Therapeutic and Diagnostic Factors Related to Cancer

这个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。使用类似的方法来检查外源性激素对乳腺癌风险的影响，在一个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的风险有关。这些分析表明，使用激素的风险随着使用时间的增加而增加，特别是当使用的制剂是无对抗的雌激素时。与乳腺癌的关系正在通过额外的随访数据进行研究。此外，正在进行分析以阐明肿瘤亚群之间的关系（例如由激素受体状态定义的肿瘤）。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，我们也探讨了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子宫颈腺癌的风险，而与鳞状细胞瘤没有关系。这种效果上的差异支持了子宫颈腺癌与子宫颈肿瘤相比可能与子宫内膜关系更密切的观点。同样令人感兴趣的是隆胸与随后癌症风险的关系。考虑到乳房植入物会干扰乳房x线摄影对病变的显示，乳腺癌的风险一直备受关注。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。这些患者在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，其原因尚不清楚。在一项死亡率分析中，植入物患者死于自杀的风险显著升高，但其他死因与一般人群相似。目前正在进行与乳房植入物相关的结缔组织疾病风险分析。在与瑞典研究人员合作进行的一项研究中，我们试图确定缩胸手术后乳腺癌风险降低的原因。使用从医疗记录中提取的数据，我们显示了与乳腺组织切除量成反比的关系。目前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。这项研究包括对早在20世纪60年代诊断的患者的医疗记录进行详细的提取，并对问卷进行管理，以获得最新的健康信息。在与丹麦研究人员合作进行的另一项调查中，对使用促排卵药物后怀孕的儿童患癌症的风险进行了评估。初步分析显示，儿童患癌症的风险没有变化。许多疾病被认为是乳腺癌、子宫内膜癌和卵巢癌风险的诱因，但这些研究大多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医疗状况性质的更准确信息，我们正在丹麦进行一项大型病例队列研究，该研究涉及获取医疗记录中包含的病情细节。这项研究将能够根据先前诊断的细节对癌症风险进行全面评估。

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 a study conducted in collaboration with Swedish investigators, we sought to determine reasons for a reduced risk of breast cancer that has been observed following breast reduction operations. Using data abstracted from medical records, we showed that the inverse relationship was related to the amount of breast tissue removed. 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. 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 are conducting a large case-cohort study in Denmark that involves access to details of the conditions as contained in medical records. This study will enable a thorough assessment of cancer risk in relation to details of the prior diagnoses.