Environmental and Genetic Risk Factors For Breast Cancer: The Sister Study

乳腺癌的环境和遗传风险因素：姐妹研究

• 批准号: 8553694
• 负责人: Dale P Sandler
• 金额: $ 119.83万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8553694
• 关键词: Accounting; Address; Adult; Affect; African American; Age; Age at Menarche; Agreement; Air; Air Pollution; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Applied Research; Area; Asthma; Awareness; Behavior; Blood; Blood Pressure; Body Image; Breast; Breast Cancer Detection; Breast Cancer Risk Factor; Breast Cancer Treatment; Cancer Control; Cancer Etiology; Cancer Survivor; Cancer Survivorship; Caring; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemicals; Cohort Studies; Collaborations; Communication; Complex; Computer Assisted; DNA; Data; Data Analyses; Databases; Daughter; Development; Diagnosis; Diethylstilbestrol; Dinoprostone; Disease; Division of Cancer Prevention; Eating; Educational workshop; Emotional; Employment; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Equilibrium; Ethnic Origin; Etiology; Exposure to; Family; Family Practice; Fertility; Frequencies; Funding; Future; Genes; Genetic; Goals; Head; Head and Neck Cancer; Health; Health Status; Height; Hematopoietic Neoplasms; Home visitation; House Call; In Situ; Individual; Inflammation; Inflammatory; International; Intervention; Joints; Length; Life; Life Style; Mails; Malignant Neoplasms; Malignant neoplasm of gallbladder; Malignant neoplasm of ovary; Manuscripts; Measurement; Medical; Medical Records; Meta-Analysis; Methylation; Mothers; National Cancer Institute; Noninfiltrating Intraductal Carcinoma; Obesity; Occupational; Oncogenes; Onset of illness; Organic solvent product; Outcome; Paper; Parents; Participant; Patient Self-Report; Pattern; Pharmaceutical Preparations; Physical activity; Postmenopause; Pregnancy; Preparation; Prospective Studies; Publications; Puerto Rico; Quality of life; Questionnaires; Race; Recommendation; Recruitment Activity; Reporting; Research; Research Personnel; Retrospective Studies; Rheumatoid Arthritis; Risk; Risk Factors; Role; Saliva; Sampling; Schedule; Series; Sister; Sleep; Source; Suggestion; Surveys; Survivors; Techniques; Telephone Interviews; Testing; Time; Tumor Tissue; Universities; Update; Urine; Uterine Fibroids; Vital Status; Washington; Weight; Woman; Women' s Health; Work; base; breast cancer diagnosis; cancer risk; cancer therapy; cancer type; carcinogenesis; cohort; design; disorder prevention; follow-up; gene environment interaction; genetic risk factor; genetic variant; in utero; interest; intimate behavior; lobular breast carcinoma in situ; malignant breast neoplasm; meetings; member; mortality; peripheral blood; pollutant; prospective; research study; residence; response; telomere; urinary; validation studies; volunteer; working group; young woman

We are following a diverse cohort of volunteer women from throughout the US and Puerto Rico between the ages of 35 and 74 who have a sister with breast cancer but did not have breast cancer themselves when they joined the study. At enrollment, data on potential risk factors and current health status were collected using computer assisted telephone interviews and mailed questionnaires. Blood, urine, and environmental samples were collected in a home visit and banked for future use in nested studies of women who develop breast cancer (or other diseases) and a sample of those who don't. The cohort is tracked annually for changes in vital status and major health outcomes. Detailed follow-up questionnaires on health outcomes, environmental and lifestyle exposures, and special topics are completed every 2-3 years. Medical records and tumor tissue (for breast cancer cases) are retrieved for those who develop cancer or other conditions of interest. The cohort was enrolled between 2003 and 2009. Nearly 51,000 women completed all baseline study activities. The response rates for annual updates range from 90-98%. The first Sister Study Biennial follow-up survey was completed in June 2012; responses were obtained from 48,090 women for a response rate of 95%. With the next round of detailed follow-up, which began in January 2012, the study has shifted to triennial administration to reduce participant burden and simplify workflow. Triennial questionnaires have been collected from over 20,000 eligible women to date. More than 1,800 women have reported a diagnosis of breast cancer or DCIS/LCIS; medical records and tumor tissue are being sought for those 6 months post diagnosis. Medical records are also sought for women reporting other cancer types, over 1,600 women to date. In April 2012 the Sister Study Scientific Advisory Board convened to help prioritize a long-term research strategy for addressing questions related to the role of environment and genes in breast cancer. At the Boards suggestion, the Sister Study is assembling a working group to evaluate chemicals of current interest and suitable measurement techniques. Research studies using baseline and follow-up data are exploring risk factors for breast cancer and other health conditions. Recent papers have examined eating patterns and sleep duration, employment and work schedule and telomere length, lifestyle behaviors in black and white women, accuracy and reliability of self-reported weight and height, early life factors in relation to uterine leiomyomata in black women, and early life factors and the risk of rheumatoid arthritis in adulthood. Using data from a case-cohort study involving the first 350 breast cancer cases and a sample of 700 women selected from the cohort, we completed an analysis of telomere length in peripheral blood and breast cancer risk, finding no association in our prospectively collected data. In a study of urinary prostaglandin E2-metabolite (PGE-M) and breast cancer risk in 609 (301 cases and 308 subcohort members) postmenopausal women, several known pro- and anti-inflammatory factors were associated with urinary PGE-M, and post-menopausal breast cancer risk was increased with increasing levels of urinary PGE-M among women who did not regularly use non-steroidal anti-inflammatory drugs (NSAIDs). These results support a role for prostaglandin E2 and inflammation in breast carcinogenesis, which may be modifiable by lifestyle and pharmacological interventions. Analyses are underway for a validation study of over 1,800 participants and their mothers aimed at evaluating how accurately women reported the information on early life collected at baseline, including information on their mothers pregnancy. Preliminary results comparing mothers and daughters responses suggest moderate or better agreement for most of the factors studied. Other studies in progress include early life factors and telomere length in peripheral blood as well as in relation to age at menarche, and analyses examining several factors in relation to breast cancer risk including genetic variants, occupational organic solvent exposure, adiposity, and antibiotic use. A series of analyses are examining DNA global and gene-specific methylation in relation to exposures such as diethylstilbestrol in utero and physical activity throughout the lifetime, as well as in relation to breast cancer risk. Results of several analyses have been presented at national scientific meetings and manuscripts are in preparation for publication. With co-investigators at the University of Washington, the Sister Study completed geocoding participant addresses, allowing attainment of environmental exposure data near participant residences such as current and historical air pollution measurements. A study of exposure to residential air pollution and blood pressure is in progress. Future plans include the development of a comprehensive statistical framework for assessing the health effects of exposure to multi-pollutant mixtures of pollutants, as well as the study of air and other pollutants and the risk of asthma and breast cancer. The Sister Study is conducting breast cancer survivor research with a group from the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention (CDC), headed by Dr. Mary White, Chief, Epidemiology and Applied Research Branch. This effort is funded in part by the Young Women's Breast Health Awareness and Support of Young Women Diagnosed with Breast Cancer bill, a 2010 congressional bill also known as the EARLY Act. A workshop of experts was held in January 2011 on state-of-the-art breast cancer survivorship research, resulting in recommendations on how the Sister Study can best contribute to this area of research. This collaboration has involved the development and administration of two special surveys. The first, completed in April 2012, covered breast cancer screening practices, family communication about cancer, and the effect of having a sister with breast cancer participants and their families; responses were collected from 20,000 women and data analysis is in progress. The second survey, currently in development, is for women diagnosed with breast cancer and includes topics that are of particular interest to younger women such as body image, work-life balance, relationships and intimacy, and fertility. Together, these surveys will increase our understanding of the impact of cancer in the lives of breast cancer survivors and their families and provide information on survivors quality of life, physical and emotional health, changes in lifestyle and environment, and coordination of cancer treatment and follow-up care that will help identify factors related to healthy living after diagnosis. The Sister Study participates in the National Cancer Institutes Cohort Consortium, a group that facilitates the pooling of data from individual cohort studies to create databases large enough to investigate risk factors for rare cancers. The Sister Study is contributing to Cohort Consortium studies on head and neck, gallbladder and ovarian cancers, allowing it to contribute to research it could not address on its own. The Sister Study is also a member of the International Harmonization Initiative (McGill University, Montreal), an international effort that aims to harmonize data collected across different studies in order to enable collaborative research using large, high-quality databases. A related study known as the Two Sister Study completed enrollment in December 2010. This family-based study on environmental and genetic risk factors for young onset breast cancer builds on the Sister Study by recruiting the participant's sister with breast cancer and parents who were asked to provide a saliva sample for a source of DNA, see Weinberg Z01-ES044005.

我们正在追踪来自美国和波多黎各各地、年龄在 35 岁至 74 岁之间的多元化女性志愿者群体，她们的姐姐患有乳腺癌，但在参加这项研究时她们自己并未患有乳腺癌。入组时，通过计算机辅助电话访谈和邮寄问卷收集有关潜在风险因素和当前健康状况的数据。在家访时收集了血液、尿液和环境样本，并储存起来，以供将来用于对患有乳腺癌（或其他疾病）的女性和未患乳腺癌（或其他疾病）的女性进行嵌套研究。每年都会跟踪该队列的生命状态和主要健康结果的变化。每 2-3 年完成一次关于健康结果、环境和生活方式暴露以及专题的详细后续调查问卷。为那些患有癌症或其他感兴趣病症的人检索医疗记录和肿瘤组织（针对乳腺癌病例）。该队列于 2003 年至 2009 年期间入组。近 51,000 名女性完成了所有基线研究活动。年度更新的回复率在 90-98% 之间。 第一次姐妹研究双年度跟踪调查于 2012 年 6 月完成； 48,090 名女性进行了回复，回复率为 95%。随着 2012 年 1 月开始的下一轮详细随访，该研究已转向每三年一次的管理，以减轻参与者的负担并简化工作流程。迄今为止，已从超过 20,000 名符合条件的女性中收集了三年一次的调查问卷。超过 1,800 名女性报告被诊断患有乳腺癌或 DCIS/LCIS；正在寻找诊断后 6 个月的医疗记录和肿瘤组织。 还寻求报告其他癌症类型的女性的医疗记录，迄今为止已有 1,600 多名女性。 2012 年 4 月，姐妹研究科学顾问委员会召开会议，帮助确定长期研究策略的优先顺序，以解决与环境和基因在乳腺癌中的作用相关的问题。根据董事会的建议，姊妹研究正在组建一个工作组来评估当前感兴趣的化学品和合适的测量技术。 使用基线和随访数据的研究正在探索乳腺癌和其他健康状况的危险因素。最近的论文研究了饮食模式和睡眠时间、就业和工作时间表以及端粒长度、黑人和白人女性的生活方式行为、自我报告体重和身高的准确性和可靠性、与黑人女性子宫肌瘤相关的早期生活因素，以及早期生活因素和成年后患类风湿性关节炎的风险。利用涉及前 350 例乳腺癌病例和从该队列中选取的 700 名女性样本的病例队列研究数据，我们完成了外周血端粒长度与乳腺癌风险的分析，发现我们前瞻性收集的数据没有关联。在一项针对 609 名绝经后妇女（301 例和 308 名亚组成员）的尿前列腺素 E2 代谢物 (PGE-M) 和乳腺癌风险的研究中，几种已知的促炎因子和抗炎因子与尿 PGE-M 相关，并且- 不经常使用非甾体类抗炎药 (NSAID) 的女性，随着尿 PGE-M 水平的增加，绝经期乳腺癌的风险也会增加。这些结果支持前列腺素 E2 和炎症在乳腺癌发生中的作用，这种作用可以通过生活方式和药物干预来改变。 目前正在对超过 1,800 名参与者及其母亲进行的验证研究进行分析，旨在评估女性报告基线时收集的早期生活信息（包括母亲怀孕信息）的准确性。比较母亲和女儿反应的初步结果表明，大多数研究因素具有中等或更好的一致性。其他正在进行的研究包括早期生命因素和外周血中的端粒长度以及与初潮年龄的关系，并分析检查与乳腺癌风险相关的几个因素，包括遗传变异、职业有机溶剂暴露、肥胖和抗生素使用。一系列分析正在检查 DNA 整体和基因特异性甲基化与子宫内己烯雌酚等暴露和一生体力活动的关系，以及与乳腺癌风险的关系。多项分析的结果已在国家科学会议上公布，手稿正在准备出版。 姐妹研究与华盛顿大学的共同研究人员一起完成了参与者地址的地理编码，从而获得了参与者住所附近的环境暴露数据，例如当前和历史的空气污染测量值。一项关于居住区空气污染暴露与血压之间关系的研究正在进行中。未来的计划包括制定一个全面的统计框架，用于评估接触多种污染物混合物对健康的影响，以及研究空气和其他污染物以及哮喘和乳腺癌的风险。 该姐妹研究项目正在与美国疾病控制与预防中心 (CDC) 癌症预防与控制部门的一个小组一起进行乳腺癌幸存者研究，该小组由流行病学和应用研究处处长 Mary White 博士领导。这项工作的部分资金来自年轻女性乳房健康意识和对诊断患有乳腺癌的年轻女性的支持法案，该法案是 2010 年国会法案，也称为 EARLY 法案。 2011 年 1 月举行了一次关于最先进的乳腺癌生存研究的专家研讨会，会议就姐妹研究如何最好地为这一研究领域做出贡献提出了建议。此次合作涉及两项特别调查的开发和管理。第一个于 2012 年 4 月完成，涵盖乳腺癌筛查实践、关于癌症的家庭沟通，以及拥有乳腺癌参与者及其家人的姐妹的影响；已收集了 20,000 名妇女的答复，数据分析正在进行中。目前正在开展的第二项调查针对的是被诊断患有乳腺癌的女性，包括年轻女性特别感兴趣的主题，例如身体形象、工作与生活平衡、人际关系和亲密关系以及生育能力。总之，这些调查将加深我们对癌症对乳腺癌幸存者及其家人生活影响的了解，并提供有关幸存者的生活质量、身体和情感健康、生活方式和环境的变化以及癌症治疗和后续治疗协调的信息。后续护理将有助于确定诊断后与健康生活相关的因素。 姐妹研究参加了国家癌症研究所队列联盟，该组织致力于汇集各个队列研究的数据，以创建足够大的数据库来调查罕见癌症的危险因素。姐妹研究正在为队列联盟关于头颈癌、胆囊癌和卵巢癌的研究做出贡献，使其能够为它自己无法解决的研究做出贡献。姐妹研究也是国际协调倡议（蒙特利尔麦吉尔大学）的成员，该倡议是一项国际努力，旨在协调不同研究中收集的数据，以便能够使用大型、高质量数据库进行协作研究。 一项名为“两姐妹研究”的相关研究于 2010 年 12 月完成了入组。这项针对年轻发病乳腺癌的环境和遗传风险因素的家庭研究以“姐妹研究”为基础，招募了患有乳腺癌的参与者以及被要求的父母。提供 DNA 来源的唾液样本，请参阅 Weinberg Z01-ES044005。