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.

我们遵循来自美国各地的各种志愿妇女和35至74岁之间的波多黎各妇女，她们患有乳腺癌姐妹，但在加入研究时没有乳腺癌本身。入学时，使用计算机辅助电话访谈和邮寄问卷收集了有关潜在风险因素和当前健康状况的数据。在家庭探访中收集了血液，尿液和环境样本，并在筑巢的研究中用于患有乳腺癌（或其他疾病）的嵌套研究，以及那些没有患者的样本。每年都会跟踪该队列的重要状态和重大健康成果。每2 - 3年就会完成有关健康结果，环境和生活方式暴露以及特殊主题的详细后续调查表。为患有癌症或其他感兴趣疾病的患者检索病历和肿瘤组织（针对乳腺癌病例）。该队列在2003年至2009年之间被招收。将近51,000名妇女完成了所有基线研究活动。年度更新的响应率在90-98％之间。 第一次姐妹研究双年展的随访调查于2012年6月完成；从48,090名妇女获得了95％的反应。随着下一轮详细的后续行动，该后续行动始于2012年1月，该研究已转移到三年期管理，以减轻参与者的负担并简化工作流程。迄今为止，已经从20,000多名合格妇女那里收集了三年期问卷。超过1,800名妇女报告诊断为乳腺癌或DCIS/LCIS；诊断后的6个月，正在寻求病历和肿瘤组织。 还寻求报告其他癌症类型的女性，迄今为止有1,600多名妇女。 2012年4月，姊妹研究科学咨询委员会召集了优先级长期研究策略，以解决与环境和基因在乳腺癌中的作用有关的问题。在董事会的建议中，姊妹研究正在组建一个工作组，以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持续时间，就业和工作时间表以及端粒长度，黑人和白人妇女的生活方式行为，自我报告的体重和身高的准确性和可靠性，黑人女性的子宫平滑肌瘤的早期生活因素以及早期的生活因素以及富含类风湿关节炎的风险。使用涉及前350例乳腺癌病例的病例研究中的数据和从同类中选出的700名妇女的样本，我们完成了外周血和乳腺癌风险的端粒长度的分析，在我们的前瞻性收集数据中没有发现关联。在609例（301例和301例案例和308个亚幼体成员）绝经后妇女的尿尿前列腺素E2-替代物（PGE-M）和乳腺癌风险中，几种已知的促和抗炎因素与尿中PGE-M和绝经后乳腺癌的妇女在不适用的妇女中增加了尿中的PGE-M，而尿液中的妇女不断增加，而这些妇女的使用量增加了，而这些妇女的使用水平增加了，这些妇女的使用水平增加了。 （NSAIDS）。这些结果支持前列腺素E2和炎症在乳腺癌发生中的作用，这可以通过生活方式和药理干预措施来修改。 正在进行对1,800名参与者及其母亲的验证研究进行的分析，旨在评估妇女在基线上收集到的早期生活的信息，包括有关母亲怀孕的信息。比较母亲和女儿反应的初步结果表明，对所研究的大多数因素来说，中等或更好的一致性。正在进行的其他研究包括早期生命因素和外周血的端粒长度以及与初潮的年龄有关，并分析研究了与乳腺癌风险有关的几个因素，包括遗传变异，职业有机溶剂暴露，肥胖，肥胖和抗生素使用。一系列分析正在研究与诸如子宫内的二乙基苯甲醇和体育活动等暴露有关的DNA全球和基因特异性甲基化，以及与乳腺癌风险有关。在国家科学会议上提出了一些分析的结果，并准备出版手稿。 姐妹研究在华盛顿大学的共同投资者中完成了地理编码参与者的地址，从而可以在参与者住所附近获得环境暴露数据，例如当前和历史空气污染测量。对住宅空气污染和血压暴露的研究正在进行中。未来的计划包括开发一个综合统计框架，用于评估暴露于污染物多层混合物的健康影响，以及对空气和其他污染物的研究以及哮喘和乳腺癌的风险。 这项姐妹研究是在疾病控制与预防中心（CDC）的癌症预防和控制司的一组中进行乳腺癌幸存者的研究，该研究由流行病学和应用研究部门负责人玛丽·怀特（Mary White）博士领导。这项工作部分是由年轻妇女的乳房健康意识和对被诊断为乳腺癌法案的年轻妇女的支持，这是2010年的国会法案，也称为《早期法案》。 2011年1月，关于最先进的乳腺癌生存研究的专家研讨会举行，提出了关于姊妹研究如何最好地为这一研究领域做出贡献的建议。这项合作涉及两项特殊调查的开发和管理。首先于2012年4月完成，涵盖了乳腺癌筛查实践，有关癌症的家庭交流以及与乳腺癌参与者及其家人的姐妹的影响；从20,000名妇女中收集了反应，并且正在进行数据分析。目前正在开发的第二项调查是针对被诊断出患有乳腺癌的女性，其中包括年轻女性特别感兴趣的主题，例如身体形象，工作与生活的平衡，人际关系，亲密关系和生育能力。这些调查将共同提高我们对癌症在乳腺癌幸存者及其家人生活中的影响的理解，并提供有关幸存者生活质量，身体和情感健康，生活方式和环境变化以及癌症治疗和随访护理的信息，这将有助于确定与诊断后健康生活有关的因素。 姐妹研究参加了国家癌症研究所队列联盟，该团体促进了从各个队列研究中汇集数据的汇集，以创建足够大的数据库，以研究稀有癌症的危险因素。姊妹研究为在头颈，胆囊和卵巢癌上进行的队列联盟研究做出了贡献，从而使其能够自行解决研究。姊妹研究还是国际协调计划（蒙特利尔麦吉尔大学）的成员，该计划的旨在协调在不同研究中收集的数据，以便使用大型高质量数据库的协作研究。 一项称为两项姐妹研究的相关研究于2010年12月完成了入学率。这项基于家庭的关于年轻发作乳腺癌的环境和遗传危险因素的研究是在姐妹研究的基础上建立在姐妹研究的基础上，通过招募参与者患有乳腺癌的姐妹和父母，他们被要求为DNA来源提供唾液样本，请参阅Weinberg Z01-ES01-ES044005。