DIET AND ESTROGEN RECEPTORS IN NORMAL MAMMARY TISSUE

申请人描述 一种疾病的主要原因应该能够解释其主要原因。 流行病学模式。 然而，关于乳腺癌， 成为一个主要的悖论。 内源性雌激素在子宫内膜异位症发病中的作用 女性乳腺癌的定义很明确。 然而， 高加索和亚洲女性，就雌激素产生和血液 水平，并不足以解释乳腺癌的5倍差异， 这些人群之间的癌症发病率。 考虑到雌激素的强制作用 雌激素反应中的受体这些受体在正常乳腺中的表达 组织可能是乳腺癌风险的主要决定因素， 乳腺癌发病率显著变化的解释因素 国际吧 许多研究表明，乳腺癌的风险可能是 当雌激素受体表达高时升高，但外源性决定因素 雌激素受体的表达尚未确定。 成人饮食 似乎不是乳腺癌风险的有力决定因素;然而， 蔬菜、水果和橄榄油的摄入量与 风险，而酒精摄入和动物源性饱和脂肪可能 增加风险。 因为食物组和营养素可能会影响乳腺癌 正常乳腺组织中雌激素受体-a（ER-a）的表达 可能会改变这种风险，我们希望调查饮食是否会影响 ER-α在正常乳腺上皮中的表达。 具体而言，我们希望 调查是否1-）高水果和蔬菜或高橄榄的饮食 油摄入减少乳腺组织中ER-α的表达，以及2-） 高动物脂肪饮食，n-6多不饱和脂肪，或饮酒 增加乳腺组织中ER-α的表达。 在一个少校的乳房诊所里 在希腊雅典的一所大学医院，大约4,000名妇女每年接受 乳房X光检查 每年有300多例非恶性乳腺癌 对这些妇女进行活组织检查。 因此，在18个月的时间里， 估计将有440名没有乳腺癌的妇女的活检。 这些妇女将亲自接受采访，了解人口统计学、社会经济学、 生殖和生物医学变量，他们将完成一个验证 广泛的食物频率问卷。 ER-α阳性细胞百分比 （ER-α +百分比）将通过免疫组织化学和 半定量PCR。 所有统计分析将使用线性 模型来确定ER-α百分比的分布，通过饮食和其他 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.