Diet, Hormone Replacement Therapy and Breast Cancer

描述（由申请人提供）：这是I K07 CA096619-01“饮食，激素替代疗法和乳腺癌”的再申报。候选人：张淑敏，1986年获哈尔滨医科大学医学博士学位，1998年获哈佛大学公共卫生学院流行病学与营养学博士学位。2000年完成博士后培训，现为哈佛医学院（HMS）医学助理教授。她申请这个职业发展奖是为了获得成为癌症和营养流行病学独立科学家所需的方法和理论研究技能。发起人和环境：JoAnn Manson，医学博士，公共卫生博士，布里格姆妇女医院预防医学部主任，HMS医学教授，妇女健康研究ONHS的联合首席研究员。Julie Buring，理学博士，是HMS门诊护理和预防科的副主任、教授和WHS的首席研究员。他们在饮食、生活方式和慢性病领域培训了许多调查人员，并在这些领域发表了大量文章。研究：我们计划在WHS中进行一项前瞻性分析，这是一项正在进行的临床试验，在39,876名妇女中进行维生素E和低剂量阿司匹林对癌症和心血管疾病的一级预防。我们将测试4种饮食假设，即适度饮酒会增加患乳腺癌的风险，而大量摄入叶酸和纤维会降低患乳腺癌的风险；咖啡因摄入与风险无关。我们将在WHS的亚样本中将纤维摄入量与血浆内源性性类固醇激素联系起来。我们还将测试4种激素替代疗法（HRT）的假设，即长期使用雌激素加黄体酮比单独使用雌激素更能增加乳腺癌的风险；雌激素加循环黄体酮比雌激素加连续黄体酮增加风险更大；低剂量雌激素的风险低于高剂量雌激素；而在饮酒的女性中，使用雌激素与患病风险的关系更为密切。正在进行的WHS将提供更新和重复的HRT测量，基线时的综合饮食评估，以及乳腺癌的重要协变量，以及对乳腺癌病例的随访和文献（预计N = 1550）。这个项目的发现可以直接应用于降低乳腺癌风险的努力。

DESCRIPTION (provided by applicant): This is a resubmission of I K07 CA096619-01 "Diet, Hormone Replacement Therapy and Breast Cancer". Candidate: Shumin Zhang received her MD at the Harbin Medical University in 1986 and her ScD in epidemiology and nutrition at the Harvard School of Public Health in 1998. She then completed her post-doctoral training in 2000, and now is an Assistant Professor of Medicine at the Harvard Medical School (HMS). She applies for this Career Development Award to acquire the methodological and theoretical research skills needed to become an independent scientist in cancer and nutritional epidemiology. Sponsor and Environment: JoAnn Manson, MD, DrPH, is the Chief of the Division of Preventive Medicine at the Brigham and Women's Hospital, Professor of Medicine at the HMS and Co Principal investigator (Co-Principal Investigator) of the Women's Health Study ONHS). Julie Buring, ScD, is the Deputy Director of the Division, Professor of Ambulatory Care and Prevention at the HMS and Principal Investigator of the WHS. They have trained numerous investigators in the fields of diet, lifestyle and chronic diseases, areas in which they have published extensively. Research: We plan to conduct a prospective analysis within the WHS, an ongoing clinical trial of vitamin E and low-dose aspirin in the primary prevention of cancer and cardiovascular disease among 39,876 women. We will test 4 dietary hypotheses that moderate alcohol intake increases risk of breast cancer, whereas high intake of folate and fiber reduces risk; and caffeine intake is not associated with risk. We will link fiber intake to plasma endogenous sex steroid hormones in a subsample of the WHS. We will also test 4 hormone replacement therapy (HRT) hypotheses that tong-term use of estrogen plus progestin increases risk of breast cancer more than estrogen alone; estrogen plus cyclic progestin increases risk more than estrogen plus continuous progestin; low-dose estrogens confer lower risk than high-dose; and use of estrogen is more strongly associated with risk among women drinking alcohol. The ongoing WHS will provide updated and repeated measures of HRT, comprehensive dietary assessment at baseline, and important covariates for breast cancer in addition to follow-up of the cohort and documentation of breast cancer cases (expected N = 1550). The findings from this project could have direct clinical application for efforts to reduce risk of breast cancer.