Therapeutic & Diagnostic Factors Related to Cancer RisK

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。研究评估了口服避孕药和更年期激素的效果。鉴于之前的调查显示，年轻女性最近使用口服避孕药导致乳腺癌风险过高，人们进一步关注风险上升是否可归因于使用某些药片。这在一定程度上支持了服用含有高剂量雌激素或孕激素的药片的高风险。从乳腺癌检测示范项目参与者的后续研究数据中获得分析更年期激素影响的独特机会，这是一个全国性的大型乳房筛查项目。使用类似于以前乳腺癌风险分析的方法，额外的分析将外源性激素的使用与卵巢癌风险的增加相关联。这些分析表明，随着激素使用年限的增加，风险增加，特别是当使用的制剂是非对立雌激素时。与子宫内膜癌的关系正在通过更多的随访数据进行追踪。 同样令人感兴趣的是隆胸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病变的乳房X光摄影。然而，在我们进行的一项大型回顾研究中，我们没有发现乳腺癌风险发生变化的证据。这些患者通常也没有经历其他癌症部位的变化，尽管在肺癌和脑癌的风险中观察到了升高，其原因尚不清楚。在一项死亡率分析中，植入患者自杀死亡的风险显著增加，但其他死亡原因与普通人群相似。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。此外，我们正在继续跟踪死亡率队列，以确定之前观察到的模式是否持续。 还进行了一项回溯性队列研究，以检查不同不孕症原因和不同相关疗法对癌症风险的影响。这项研究包括对早在20世纪60年代的S确诊的患者的病历进行详细提取，并通过问卷调查获得最新的健康信息。这项研究的一个优势是收集了关于不孕不育原因的详细信息。分析表明，不孕症类型(原发与继发)是癌症风险的更重要的预测因素，而不是特定的不孕原因。然而，子宫内膜异位症患者患卵巢癌的风险特别高。总体而言，这项研究提供了关于使用促排卵药物的令人放心的结果，表明使用克罗米芬或人类绝经期促性腺激素没有显著增加癌症风险。然而，在跟踪时间最长的受试者(15年或20年以上)中，乳腺癌和卵巢癌的风险都略有增加，这支持了对这些药物的长期影响进行额外监测的必要性。不同的兴趣还集中在促排卵药物是否会影响使用该药物后怀孕的儿童患癌症的风险。在丹麦的另一项调查中，使用了创纪录的联系努力，提供了总体上令人放心的结果。唯一显示出任何变化的癌症部位是发生在生命后期的造血癌。然而，这个肿瘤部位的风险增加是基于少数人，并不显著，而且似乎更多地与使用的潜在原因有关，而不是药物的效果。 最近的队列研究表明，有骨折史或骨密度低的女性患乳腺癌的风险降低。骨丢失的严重程度和时间对风险的影响尚未被调查，其他风险因素(家族史、人体测量因素、体力活动和外源性激素)改变与骨密度的关系的程度尚不清楚。为了详细说明这些研究问题，我们正在对20,000多名绝经后妇女进行跟踪研究，她们自愿参加骨增强药物阿仑磷酸钠的临床试验。这一庞大的队列包括关于主要乳腺癌风险因素的广泛基线信息，因此是评估与骨密度的潜在交互作用以及骨密度对其他癌症部位影响的理想选择。这项研究的数据收集阶段已接近完成，计划中的分析将回答有关绝经后女性骨密度与癌症风险之间关系的重要问题。 许多医疗条件被认为是乳腺癌、子宫内膜癌和卵巢癌风险的诱因，但这些研究中的大多数都依赖于患者对这些既往疾病的报告。为了更准确地了解这些既往疾病的性质，我们在丹麦进行了一项大型病例队列研究，其中包括查阅医疗记录中包含的条件的详细信息。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. Studies have assessed effects of both oral contraceptives and menopausal hormones. Given previous investigations that have shown excess risks of breast cancer associated with recent use of oral contraceptives among young women, further attention has focused on whether the elevations in risk were attributable to use of certain pills. This showed some support for higher risks among users of pills containing high doses of estrogens or progestins. Unique opportunities for analyzing effects of menopausal hormones derived from data from the follow-up study of participants in the Breast Cancer Detections Demonstration Project, a large nation-wide breast screening project. Using approaches similar to previous analyses for breast cancer risk, additional analyses related use of exogenous hormones to an elevated 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 endometrial cancer are being pursued with additional follow-up data. 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 was also conducted to examine the effects on cancer risk of different causes of infertility and of different associated therapies. This study involved 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 was the detailed information collected on causes of infertility. Analyses showed that type of infertility (primary vs. secondary) was a more important predictor of cancer risk than specific causes of infertility. However, patients with endometriosis were at an especially high risk of developing ovarian cancer. In general, the study provided reassuring results regarding use of ovulation-inducing agents, showing no major increases in cancer risk relating to use of either clomiphene citrate or human menopausal gonadotropins. There were, however, slight increases in risk of both breast and ovarian cancers among the subjects followed for the longest periods of time (15 or 20+ years), supporting the need for additional monitoring of long-term effects of these agents. Separate interest has also focused on whether ovulation-inducing agents might affect the risk of cancer in children conceived following thier use. In a separate investigation in Denmark, which used record linkage efforts, generally reassuring results were provided. The only cancer site that showed any alteration was that of hematopoietic cancers occurring later in life. The elevation in risk for this tumor site, however, was based on small numbers, was non-significant, and appeared to relate more to underlying reasons for usage than to an effect of the medications. Recent cohort studies demonstrated reduced breast cancer risks among women with a history of fractures or low bone mineral density. The impact of the severity and timing of bone loss on risk has not yet been investigated, and the extent to which other risk factors (family history, anthropometric factors, physical activity, and exogenous hormones) modify the relationship with bone density is unknown. To elaborate on these research questions, we are conducting a follow-up study of over 20,000 postmenopausal women who volunteered for a clinical trial of the bone-enhancing drug alendronate. This large cohort includes extensive baseline information on major breast cancer risk factors, and thus is ideal for evaluating potential interactions with bone mineral density and the effects of bone mineral density on other cancer sites. The data collection phase of the study is nearly complete, and planned analyses will answer important questions about the relationship between bone density and cancer risk in postmenopausal women. 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.