007

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http://circ.ahajournals.org/cgi/content/full/115/7/861

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Kjaergaard, AD., Ellervik, C., Tybjaerg-Hansen, A., Axelsson, CK., Grønholdt, ML., Grande, P., Jensen, G. B., Nordestgaard, BG., Tybjaerg-Hansen, A., Kjaergaard, A. D., Ellervik, C., Axelsson, C. K., Grønholdt, M-L., Grande, P., & Nordestgaard, B. G. (2007). Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis. Circulation, 115(7), 861-71. https://doi.org/10.1161/CIRCULATIONAHA.106.615567

Kjaergaard, AD, Ellervik, C, Tybjaerg-Hansen, A, Axelsson, CK, Grønholdt, ML, Grande, P, Jensen, GB, Nordestgaard, BG, Tybjaerg-Hansen, A, Kjaergaard, AD, Ellervik, C, Axelsson, CK, Grønholdt, M-L, Grande, P & Nordestgaard, BG 2007, 'Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis', Circulation, vol. 115, no. 7, pp. 861-71. https://doi.org/10.1161/CIRCULATIONAHA.106.615567

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title = "Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis",

abstract = "Background- We hypothesized that the estrogen receptor (ESR1) IVS1-397T/C polymorphism affects high-density lipoprotein cholesterol response to hormone replacement therapy and risk of cardiovascular disease (CVD), cancer of reproductive organs, and hip fracture. Methods and Results- We studied cross-sectionally 9244 individuals from the Danish general population and followed them up for 23 to 25 years. End points were CVD (ischemic heart disease, myocardial infarction, angina pectoris, ischemic cerebrovascular disease, ischemic stroke, other ischemic cerebrovascular disease, venous thromboembolism, deep vein thrombosis, and pulmonary embolism), cancer of reproductive organs (breasts, ovaries, uterus, and prostate), and hip fracture. We also studied patients with ischemic heart disease (n=2495), ischemic cerebrovascular disease (n=856), and breast cancer (n=1256) versus general population controls. The CC, CT, and TT genotypes had general population frequencies of 21%, 50%, and 29%, respectively. Cross-sectionally, genotype did not influence high-density lipoprotein cholesterol response to hormone replacement therapy. In the cohort study, there were no differences in risks of CVD, cancer of reproductive organs, or hip fracture between genotypes. In case-control studies, risk of CVD did not differ between genotypes; however, the odds ratio for breast cancer in women with TT versus CC genotypes was 1.4 (95% CI, 1.1 to 1.7). Meta-analysis in men of 6 previous and the present 2 studies, including 4799 cases and 12 190 controls, showed odds ratios in CC versus CT and TT genotypes for fatal and nonfatal myocardial infarction of 0.81 (95% CI, 0.59 to 1.12) and 1.08 (95% CI, 0.97 to 1.21). Conclusions- ESR1 IVS1-397T/C polymorphism does not influence high-density lipoprotein cholesterol response to hormone replacement therapy or risk of CVD, most cancers of reproductive organs, or hip fracture",

author = "AD Kjaergaard and C Ellervik and A Tybjaerg-Hansen and CK Axelsson and ML Gr{\o}nholdt and P Grande and Jensen, {Gorm B} and BG Nordestgaard and Anne Tybjaerg-Hansen and Kjaergaard, {Alisa D} and Christina Ellervik and Axelsson, {Christen Kirk} and Marie-Louise Gr{\o}nholdt and Peer Grande and Nordestgaard, {B{\o}rge G}",

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volume = "115",

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TY - JOUR

T1 - Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture

T2 - cross-sectional, cohort, and case-control studies and a meta-analysis

AU - Kjaergaard, AD

AU - Ellervik, C

AU - Tybjaerg-Hansen, A

AU - Axelsson, CK

AU - Grønholdt, ML

AU - Grande, P

AU - Jensen, Gorm B

AU - Nordestgaard, BG

AU - Tybjaerg-Hansen, Anne

AU - Kjaergaard, Alisa D

AU - Ellervik, Christina

AU - Axelsson, Christen Kirk

AU - Grønholdt, Marie-Louise

AU - Grande, Peer

AU - Nordestgaard, Børge G

PY - 2007

Y1 - 2007

N2 - Background- We hypothesized that the estrogen receptor (ESR1) IVS1-397T/C polymorphism affects high-density lipoprotein cholesterol response to hormone replacement therapy and risk of cardiovascular disease (CVD), cancer of reproductive organs, and hip fracture. Methods and Results- We studied cross-sectionally 9244 individuals from the Danish general population and followed them up for 23 to 25 years. End points were CVD (ischemic heart disease, myocardial infarction, angina pectoris, ischemic cerebrovascular disease, ischemic stroke, other ischemic cerebrovascular disease, venous thromboembolism, deep vein thrombosis, and pulmonary embolism), cancer of reproductive organs (breasts, ovaries, uterus, and prostate), and hip fracture. We also studied patients with ischemic heart disease (n=2495), ischemic cerebrovascular disease (n=856), and breast cancer (n=1256) versus general population controls. The CC, CT, and TT genotypes had general population frequencies of 21%, 50%, and 29%, respectively. Cross-sectionally, genotype did not influence high-density lipoprotein cholesterol response to hormone replacement therapy. In the cohort study, there were no differences in risks of CVD, cancer of reproductive organs, or hip fracture between genotypes. In case-control studies, risk of CVD did not differ between genotypes; however, the odds ratio for breast cancer in women with TT versus CC genotypes was 1.4 (95% CI, 1.1 to 1.7). Meta-analysis in men of 6 previous and the present 2 studies, including 4799 cases and 12 190 controls, showed odds ratios in CC versus CT and TT genotypes for fatal and nonfatal myocardial infarction of 0.81 (95% CI, 0.59 to 1.12) and 1.08 (95% CI, 0.97 to 1.21). Conclusions- ESR1 IVS1-397T/C polymorphism does not influence high-density lipoprotein cholesterol response to hormone replacement therapy or risk of CVD, most cancers of reproductive organs, or hip fracture

AB - Background- We hypothesized that the estrogen receptor (ESR1) IVS1-397T/C polymorphism affects high-density lipoprotein cholesterol response to hormone replacement therapy and risk of cardiovascular disease (CVD), cancer of reproductive organs, and hip fracture. Methods and Results- We studied cross-sectionally 9244 individuals from the Danish general population and followed them up for 23 to 25 years. End points were CVD (ischemic heart disease, myocardial infarction, angina pectoris, ischemic cerebrovascular disease, ischemic stroke, other ischemic cerebrovascular disease, venous thromboembolism, deep vein thrombosis, and pulmonary embolism), cancer of reproductive organs (breasts, ovaries, uterus, and prostate), and hip fracture. We also studied patients with ischemic heart disease (n=2495), ischemic cerebrovascular disease (n=856), and breast cancer (n=1256) versus general population controls. The CC, CT, and TT genotypes had general population frequencies of 21%, 50%, and 29%, respectively. Cross-sectionally, genotype did not influence high-density lipoprotein cholesterol response to hormone replacement therapy. In the cohort study, there were no differences in risks of CVD, cancer of reproductive organs, or hip fracture between genotypes. In case-control studies, risk of CVD did not differ between genotypes; however, the odds ratio for breast cancer in women with TT versus CC genotypes was 1.4 (95% CI, 1.1 to 1.7). Meta-analysis in men of 6 previous and the present 2 studies, including 4799 cases and 12 190 controls, showed odds ratios in CC versus CT and TT genotypes for fatal and nonfatal myocardial infarction of 0.81 (95% CI, 0.59 to 1.12) and 1.08 (95% CI, 0.97 to 1.21). Conclusions- ESR1 IVS1-397T/C polymorphism does not influence high-density lipoprotein cholesterol response to hormone replacement therapy or risk of CVD, most cancers of reproductive organs, or hip fracture

U2 - http://dx.doi.org/10.1161/CIRCULATIONAHA.106.615567

DO - http://dx.doi.org/10.1161/CIRCULATIONAHA.106.615567

M3 - Journal article

SN - 0009-7322

VL - 115

SP - 861

EP - 871

JO - Circulation

JF - Circulation

IS - 7

ER -

Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis

Abstract

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