Hormone-Related Cancers

激素相关癌症

• 批准号: 8157914
• 负责人: LOUISE BRINTON
• 金额: $ 254.7万
• 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/8157914
• 关键词: hormone related cancer

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 cancer, endometrial cancer, ovarian cancer, and testicular cancer. 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 was conducted in Poland between 2000-2004 to assess risk factors for breast cancer, ovarian cancer and endometrial cancer. The study involved collection of multiple biologic samples, with a primary aim of assessing biomarker associations with risk and 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 histological and molecular tumor classification (e.g. utilizing tissue microarray techniques for immunohistochemistry analyses). The large amount of data collected in this investigation are enabling a number of analyses. With respect to breast cancer, recent publications have evaluated effects of genetic polymorphisms, occupational exposures, physical activity levels, 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. The focus of the case-control study is to evaluate associations between genetic polymorphisms and risk. 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 detailed questionnaire data, will enable an assessment of the interrelationship of bone density, genetic factors and endogenous hormones in predicting subsequent cancer occurrence.Mammographic density has been recognized as a major predictor of subsequent breast cancer risk, but the biologic basis for this association is unclear. Funds made available through the sale of breast cancer stamps are currently being used for a study to assess hormonal and immunologic correlates of mammographic density among a group of women receiving breast biopsies at the University of Vermont. A collaboration has 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 cancer. This effort should be useful in assessing epidemiologic predictors and molecular markers associated with carefully defined histologic subgroups of tumors. The questionnaire is also beginning to be integrated into other trials of other cancer sites; in addition, plans are underway to develop targeted questionnaires 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 have conducted a nested case-control study within a prepaid health plan to better understand the risk of endometrial cancer in women diagnosed with endometrial hyperplasia. Data from this study have supported that notion that atypical hyperplasia is strongly related to subsequent endometrial cancer risk. 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 cancer and endometrial cancer. This study involves the collection of ovarian and endometrial tissues from patients undergoing a variety of gynecologic conditions; tissue samples will be linked with epidemiologic data to determine markers which may correlate with the future occurrence of malignancies.Testicular cancer is the most common type of cancer among American men aged 15-35 years and occurs five times more frequently among white men than among black men. To study the etiology of this tumor, we have conducted a large case-control study of U.S. servicemen in collaboration with the U.S. Department of Defense (DoD). Analysis of pre-diagnostic serum samples has found that exposure to organochlorine pesticides (specifically, dichlorodiphenyldichloroethylene (DDE) and chlordane) is significantly associated with testicular cancer. Serum analyses have also found that men who develop testicular cancer have aberrant gonadotropin levels prior to diagnosis. Additional findings indicate that while adult height is associated with risk, age at puberty, consumption of dairy products and maternal smoking in pregnancy are not associated. In addition, genetic variability in the insulin-like growth factor pathway and the hormone metabolizing pathway does not appear to be related to risk. Genetic variability in the inhibin pathway, however, may be associated. As a complement to this research, other studies have being undertaken to identify underlying causes of cryptorchism, a recognized risk factor for testicular cancer. These studies have compared the prevalence of cryptorchism, as well as risk factors for the anomaly, between black and white populations. Though the prevalence of cryptorchism is significantly higher among white populations, the small difference in the rate is not compatible with the large difference in testicular cancer risk. Risk factors between the two groups do not vary greatly and differences in maternal hormone levels are not related to cryptorchism.This project has also included a focus on the etiologic role of endogenous hormones for a variety of tumor sites. In these studies, attention is focusing not only on classically accepted hormones, but also on some newly suggested predictors, including adiponectin levels. An extended follow-up of participants in the Columbia, Missouri component of the Mayo Serum Bank has been undertaken; this will allow us to expand upon previous findings and to address newly emerging etiologic hypotheses. This resource is unique in having collected multiple biologic samples over time, allowing an assessment of how hormone levels change as patients approach diagnosis.

该项目涵盖了旨在评估大多数荷尔蒙相关癌症的流行病学的广泛研究基础。乳腺癌，子宫内膜癌，卵巢癌和睾丸癌正在进行重大努力。我们还制定了有关前列腺癌的积极研究计划，该计划在单独的报告中涵盖（Z01 CP010180-02）。我们对所有这些癌症的努力涉及风险的各种环境，遗传和荷尔蒙预测指标。在2000 - 2004年之间，在波兰进行了大型多学科研究，以评估乳腺癌，卵巢癌和子宫内膜癌的危险因素。该研究涉及收集多种生物学样本，其主要目的是评估具有风险的生物标志物关联以及风险遗传和环境决定因素的互动效应。此外，该研究的特殊组成部分还解决了体育活动，职业因素和家庭化学暴露的影响。对于体育活动，花费了特殊的努力来改善暴露评估，而妇女被要求佩戴加速度计，以获得比单独的访谈数据更多的客观措施。该研究还涉及组织样品的收集以实现组织学和分子肿瘤分类（例如，利用组织微阵列技术进行免疫组织化学分析）。本研究中收集的大量数据正在实现许多分析。关于乳腺癌，最近的出版物评估了遗传多态性，职业暴露，体育活动水平，围产期暴露以及通过肿瘤期和激素受体状态的病因异质性。这项工作需要大量的方法论工作来确定收集，加工和存储样品的最佳手段，以最大程度地提高DNA产量。病例对照研究的重点是评估遗传多态性和风险之间的关联。乳腺癌的风险在对先前筛查骨密度的一系列女性的随访中也引起了重大兴趣。该资源先前涉及血清学样本和详细的问卷数据，将能够评估骨密度，遗传因素和内源激素的相互关系，以预测随后的癌症发生。目前正在使用乳腺癌邮票提供的资金用于一项研究，以评估佛蒙特大学接受乳房活检的一组妇女乳房X线摄影密度的激素和免疫学相关性。已经与妇科肿瘤学组建立了合作，以确定在许多正在进行的试验的背景下收集流行病学数据的手段。已经开发了一份标准化的问卷，并已融入了大型子宫内膜癌试验中。这项工作对于评估与精心定义的肿瘤组织学亚组相关的流行病学预测因子和分子标记应该有用。问卷也开始纳入其他癌症部位的其他试验。此外，正在制定针对性问卷的计划，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有关宫颈癌的自然史（如另一份项目报告中所述），现在急于扩大我们在该领域的知识，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的子宫内膜癌的风险，但是缺乏准确预测风险的数据，尚不清楚其他因素如何影响这些风险。我们在预付费健康计划中进行了一项嵌套的病例对照研究，以更好地了解被诊断为子宫内膜增生的女性子宫内膜癌的风险。这项研究的数据支持认为非典型增生与随后的子宫内膜癌风险密切相关。这项研究的结果有可能改善高危女性的临床管理，并启发对子宫内膜中激素癌变的理解。我们还处于开发一项研究以评估早期标志物的试点阶段，这可能对卵巢癌和子宫内膜癌的发展很重要。这项研究涉及从患有多种妇科疾病的患者中收集卵巢和子宫内膜组织。组织样本将与流行病学数据联系起来，以确定可能与未来发生恶性肿瘤相关的标记。细胞性癌症是15-35岁的美国男性中最常见的癌症类型，白人男性的频率是黑人男性的频率五倍。为了研究该肿瘤的病因，我们与美国国防部（DOD）合作进行了一项大型病例对照研究。诊断前血清样品的分析发现，暴露于有机氯农药（特定于二氯二苯二氯乙烯（DDE）和氯烷）与睾丸癌显着相关。血清分析还发现，诊断前患有睾丸癌的男性在诊断前具有异常的促性腺激素水平。其他发现表明，尽管成人身高与风险相关，青春期的年龄，乳制品的消费和怀孕的产妇吸烟无关。此外，胰岛素样生长因子途径和激素代谢途径的遗传变异似乎与风险无关。但是，抑制素途径中的遗传变异性可能是相关的。作为对这项研究的补充，已经进行了其他研究以识别隐秘主义的潜在原因，这是公认的睾丸癌危险因素。这些研究比较了黑人和白人人群之间的密码术的流行以及异常的风险因素。尽管白人人群的隐态流行率明显更高，但该速率的差异与睾丸癌风险的差异不兼容。两组之间的危险因素不大，母体激素水平的差异与密码术无关。该项目还关注内源激素在各种肿瘤部位的病因作用。在这些研究中，注意力不仅关注经典的激素，而且集中在一些新建议的预测因子上，包括脂联素水平。已经进行了哥伦比亚的参与者的扩大随访，已进行了蛋黄酱的密苏里州组成部分；这将使我们能够扩展以前的发现并解决新兴的病因学假设。随着时间的流逝，该资源在收集多个生物学样本的情况下是独一无二的，可以评估激素水平随着患者的诊断而变化。