Hormone-Related Cancers

该项目涵盖了广泛的研究基础，旨在评估大多数激素相关癌症的流行病学。目前正在对乳腺癌、子宫内膜癌、卵巢癌和睾丸癌进行重大努力。我们也有一个活跃的前列腺癌研究项目，在单独的报告（Z01 CP010180-02）中有涉及。我们对所有这些癌症的研究都与各种环境、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。这项研究收集了多种生物样本，主要目的是评估遗传和环境因素对风险的相互影响。此外，该研究的特殊组成部分探讨了身体活动、职业因素和家庭化学品暴露的影响。对于体力活动，特别努力改进暴露评估，要求妇女佩戴加速度计，以获得比单独面谈数据更客观的测量。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）。在这项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、身体活动水平、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。另一项针对乳腺癌的大型病例对照研究收集了口腔细胞标本。这项工作需要大量的方法学工作，以确定收集、处理和储存样品的最佳方法，以最大限度地提高DNA产量。乳腺癌的风险也是对先前进行骨密度筛查的一组妇女进行随访的主要兴趣。该资源以前涉及血清学样本的收集，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在预测随后的癌症发生方面的相互关系。最近与妇科肿瘤学组建立了合作，以确定在一些正在进行的试验中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，并已纳入子宫内膜的大型试验。这项工作应该有助于评估与仔细定义的肿瘤组织学亚群相关的流行病学预测因子和分子标记。希望该问卷可以整合到其他癌症部位的试验中，并且可以开发更多有针对性的问卷来解决妇科肿瘤学家感兴趣的特定假设。我们已经了解了宫颈癌的自然史（如另一份项目报告所述），现在迫切希望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史，即子宫内膜癌。子宫内膜增生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，也不清楚其他因素如何影响这些风险。我们正在预付费健康计划中进行一项巢式病例对照研究，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。本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癌变的理解。我们还在开展一项研究的试点阶段，以评估可能对卵巢癌和子宫内膜癌发展很重要的早期标志物。

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.