STEROID HORMONES, ALPHA FETOPROTEIN AND BREAST CANCER

描述：（申请人的描述）本研究旨在评估 血清类固醇激素浓度的独立效应和联合效应 妊娠期间甲胎蛋白 (AFP) 水平对长期风险的影响 乳腺癌。 尽管足月妊娠的机制 目前尚不清楚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 水平升高被推测为 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。 这个 研究将是第一个直接评估这些因素综合效应的研究 怀孕期间人血清中天然存在的物质及其 调节乳腺癌风险的潜力。 拟议的研究将利用现有的数据源和储存的血清 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和 1959年至1966年期间的发展研究。 病例 (N=247) 是 定义为经组织学证实患有乳腺癌的女性 1969 年 1 月至 1992 年 6 月通过加州癌症登记处。 对照组（N = 463）是从队列的其余成员中选出的， 使用随机方法按年龄（大约 2 比 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，例如 年龄、种族、首次足月妊娠年龄、之前妊娠次数、 初潮年龄、体重、身高和酒精摄入量通过 孕期访谈问卷。 在之前的一项研究中 研究人员小组测量了获得的储存血清中的 AFP 水平 上次怀孕的妊娠晚期。 AFP 水平升高 发现可以降低首次接受乳腺癌治疗的女性随后患乳腺癌的风险 26 岁之前足月妊娠。本研究将建立在 这些数据通过测量雌二醇、雌三醇、雌酮和孕酮来获得 先前测定 AFP 血清水平的相同等份血清。 血清雌激素（雌二醇、雌三醇或雌酮）水平的变化和 将评估孕酮和雌激素：孕酮比率 与乳腺癌风险的关联。 类固醇之间的关联 假设激素水平和乳腺癌风险之间存在差异 血清 AFP 浓度高或低，有激素相关风险 在 AFP 值高的人中减弱。

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.