Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis.
BACKGROUND
We hypothesized that the estrogen receptor alpha (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.


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.
Kjaergaard
Alisa D
AD
Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Ellervik
Christina
C
Tybjaerg-Hansen
Anne
A
Axelsson
Christen Kirk
CK
Grønholdt
Marie-Louise M
ML
Grande
Peer
P
Jensen
Gorm B
GB
Nordestgaard
Børge G
BG
D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006620:Hip Fractures / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008075:Lipoproteins, HDL; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics; D012306:Risk
D047628:Estrogen Receptor alpha; D008075:Lipoproteins, HDL