Hormone-Related Cancers

激素相关癌症

• 批准号: 8349560
• 负责人: LOUISE BRINTON
• 金额: $ 275.29万
• 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/8349560
• 关键词: Address; Adult; African; African American; Age; American; Area; Attention; Atypical hyperplasia; Biological Markers; Biopsy; Bone Density; Breast; Breast Cancer Risk Factor; Case-Control Studies; Caucasians; Caucasoid Race; Characteristics; Chemical Exposure; Chlordan; Clinical; Collaborations; Collection; Colorectal Cancer; Complement; Consumption; Cryptorchidism; Dairy Products; Data; Department of Defense; Development; Diagnosis; Diagnostic; Disease; Endogenous Factors; Endometrial Carcinoma; Endometrial Hyperplasia; Epidemiology; Estrogen receptor negative; Estrogens; Etiology; Exhibits; Exposure to; Female Genital Neoplasms; Follow-Up Studies; Funding; Genetic; Genetic Polymorphism; Ghana; Gonadotropins; Gynecologic Oncology Group; Height; Heterogeneity; High Prevalence; Histologic; Hormonal; Hormones; Household; Immunohistochemistry; Immunologics; Incidence; Investigation; Knowledge; Laboratories; Learning; Liquid Chromatography; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Malignant neoplasm of testis; Mammographic Density; Measures; Missouri; Molecular Classification of Tumors; Natural History; Nested Case-Control Study; Occupational; Participant; Pathway interactions; Phase; Physical activity; Poland; Polishes; Population; Pregnancy; Prepaid Health Plans; Prevalence; Puberty; Publications; Questionnaires; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sales; Sampling; Serological; Serum; Site; Somatomedins; Subgroup; Techniques; Time; Tissue Microarray; Tissue Sample; Tumor Tissue; Universities; Vermont; Woman; Women' s Group; Women' s Health; adiponectin; aged; base; cancer risk; cancer type; cohort; design; epidemiologic data; follow-up; hormone related cancer; improved; inhibin; interest; malignant breast neoplasm; maternal cigarette smoking; men; molecular marker; novel; organochlorine pesticide; outcome forecast; programs; tumor; urinary

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, ovarian and endometrial cancers. 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 via having women wear accelerometers. 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 has enabled a number of analyses. With respect to breast cancer, recent publications have evaluated effects of genetic polymorphisms and etiologic heterogeneity by tumor tissue markers. 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. It is well recognized that breast cancers that occur among Africans and African-Americans tend to exhibit different clinical characteristics as compared with Caucasians, incluidng a higher prevalence of estrogen receptor negative and triple negative tumors, cancers associated with a generally poor prognosis. To better understand the reasons for the occurrence of these cancers, we are developing plans to undertake a case-control study in Ghana, where incidence rates of breast cancer have been increasing. The study is being designed to evaluate some novel etiologic hypotheses as well as to relate risk factors to carefully defined subtypes of breast cancers. 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 supported 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 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. 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. 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. 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. We have used a newly developed technique at a laboratory in Frederick that uses liquid chromatography/mass spectometry to measure 16 estrogens and their metabolites. We are also measuring the estrogenpanel in our BFIT followup study, which will allow us an opportunity to examine the interrelationships between estrogens and measured bone density as they relate to subsequent risk of breast, colorectal, endometrial and ovarian cancers. We are also currently collaborating with investigators of the Womens Health Initiative to measure estrogens in relation to ovarian and endometrial cancers that developed among participants in the observational component of that investigation. Finally, in the Polish study we are measuring urinary estrogens among the control subjects in order to more fully understand relationships with identified risk factors, including physical activity levels that have been objectively determined.

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。针对乳腺癌、子宫内膜癌、卵巢癌和睾丸癌的主要努力正在进行中。我们还有一个关于前列腺癌的积极研究计划，在一份单独的报告 (Z01 CP010180-02) 中进行了介绍。我们针对所有这些癌症所做的努力都与各种环境、遗传和激素风险预测因素有关。 2000 年至 2004 年间，波兰进行了一项大型多学科研究，评估乳腺癌、卵巢癌和子宫内膜癌的危险因素。该研究涉及收集多个生物样本，主要目的是评估生物标志物与风险的关联以及风险的遗传和环境决定因素的相互作用。此外，该研究的特殊部分还涉及体力活动、职业因素和家用化学品接触的影响。对于体育活动，我们特别努力通过让女性佩戴加速计来改善暴露评估。该研究还涉及收集组织样本以进行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）。收集的大量数据使得许多分析成为可能。关于乳腺癌，最近的出版物通过肿瘤组织标志物评估了遗传多态性和病因异质性的影响。对之前接受骨密度筛查的一组女性进行的随访中，乳腺癌风险也引起了人们的主要兴趣。该资源之前涉及收集血清学样本和详细的问卷数据，将能够评估骨密度、遗传因素和内源性激素之间的相互关系，以预测随后的癌症发生。众所周知，与白种人相比，非洲人和非裔美国人中发生的乳腺癌往往表现出不同的临床特征，包括雌激素受体阴性和三阴性肿瘤的患病率较高，这些癌症通常预后不良。为了更好地了解这些癌症发生的原因，我们正在制定计划，在乳腺癌发病率不断上升的加纳进行病例对照研究。该研究旨在评估一些新的病因学假设，并将危险因素与仔细定义的乳腺癌亚型联系起来。乳房X线密度已被认为是后续乳腺癌风险的主要预测因素，但这种关联的生物学基础尚不清楚。通过销售乳腺癌邮票获得的资金支持了一项研究，该研究旨在评估佛蒙特大学接受乳腺活检的一组妇女的乳房X线照相密度的激素和免疫相关性。已与妇科肿瘤学组建立合作，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方法。标准化问卷已经开发出来并纳入子宫内膜癌的大型试验中。这项工作应该有助于评估与仔细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。我们已经了解了很多关于宫颈癌的自然史（如另一个项目报告中所述），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（即子宫内膜癌）的自然史。子宫内膜增生被认为会增加随后患子宫内膜癌的风险，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。我们在预付费健康计划中进行了一项巢式病例对照研究，以更好地了解被诊断患有子宫内膜增生的女性患子宫内膜癌的风险。这项研究的数据支持了非典型增生与随后的子宫内膜癌风险密切相关的观点。我们还处于开展一项研究的试点阶段，该研究旨在评估对卵巢癌和子宫内膜癌的发展可能很重要的早期标志物。睾丸癌是 15-35 岁美国男性中最常见的癌症类型，白人男性的发病率是黑人男性的五倍。为了研究这种肿瘤的病因，我们与美国国防部 (DoD) 合作对美国军人进行了一项大型病例对照研究。对诊断前血清样本的分析发现，接触有机氯农药（特别是二氯二苯基二氯乙烯 (DDE) 和氯丹）与睾丸癌显着相关。血清分析还发现，患有睾丸癌的男性在诊断前具有异常的促性腺激素水平。其他研究结果表明，虽然成年身高与风险相关，但青春期年龄、乳制品消费和母亲怀孕期间吸烟无关。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。然而，抑制素途径的遗传变异可能与之相关。作为这项研究的补充，其他研究也正在进行中，以确定隐睾症的根本原因，隐睾症是睾丸癌公认的危险因素。这些研究比较了黑人和白人群体中隐睾的患病率以及该异常的危险因素。尽管隐睾症的患病率在白人中明显较高，但隐睾率的微小差异与睾丸癌风险的巨大差异并不相符。两组之间的危险因素差异不大，母体激素水平的差异与隐睾无关。该项目还重点关注内源激素对多种肿瘤部位的病因作用。在这些研究中，人们的注意力不仅集中在传统上接受的激素上，还集中在一些新提出的预测因子上，包括脂联素水平。对梅奥血清库密苏里州哥伦比亚部分的参与者进行了长期跟踪。我们在弗雷德里克的一个实验室使用了一项新开发的技术，该技术使用液相色谱/质谱法来测量 16 种雌激素及其代谢物。我们还在 BFIT 随访研究中测量雌激素组合，这将使我们有机会检查雌激素和测量的骨密度之间的相互关系，因为它们与随后患乳腺癌、结直肠癌、子宫内膜癌和卵巢癌的风险有关。我们目前还与妇女健康倡议的研究人员合作，测量与该调查观察部分参与者中发生的卵巢癌和子宫内膜癌相关的雌激素。最后，在波兰的研究中，我们测量了对照受试者的尿雌激素，以便更全面地了解与已确定的危险因素的关系，包括客观确定的体力活动水平。