ER GENE POLYMORPHISMS AND BREAST AND ENDOMETRIAL CANCER

我们的目标是在一个种族同质的人群中， 假设个体对雌激素的敏感性存在差异- 由雌激素受体（ER）基因多态性引起的雌激素受体（ER）基因多态性 女性患乳腺癌和子宫内膜癌的风险。几种多态性 ER基因中的突变最近被描述，但没有研究表明 充分评估其恶性转化的意义。 我们的方法具有独特的成本效益，因为它建立在两个最近 完成的、协调的、全国范围的、以人群为基础的病例控制 瑞典的乳腺癌和子宫内膜癌研究（由NIH资助， 美国癌症协会），包括50-74岁的妇女 新诊断的乳腺癌（n= 3，900），子宫内膜癌 （n= 1，000）和对照组（n= 3，500）。关于生殖的详细信息 因素和外源激素的使用使得这里提出的研究 专注于从不使用者和长期使用者。我们将随机抽取 900例乳腺癌病例，900例子宫内膜癌病例，1034例 对照组（预期900，子宫）。对于类别内的分析 绝经期激素的使用，该样品将富集额外的 对照组和长期服用绝经后避孕药的癌症病例 激素，共3,394名受试者的样本。DNA基因 将在来自非恶性细胞的病例中进行分析。 组织标本，以及血液中白细胞的对照 样品遗传分析将评估Xba I和 内含子1中的Pvu II限制性位点，一个二核苷酸重复序列 多态性上游的基因，和两个多态性外显子3和 4.这些遗传变异与以下风险的总体关联 乳腺癌和子宫内膜癌将在随机样本中评估， 小心控制外源性激素的使用和乳腺癌的风险 因素绝经期激素使用分层内的其他分析 和其他风险因素将进行探讨的差异， 多态性的影响。研究人群将足够大， 以确保在大部分地区检测到2.0以下的相对风险， 分析，以及绝大多数分析中从未使用过绝经期 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.