ER GENE POLYMORPHISMS AND BREAST AND ENDOMETRIAL CANCER

我们的目标是在种族同质的人群中测试 假设雌激素敏感度的个体差异- 由雌激素受体(ER)基因的多态引起--影响 女性患乳腺癌和子宫内膜癌的风险。几种多态现象 最近已被描述在ER基因中，但还没有研究 充分评估了它们对恶变的重要性。 我们的方法具有独特的成本效益，因为它建立在最近的两个基础上 全面、协调、全国性、以人口为基础的病例控制 瑞典的乳腺癌和子宫内膜癌研究(由NIH和 分别为美国癌症协会)涵盖50-74岁的女性 新诊断的乳腺癌(n=3900)，子宫内膜癌 L组，000例；对照组，3,500例。有关生殖的详细信息 外源激素的因素和使用使这里提出的研究成为可能 着眼于从不使用和长期使用的用户。我们将随机选择 900例乳腺癌，900例子宫内膜癌，1034例 对照组(预计900人有子宫)。用于类别内的分析 更年期激素的使用，这个样本将增加额外的 长期使用更年期药物的对照和癌症病例 荷尔蒙，总共3394名受试者的样本。用于遗传的DNA 将对来自非恶性细胞的病例进行分析 组织标本，以及血液中白细胞的对照 样本。遗传分析将评估Xba I和Xba I的多态 内含子1的Pvu II酶切位点，一个二核苷酸重复序列 基因上游的多态，外显子3和外显子3的两个多态 4.这些基因变异对罹患糖尿病风险的总体关联 乳腺癌和子宫内膜癌将在随机样本中进行评估， 仔细控制外源性激素的使用和乳腺癌风险 各种因素。更年期激素使用层次内的其他分析 和其他风险因素将被进行，以探索差异在 多态的影响。研究人群将足够大 确保在大多数总体情况下检测到2.0以下的相对风险 分析，以及对从未使用更年期的人进行的大多数分析 荷尔蒙。

Our objective is to test, in an ethnically homogenous population, the hypothesis that individual variation in the sensitivity to estrogens- caused by polymorphism in the estrogen receptor (ER) gene-affects a woman's risk of breast and endometrial cancer. Several polymorphisms in the ER gene have recently been described, but no study has adequately assessed their significance for malignant transformation. Our approach is uniquely cost-effective since it builds on two recently completed, coordinated, nationwide, population-based case-control studies of breast and endometrial cancer in Sweden (funded by NIH and American Cancer Society, respectively) encompassing women aged 50-74 with newly diagnosed breast cancer (n=3,900), endometrial cancer (n=l,000), and controls (n=3,500). Detailed information on reproductive factors and use of exogenous hormones allows the study proposed here to focus on never-users and long-term users. We will randomly select 900 breast cancer cases, 900 endometrial cancer cases, and 1,034 Controls (expecting 900 with a uterus). For analyses within categories of menopausal hormone use, this sample will be enriched with additional controls and cancer cases who were long-term users of menopausal hormones, for a total sample of 3,394 subjects. DNA for genetic analysis will be obtained in the cases from non-malignant cells in the tissue specimens, and among the controls from leucocytes in blood samples. The genetic analyses will assess polymorphisms in Xba I and Pvu II restriction sites in intron 1, a dinucleotide repeat polymorphism upstream Of the gene, and two polymorphisms in exons 3 and 4. The overall associations of these genetic variants on the risk of breast and endometrial cancer will be assessed in the random sample, with careful control for exogenous hormone use and breast cancer risk factors. Additional analyses within strata of menopausal hormone use and other risk factors will be conducted to explore differences in the effect of the polymorphisms. The study population will be large enough to ensure detection of relative risks under 2.0 in most of the overall analyses, and for most analyses among never-users of menopausal hormones.