Therapeutic and Diagnostic Factors as Related to Cancer Risk

与癌症风险相关的治疗和诊断因素

• 批准号: 8157916
• 负责人: LOUISE BRINTON
• 金额: $ 69.51万
• 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/8157916
• 关键词: Diagnostic Factor; Therapeutic; cancer risk

A major emphasis of this project has been to define the relationship of exogenous hormones to subsequent cancer risk. Recent analyses have assesed the relationships of menopausal hormones to gynecologic and breast cancer risk using data from our large, prospective cohort studies. Using data from the NIH-AARP Diet and Health Cohort Study, we have clarified some unresolved issues regarding ovarian cancer risk in women who use menopausal hormone therapy. Increased ovarian cancer risks among women who used unopposed estrogen therapy for 10 or more years provide further evidence to support the hypothesis that increased estrogen levels after menopause can influence the development of ovarian cancer. In addition, this study provided some of the first strong evidence that specifically links estrogen plus progestin use to increased ovarian cancer risk in women with intact uteri. These results reiterate the value of long-term follow-up of existing cohorts to elucidate increased risks of rare outcomes, such as ovarian cancer, among women who exposed to menopausal hormone therapy. This large cohort study has also been used to assess relationships of menopausal hormones to the risk of endometrial cancers. In contrast to some previous suggestions that estrogen plus progestin therapy might protect against this cancer, we found no evidence for such protection. Of note was that neither continuous nor sequential estrogen plus progestin were found to have any statistically significant associations with endometrial cancer risk in this population. Further, within this same study we examined risks of breast cancer related to both estrogens alone and with combined estrogen-progestin therapy. This investigation found elevated risks for both types of preparations, although combined therapy was more strongly related. Hormone effects were stronger among thin women, but combined therapy continued to be a risk factor even among heavy women. Finally, data were used to assess whether hormones had differential relationships on different types of tumors. The strongest effects were seen for estrogen receptor positive tumors, and these relations affected other clinical parameters, including histology. These analyses stressed the importance of considering joint clinical parameters when assessing hormone effects.The AARP study has also been useful for evaluating effects on cancer risk of other medications. Analyses have also assessed breast cancer risk in relation to non-steroidal anti-inflammatory medications. This area of research has been of interest given that inflammation has been proposed as being involved as an etiologic agent for this cancer site. These analyses showed evidence of reduced risk associated with aspirin use, particularly for estrogen receptor positive cancers. We are also evaluating effects on breast cancer risk of certain medications used in the treatment of cardiovascular diseases that are known to have demethylating effects on DNA.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 have conducted 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 availability of serologic samples from study participants will also enable assessment of the interactive effects of endogenous hormones and bone mineral density on subsequent breast cancer risk.

该项目的主要重点是定义外源激素与随后的癌症风险的关系。最近的分析已经通过我们大型前瞻性队列研究的数据来解决了更年期激素与妇科和乳腺癌风险的关系。使用NIH-AARP饮食和健康队列研究中的数据，我们阐明了使用更年期激素治疗的女性卵巢癌风险的一些未解决的问题。使用无反对雌激素疗法的妇女中卵巢癌的风险增加了10年或更长时间，提供了进一步的证据，以支持以下假设：更年期后雌激素水平提高会影响卵巢癌的发展。此外，这项研究提供了一些第一个有力的证据，这些证据专门将雌激素加孕激素使用以增加完整子宫女性的卵巢癌风险。这些结果重申了现有队列的长期随访的价值，以阐明暴露于更年期激素治疗的妇女中罕见结果的增加，例如卵巢癌。这项大型队列研究还用于评估更年期激素的关系，以使子宫内膜癌的风险。与以前有关雌激素加孕激素治疗可能预防这种癌症的一些建议相反，我们没有发现这种保护的证据。值得注意的是，在该人群中，未发现连续和顺序雌激素加孕激素与子宫内膜癌的风险具有任何统计学意义。此外，在这项研究中，我们检查了单独使用雌激素和雌激素 - 原生蛋白疗法的乳腺癌风险。这项调查发现，两种制剂的风险升高，尽管联合治疗的相关性更强。瘦女性中的激素作用更强，但即使在沉重的女性中，联合治疗也是危险因素。最后，使用数据来评估激素是否在不同类型的肿瘤上具有不同的关系。雌激素受体阳性肿瘤的影响最强，这些关系影响了其他临床参数，包括组织学。这些分析强调了在评估激素效应时考虑联合临床参数的重要性。AARP研究也可用于评估对其他药物癌症风险的影响。分析还评估了与非甾体类抗炎药有关的乳腺癌风险。鉴于已提出炎症是作为该癌症部位的病因学剂所参与的，因此这一研究领域引起了人们的关注。这些分析表明，与使用阿司匹林相关的风险降低的证据，特别是对于雌激素受体阳性癌症。我们还正在评估对乳腺癌的影响，用于治疗心血管疾病的某些药物的风险，这些药物已知对DNA具有脱甲基作用。当时的队列研究表明，骨折病史或低骨矿物质密度的女性中乳腺癌的风险降低。尚未研究骨损失对骨质损失的严重程度和时机的影响，以及其他风险因素（家族病史，人体测量因素，体育活动和外源激素）在多大程度上改变了与骨密度的关系。为了详细说明这些研究问题，我们已经对20,000多名绝经后妇女进行了后续研究，这些妇女自愿参加了骨增强药物的临床试验。这个大型队列包括有关主要乳腺癌危险因素的广泛基线信息，因此是评估与骨矿物质密度的潜在相互作用以及骨矿物质密度对其他癌症部位的影响的理想选择。研究参与者的血清学样本的可用性还将评估内源激素和骨矿物质密度对随后的乳腺癌风险的相互作用。