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, Alisa D
AU - Ellervik, Christina
AU - Tybjaerg-Hansen, Anne
AU - Axelsson, Christen Kirk
AU - Grønholdt, Marie-Louise
AU - Grande, Peer
AU - Jensen, Gorm B
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
KW - Alleles
KW - Breast Neoplasms
KW - Cardiovascular Diseases
KW - Case-Control Studies
KW - Cohort Studies
KW - Cross-Sectional Studies
KW - Denmark
KW - Estrogen Receptor alpha
KW - Estrogen Replacement Therapy
KW - Female
KW - Follow-Up Studies
KW - Genital Neoplasms, Female
KW - Genotype
KW - Hip Fractures
KW - Humans
KW - Lipoproteins, HDL
KW - Male
KW - Neoplasms
KW - Polymorphism, Genetic
KW - Prostatic Neoplasms
KW - Risk
U2 - 10.1161/CIRCULATIONAHA.106.615567
DO - 10.1161/CIRCULATIONAHA.106.615567
M3 - Journal article
C2 - 17309937
SN - 0009-7322
VL - 115
SP - 861
EP - 871
JO - Circulation (Baltimore)
JF - Circulation (Baltimore)
IS - 7
ER -