Hormone-Related Cancers

激素相关癌症

• 批准号: 7330726
• 负责人: LOUISE BRINTON
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 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/7330726
• 关键词: Hormone; Related; Cancers

This project covers a broad base of studies aimed at assessing the epidemiology of the majority of hormonally-related cancers. Major efforts are underway for breast, endometrial, ovarian, and testicular cancers. We also have an active research program on prostate cancer, covered in a separate report (Z01 CP010180-02). Our efforts for all of these cancers relate to a variety of environmental, genetic and hormonal predictors of risk.A large multi-disciplinary study has been completed in Poland to assess risk factors for breast, ovarian and endometrial cancers. The study involved collection of multiple biologic samples, with a primary aim of assessing the interactive effects of genetic and environmental determinants of risk. In addition, special components of the study addressed effects of physical activity, occupational factors, and household chemical exposures. For physical activity, special efforts were expended to improve exposure assessment, with women being asked to wear accelerometers to obtain more objective measures than interview data alone. The study also involved collection of tissue samples to enable precise tumor classification as well as assays of tumor biomarkers (including utilizing newly developed tissue microarray techniques). The large amount of data collected in this investigation are enabling a number of analyses. With respect to breast cancer, analyses are currently underway to assess effects of occupational exposures, physical activity levels, anthropometric factors, perinatal exposures, and etiologic heterogeneity by tumor stage and hormone receptor status.Another large case-control study, focused on breast cancer, has involved collection of buccal cell specimens. This effort required extensive methodologic work to determine the optimal means of collecting, processing and storing samples in order to maximize DNA yield. Breast cancer risk is also of major interest in a follow-up of a cohort of women previously screened for bone density. This resource, which previously involved collection of serologic samples and currently is collecting buccal swabs, will enable an assessment of the interrelationship of bone density, genetic factors and endogenous hormones in predicting subsequent cancer occurrence.A collaboration has recently been established with the Gynecologic Oncology Group to determine means of collecting epidemiologic data within the context of a number of ongoing trials. A standardized questionnaire has been developed and has been integrated into a large trial of endometrial. This effort should be useful in assessing epidemiologic predictors and molecular markers associated with carefully defined histologic subgroups of tumors. It is hoped that this questionnaire can be integrated into trials of other cancer sites and that additional more targeted questionnaires can be developed to address specific hypotheses of interest to gynecologic oncologists. We have learned much about the natural history of cervical cancer (as described in another project report) and are now anxious to expand our knowledge in this area to address the natural history of another gynecologic tumor, namely endometrial cancer. Endometrial hyperplasias are recognized to increase the subsequent risk of endometrial cancer, but data with which to accurately predict risk are lacking, and it is unknown how other factors might influence those risks. We are conducting a nested case-control study within a prepaid health plan to better understand the risk of endometrial cancer in women diagnosed with endometrial hyperplasia. Results from this study have the potential to improve clinical management of at-risk women and to enlighten the understanding of hormonal carcinogenesis in the endometrium. We are also in the pilot phases of developing a study to assess early markers which may be important to the development of ovarian and endometrial cancers.

该项目涵盖了广泛的研究基础，旨在评估大多数与生殖有关的癌症的流行病学。针对乳腺癌、子宫内膜癌、卵巢癌和睾丸癌的主要工作正在进行中。我们还有一项积极的前列腺癌研究计划，在单独的报告（Z 01 CP 010180 -02）中进行了介绍。我们对所有这些癌症的努力都与各种环境、遗传和激素的风险预测因素有关。波兰已经完成了一项大型多学科研究，以评估乳腺癌、卵巢癌和子宫内膜癌的风险因素。该研究涉及收集多个生物样本，主要目的是评估遗传和环境风险决定因素的相互作用。此外，研究的特殊部分涉及体力活动、职业因素和家庭化学品暴露的影响。在体力活动方面，特别努力改进暴露评估，要求妇女佩戴加速计，以获得比单纯面谈数据更客观的测量结果。该研究还涉及组织样本的收集，以实现精确的肿瘤分类以及肿瘤生物标志物的测定（包括利用新开发的组织微阵列技术）。在这次调查中收集的大量数据使一些分析成为可能。关于乳腺癌，目前正在进行分析，以评估职业暴露的影响，体力活动水平，人体测量因素，围产期暴露，以及肿瘤分期和激素受体状态的病因异质性，另一个大型病例对照研究，重点是乳腺癌，涉及收集颊细胞标本。这项工作需要进行大量的方法学工作，以确定收集、处理和储存样本的最佳方式，从而最大限度地提高DNA产量。乳腺癌的风险也是一个主要的兴趣，在后续的妇女队列先前筛选骨密度。这一资源，以前包括收集血清学样本，目前正在收集口腔拭子，将能够评估骨密度，遗传因素和内源性激素在预测随后的癌症发生的相互关系。最近与妇科肿瘤组建立了合作，以确定在一些正在进行的试验的背景下收集流行病学数据的方法。一个标准化的调查问卷已经开发出来，并已被纳入一个大型的子宫内膜试验。这项工作应该是有用的，在评估流行病学预测和分子标记物与仔细定义的组织学亚组的肿瘤。希望该问卷可以整合到其他癌症部位的试验中，并且可以开发其他更具针对性的问卷，以解决妇科肿瘤学家感兴趣的特定假设。我们已经了解了很多关于宫颈癌的自然史（如另一个项目报告所述），现在急于扩大我们在这一领域的知识，以解决另一个妇科肿瘤，即子宫内膜癌的自然史。子宫内膜增生被认为会增加子宫内膜癌的后续风险，但缺乏准确预测风险的数据，并且尚不清楚其他因素如何影响这些风险。我们正在预付健康计划内进行巢式病例对照研究，以更好地了解诊断为子宫内膜增生的妇女患子宫内膜癌的风险。这项研究的结果有可能改善高危妇女的临床管理，并启发对子宫内膜激素致癌作用的理解。我们还处于开发一项研究的试点阶段，以评估可能对卵巢癌和子宫内膜癌的发展很重要的早期标志物。