STEROID HORMONES, ALPHA FETOPROTEIN AND BREAST CANCER

描述：(申请者描述)本研究旨在评估 血清类固醇激素浓度的独立作用和联合作用 和甲胎蛋白(AFP)水平对妊娠高血压病长期风险的影响 乳腺癌。尽管足月怀孕的机制使 对乳腺癌的长期保护目前还不清楚， 越来越多的实验证据表明， 妊娠蛋白甲胎蛋白。甲胎蛋白水平升高被认为是 通过与雌激素相互作用降低患乳腺癌的风险，从而调节 雌激素诱导乳房上皮细胞的增殖。这 这项研究将是第一个直接评估这些因素的综合影响的研究 妊娠期人体血清中的天然物质及其影响因素 调节乳腺癌风险的可能性。 拟议的研究将利用现有的数据源和储存的血清来 进行病例对照研究，嵌套在一群怀孕妇女中 参加了加州大学伯克利分校的儿童健康和 1959-1966年期间的发展研究。例(N=247) 定义为经组织学确诊为乳腺癌的女性 从1969年1月到1992年6月通过加州癌症登记处。 对照组(N=463)选自队列的其余成员， 使用随机化方法按年龄匹配病例的概率(约为2比1) 招聘。有关乳癌的主要危险因素的资料，例如 年龄，种族，第一次足月怀孕的年龄，以前怀孕的次数， 月经初潮年龄、体重、身高和饮酒量通过以下方式获得 孕期访谈问卷。在之前的一项由 调查组，测量获得的储存血清中的AFP水平 在最后一次怀孕的第三个三个月期间。甲胎蛋白水平升高是 发现可降低首次患乳腺癌的女性随后患乳腺癌的风险 26岁前足月怀孕。本研究的基础将是 这些数据是通过测量雌二醇、雌三醇、雌酮和孕酮从 相同等量的血清先前测定了血清AFP水平。 血清雌激素(雌二醇、雌三醇或雌酮)水平的变化和 黄体酮和雌激素与黄体酮的比率将被评估 与乳腺癌风险的关系。类固醇与癌症的关系 荷尔蒙水平和乳腺癌风险假设在这些人之间是不同的。 血清甲胎蛋白浓度高低，有激素相关风险 在AFP值高的人群中减弱。

DESCRIPTION: (Applicant's Description) This study is designed to evaluate the independent and joint effects of serum steroid hormone concentrations and alpha fetoprotein (AFP) levels during pregnancy on the long term risk of breast cancer. Although the mechanism by which full-term pregnancy confers long term protection against breast cancer is not presently understood, experimental evidence is accumulating to implicate a protective role for the pregnancy protein AFP. Elevated levels of AFP have been hypothesized to reduce breast cancer risk by interacting with estrogen, thereby regulating the estrogen-induced proliferation of epithelial cells in the breast. This study would be the first to assess directly the combined effect of these naturally occurring substances in human serum during pregnancy and their potential for modulating breast cancer risk. The proposed study will utilize an existing data source and banked serum to conduct a case-control study nested within a cohort of pregnant women who participated in the University of California at Berkeley's Child Health and Development Studies during the period of 1959-1966. Cases (N=247) were defined as women with histologically confirmed breast carcinoma identified through the California Cancer Registry from January 1969 through June 1992. Controls (N=463) were selected from the remaining members of the cohort and probability matched to cases by age (approximately 2 to 1) using randomized recruitment. Information on major risk factors for breast cancer such as age, race, age at first full-term pregnancy, number of previous pregnancies, age at menarche, body weight, height and alcohol intake were obtained by interview questionnaire during pregnancy. In a previous study by the investigator's group, AFP levels were measured in stored sera obtained during the third trimester of the last pregnancy. Elevated AFP levels were found to reduce subsequent risk of breast cancer among women with a first full-term pregnancy before the age of 26. The present study will build on these data by measuring estradiol, estriol, estrone and progesterone from the same aliquot of serum previously assayed for serum levels of AFP. Alterations in serum levels of estrogen (estradiol, estriol, or estrone) and progesterone and estrogen:progesterone ratios will be evaluated for associations with breast cancer risk. The association between steroid hormone levels and breast cancer risk is hypothesized to differ among those with high and low serum concentrations of AFP, with hormone-associated risk attenuated among those with high AFP values.