Therapeutic and Diagnostic Factors as Related to Cancer

该项目的一个主要重点是确定外源性激素与随后的癌症风险的关系。使用与检查外源性激素对乳腺癌风险的影响相似的方法，在大型筛查项目的背景下进行的分析显示，绝经期激素的使用与卵巢癌风险相关。这些分析表明，随着多年使用激素的风险增加，特别是当使用的制剂是无对抗性雌激素时。与乳腺癌的关系正在通过额外的随访数据进行研究。此外，正在进行分析，以澄清肿瘤亚组（如激素受体状态定义的亚组）之间的关系。与其他肿瘤部位（包括子宫内膜癌和肺癌）的关系也在研究中。在几个病例对照研究的背景下，我们也追求与激素替代疗法的关系。最新的分析显示，一些证据表明，激素的使用可能会增加宫颈腺癌的风险，而鳞状细胞肿瘤没有关系。这种差异实际上支持了这样的观点，即与宫颈肿瘤相比，宫颈腺癌可能与子宫内膜更密切相关。 同样令人感兴趣的是乳房植入物与随后的癌症风险的关系。乳腺癌的风险一直令人担忧，因为乳房植入物可能会干扰乳房X光检查病灶的可视化。然而，在我们进行的一项大型回顾性研究中，我们没有发现乳腺癌风险改变的证据。这些患者的其他癌症部位通常也没有发生变化，尽管观察到肺癌和脑癌的风险升高，但其解释仍不清楚。在死亡率分析中，植入患者自杀死亡的风险显著升高，但其他死亡原因与一般人群相似。目前正在进行与乳房植入体相关的结缔组织疾病风险分析。此外，我们将继续跟踪死亡率队列，以确定先前观察到的模式是否持续存在。 还正在进行一项回顾性队列研究，以检查不同不孕原因和不同相关疗法对癌症风险的影响。特别值得关注的是，使用促排卵药物是否易患卵巢癌。这项研究涉及到对早在20世纪60年代就被诊断出的患者的医疗记录的详细提取，以及对获得的最新健康信息的问卷调查的管理。这项研究的一个优点是收集了有关不孕症原因的详细信息。这将有助于分析特定的内分泌异常与癌症风险的关系。在与丹麦的研究者合作进行的另一项调查中，评估了使用促排卵药物受孕的儿童患癌症的风险。初步分析显示，儿童癌症风险没有改变。 许多医学状况被认为是乳腺癌、子宫内膜癌和卵巢癌的易感因素，但这些研究中的大多数都依赖于患者对这些既往疾病的报告。为了获得关于这些既往疾病性质的更准确信息，我们在丹麦进行了一项大型病例队列研究，该研究涉及访问医疗记录中包含的疾病详情。正在进行的分析正在根据先前诊断的细节评估癌症风险的关系。

A major emphasis of this project has been to define the relationship of exogenous hormones to subsequent cancer risk. Using a similar approach as had been used to examine the effects of exogenous hormones on breast cancer risk, analyses within the context of a large screening program showed an association of menopausal hormone use with the risk of ovarian cancer. These analyses showed risk to increase with years of use of hormones, particularly when the preparation used was unopposed estrogens. Relationships with breast cancer are being pursued with additional follow-up data. In addition, analyses are ongoing to clarify relationships for subgroups of tumors (such as those defined by hormone receptor status). Relationships with other tumor sites (including endometrial and lung cancers) are also being pursued. Within the context of several case-control studies we have also pursued relationships with hormone replacement therapy. The latest analyses showed some evidence that hormone use might increase the risk of cervical adenocarcinomas, whereas no relationship was seen for squamous cell tumors. This variation in effect supported the notion that cervical adenocarcinomas might be more closely linked to endometrial as contrasted with cervical tumors. Also of interest is the relationship of breast implants to subsequent cancer risk. Breast cancer risk has been of concern, given that breast implants can interfere with the mammographic visualization of lesions. However, in a large retrospective study that we conducted, we found no evidence for an alteration in breast cancer risk. These patients also generally did not experience alterations in other cancer sites, although elevations were observed in the risk of lung and brain cancers, the explanation for which remains unclear. In a mortality analysis, implant patients had signficantly elevated risks of death from suicide, but other causes of death were similar to the general population. Currently underway are analyses of risk of connective tissue diseases related to breast implants. In addition, we are continuing to follow the cohort for mortality to determine whether previously observed patterns persist. A retrospective cohort study is also being conducted to examine the effects on cancer risk of different causes of infertility and of different associated therapies. Of particular concern is whether the use of ovulation stimulating drugs predisposes to ovarian cancer. This study involves detailed abstraction of medical records of patients diagnosed as long ago as the 1960's and administration of questionnaires to obtained updated health information. A strength of the study is the detailed information collected on causes of infertility. This will enable analyses related to how specific endocrinologic abnormalities might relate to cancer risk. In a separate investigation, conducted in collaboration with investigators in Denmark, cancer risk among children conceived following use of ovulation-stimulating drugs has been assessed. Preliminary analyses show no alteration in childhood cancer risk. A number of medical conditions have been suggested as predisposing to the risk of breast, endometrial and ovarian cancers, but most of these studies have relied on patients reports of these prior conditions. To obtain more precise information on the nature of these prior medical conditions, we have conducted a large case-cohort study in Denmark that involves access to details of the conditions as contained in medical records. Ongoing analyses are assessing relationships of cancer risk according to details of the prior diagnoses.