STEROID HORMONES, ALPHA FETOPROTEIN AND BREAST CANCER

描述：（申请人描述）本研究旨在评价 血清类固醇激素浓度的独立和联合作用 和甲胎蛋白（AFP）水平在怀孕期间的长期风险， 乳腺癌 虽然足月妊娠的机制， 目前还不了解对乳腺癌的长期保护， 越来越多的实验证据表明， 妊娠蛋白AFP。 AFP水平升高被假设为 通过与雌激素相互作用降低乳腺癌风险，从而调节 雌激素诱导的乳腺上皮细胞增殖。 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。 怀孕期间人体血清中天然存在的物质及其 调节乳腺癌风险的潜力。 拟定研究将利用现有数据源和库存血清， 在一组孕妇中进行病例对照研究， 参加了加州大学伯克利分校的儿童健康项目， 1959-1966年期间的发展研究。 病例（N=247） 定义为经组织学证实的乳腺癌女性， 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， 使用随机分组，按年龄（约2：1）与病例匹配的概率 招聘 有关乳腺癌主要危险因素的信息，如 年龄、种族、首次足月妊娠时的年龄、既往妊娠次数， 月经初潮年龄、体重、身高和饮酒量通过以下方法获得： 怀孕期间的问卷调查。 在之前的一项研究中， 在研究者组中，在获得的储存血清中测量AFP水平 在最后一次怀孕的第三个三个月。 AFP水平升高， 发现可以降低女性乳腺癌的后续风险， 26岁之前的足月妊娠。 本研究报告将以 这些数据是通过测量雌二醇、雌三醇、雌酮和孕酮， 先前测定AFP血清水平的相同血清等分试样。 血清雌激素（雌二醇、雌三醇或雌酮）水平的变化， 孕酮和雌激素：孕酮比率将被评估， 与乳腺癌风险的关联。 类固醇与 激素水平和乳腺癌的风险是假设不同的那些 血清AFP浓度高或低，有死亡相关风险 AFP值高的患者中，AFP值降低。

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.