Feb. 28, 2007 A large Danish study rebuts the accepted idea that differences in an estrogen gene (ESR1) affect the risk of heart attack and stroke in response to hormone replacement therapy. However, the study -- published in Circulation: Journal of the American Heart Association -- found that the gene may be associated with an increased risk of breast cancer. The two forms of the ESR1 gene, called alleles, are the C allele and the T allele. A person has two copies of any gene; thus, someone can have two copies of the C allele (CC), two of the T allele (TT), or one of each (CT).
Estrogens are important hormones that take action when they come in contact with estrogen receptors on the body's cells. They influence multiple organ systems in men and women, including cardiovascular, reproductive and skeletal systems. Therefore, genetic differences in estrogen receptors could influence risk of cardiovascular disease (CVD), cancer of reproductive organs and osteoporosis-linked bone fracture in the presence of supplemental hormone therapy.
In the largest and statistically most powerful study addressing whether risk of disease is associated with ESR1 gene type, researchers followed 2,495 patients with ischemic heart disease, 856 with ischemic cerebrovascular disease (including stroke) and 1,256 with breast cancer for up to 25 years. They also gathered data on 9,244 people from the Danish general population.
The researchers compared rates of CVD (heart attack, angina, stroke, venous thromboembolism), cancer of reproductive organs (breasts, ovaries, uterus and prostate), and hip fracture among the different groups, according to their ESR1 gene type. In the general population, 21 percent of people were CC, 50 percent were CT and 29 percent were TT.
The researchers found that differences in the ESR1 receptor gene do not influence high density lipoprotein cholesterol response to hormone replacement therapy or risk of CVD, most cancers of reproductive organs or hip fracture. However, the odds for breast cancer in women with TT were 40 percent higher than in women with CC.
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