DIET AND ESTROGEN RECEPTORS IN NORMAL MAMMARY TISSUE

申请人的描述 一种疾病的主要原因应该能够解释它的主要原因 流行病学模式。然而，关于乳腺癌，似乎有 成为一个重大的悖论。内源性雌激素在卵巢癌病因学中的作用 女性乳腺癌的定义很明确。然而，两者之间的差异 高加索和亚洲妇女在雌激素产生和血液方面 水平，不足以解释乳房5倍的差异 这些组之间的癌症发病率。考虑到雌激素的专有作用 雌激素反应受体在正常乳腺组织中的表达 组织可能是乳腺癌风险的主要决定因素，也是一个重要的 乳腺癌发病率显著变异的解释因素 全世界。多项研究表明，乳腺癌的风险可能是 雌激素受体高表达时升高，但外源性决定因素 雌激素受体的表达情况尚未确定。成年后的饮食 似乎不是乳腺癌风险的强大决定因素；然而， 食用蔬菜、水果和橄榄油与 风险，而酒精摄入量和动物来源的饱和脂肪可能 增加风险。因为食物种类和营养素可能会影响乳腺癌 雌激素受体-a(ER-a)在正常乳腺组织中的表达及其危险性 可能会改变这种风险，我们希望调查饮食是否会影响 ER-a在正常乳腺上皮中的表达具体来说，我们希望 调查一下：1)高水果蔬菜或高橄榄的饮食 油的摄入减少了乳腺组织中ER-a的表达，以及2-)是否 高动物脂肪、n-6多不饱和脂肪或酒精摄入量高的饮食 增加乳腺组织中ER-a的表达。在一位少校的乳房诊所 希腊雅典大学医院，约4000名女性每年接受 乳房X光检查。每年，超过300个非恶性乳腺 活组织检查是从这些妇女身上提取的。因此，在18个月的时间里，我们 估计将有440名未患乳腺癌的妇女进行活组织检查。 这些女性将就人口统计、社会经济、 生殖和生物医学变量，他们将完成一个经过验证的 广泛的食物频率调查问卷。ER-a阳性细胞百分率 (ER-oc百分比)将通过免疫组织化学和 半定量PCR法。所有统计分析都将使用线性 根据饮食和其他因素确定ER-a百分比分布的模型 协变量。

APPLICANT'S DESCRIPTION The major causes of a disease should be able to explain its dominant epidemiological patterns. Yet, with respect to breast cancer, there appears to be a major paradox. The role of endogenous estrogens in the etiology of breast cancer in women is well defined. However, differences between Caucasian and Asian women, with respect to estrogen production and blood levels, are not sufficiently large to explain the 5-fold difference in breast cancer incidence between these groups. Given the obligate role of estrogen receptors in estrogen response expression of these receptors in normal breast tissue could be a major determinant of breast cancer risk and an important explanatory factor of the marked variability in breast cancer incidence worldwide. A number of studies have indicated that breast cancer risk may be elevated when estrogen receptor expression is high, but exogenous determinants of estrogen receptor expression have not been identified. Diet in adult life does not appear to be a powerful determinant of breast cancer risk; however, consumption of vegetables, fruits, and olive oil are inversely associated with risk, whereas alcohol intake and perhaps saturated fat of animal origin may increase risk. Because food groups and nutrients may affect breast cancer risk, and expression of estrogen receptor-a (ER-a) in normal mammary tissue may modify this risk, we wish to investigate whether diet may affect the expression of ER-a in normal mammary epithelium. Specifically, we wish to investigate whether 1-) a diet high in fruits and vegetables or high in olive oil intake reduces ER-a expression in the mammary tissue, and 2-) whether a diet high in animal fat, in n-6 polyunsaturated fats, or alcohol consumption increases ER-a expression in mammary tissue. In the breast clinic of a major university hospital in Athens, Greece, some 4,000 women undergo annual mammography screening. Every year, more than 300 non-malignant breast biopsies are taken from these women. Thus, over a period of 18 months we estimate that biopsies from 440 women without breast cancer will be available. These women will be interviewed in person for demographic, socioeconomic, reproductive and biomedical variables, and they will complete a validated extensive food frequency questionnaire. The percent of ER-a positive cells (ER-oc+ percent) will be determined through immunohistochemistry and through semi-quantitative PCR. All statistical analyses will conducted using linear models to determine the distribution of ER-a percent, by diet and other covariates.