Hormone-Related Cancers

该项目涵盖了广泛的研究基础，旨在评估大多数与激素相关的癌症的流行病学。针对乳腺癌、子宫内膜癌、卵巢癌和睾丸癌的重大努力正在进行中。我们也有一个关于前列腺癌的积极研究计划，在另一份报告中涉及(Z01 CP010180-02)。我们为所有这些癌症所做的努力与各种环境、遗传和激素风险预测因素有关。波兰已经完成了一项大型的多学科研究，以评估乳腺癌、卵巢癌和子宫内膜癌的风险因素。这项研究涉及收集多个生物样本，主要目的是评估风险的遗传和环境决定因素的相互影响。此外，研究的特殊部分涉及身体活动、职业因素和家庭化学暴露的影响。在体力活动方面，特别努力改进暴露评估，要求妇女佩戴加速度计，以获得比单独采访数据更客观的衡量标准。这项研究还包括收集组织样本，以实现准确的肿瘤分类以及肿瘤生物标志物的分析(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许多分析成为可能。关于乳腺癌，目前正在进行分析，以评估职业暴露、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的影响。另一项以乳腺癌为重点的大型病例对照研究收集了口腔细胞样本。这项工作需要广泛的方法学工作，以确定收集、处理和储存样本的最佳手段，以最大限度地提高DNA产量。乳腺癌风险也是之前对一组女性进行骨密度筛查的主要兴趣所在。这一资源以前涉及血清样本的收集，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之间的相互关系，以预测随后的癌症发生。最近与妇科肿瘤学小组建立了合作关系，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。一个标准化的问卷已经被开发出来，并被整合到一项关于子宫内膜的大型试验中。这项工作在评估流行病学预测指标和与仔细定义的肿瘤组织学亚型相关的分子标记方面应该是有用的。希望这份问卷可以整合到其他癌症部位的试验中，并开发更多更有针对性的问卷，以解决妇科肿瘤学家感兴趣的特定假设。我们已经了解了许多宫颈癌的自然历史(如另一个项目报告中所述)，现在急于扩大我们在这一领域的知识，以解决另一种妇科肿瘤的自然历史，即子宫内膜癌。子宫内膜增生症被认为会增加随后发生子宫内膜癌的风险，但缺乏准确预测风险的数据，也不清楚其他因素可能如何影响这些风险。我们正在进行一项预付费健康计划中的嵌套病例对照研究，以更好地了解被诊断为子宫内膜增生症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治疗，并启发人们对子宫内膜激素致癌的理解。我们还处于开发一项评估早期标志物的研究的试点阶段，这些标志物可能对卵巢癌和子宫内膜癌的发展至关重要。

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.