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: 8565423
• 负责人: LOUISE BRINTON
• 金额: $ 91.72万
• 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/8565423
• 关键词: Accounting; Affect; Alendronate; Anti-Inflammatory Agents; Anti-inflammatory; Benign; Bone Density; Breast Cancer Risk Factor; Cholesterol; Clinical; Clinical Trials; Cohort Studies; Data; Development; Diabetes Mellitus; Diagnostic Factor; Diet; Drug usage; Endometrial Carcinoma; Estrogen Therapy; Estrogen receptor positive; Estrogens; Etiology; Evaluation; Family; Fibroid Tumor; Fracture; Gynecologic; Health; Histology; Hormones; Hypertension; Infertility; Inflammation; Intervention; Investigation; Joints; Link; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of testis; Medical; Menopause; Outcome; Participant; Pharmaceutical Preparations; Physical activity; Postmenopause; Preparation; Progestin Therapy; Progestins; Recording of previous events; Research; Risk; Risk Factors; Role; Sampling Studies; Serological; Severities; Stress; Suggestion; Therapeutic; Therapeutic Intervention; Thyroid Diseases; Time; United States National Institutes of Health; Uterus; Woman; bone; bone loss; cancer risk; cancer site; cohort; diabetic; endometriosis; follow-up; hormone therapy; hypertension treatment; interest; malignant breast neoplasm; prospective; tumor; volunteer

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 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. In fact, we found evidence that women who used progestins sequentially, particularly for long periods of time, might be at an increased risk of developing endometrial cancer compared to non-users. 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. In contrast to the relationships observed for breast and gynecologic cancers, we observed no relationship of hormone therapy to lung cancer risk, as had been suggested by some earlier studies. The AARP study has also been useful for evaluating effects on cancer risk of other medications. Analyses have assessed breast, endometrial and liver cancer risk in relation to non-steroidal anti-inflammatory drugs (NSAIDs), stimulated by some research that has suggested an important role for inflammation in the etiology of these cancer sites. There were suggestions for all three of these cancer site that NSAID use might reduce risk, although the relationships with the drugs used were somewhat different across cancer sites. We are also evaluating risk of testicular cancer in relation to certain cholesterol-lowering and diabetic 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 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.

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。最近的分析利用我们大型前瞻性队列研究的数据评估了绝经期激素与妇科和乳腺癌风险的关系。利用美国国立卫生研究院-美国退休人员协会饮食与健康队列研究的数据，我们澄清了一些关于使用绝经期激素治疗的妇女患卵巢癌风险的未解决问题。使用无对抗性雌激素治疗10年或以上的妇女患卵巢癌的风险增加，这进一步证明了绝经后雌激素水平升高会影响卵巢癌发展的假设。此外，这项研究首次提供了一些强有力的证据，明确地将雌激素和黄体酮的使用与子宫完整的女性患卵巢癌的风险增加联系起来。这些结果重申了对现有队列进行长期随访的价值，以阐明接受更年期激素治疗的妇女患卵巢癌等罕见结局的风险增加。这项大型队列研究也被用于评估绝经期激素与子宫内膜癌风险的关系。与之前的一些建议相反，雌激素加黄体酮治疗可能预防这种癌症，我们没有发现这种保护的证据。事实上，我们发现有证据表明，连续使用黄体酮的女性，特别是长时间使用黄体酮的女性，与不使用黄体酮的女性相比，患子宫内膜癌的风险可能更高。此外，在同一项研究中，我们研究了单独使用雌激素和联合使用雌激素-黄体酮治疗与乳腺癌风险的关系。这项调查发现两种制剂的风险都升高，尽管联合治疗的相关性更强。激素对苗条女性的影响更大，但即使在肥胖女性中，联合治疗仍然是一个危险因素。最后，数据被用来评估激素是否对不同类型的肿瘤有不同的关系。雌激素受体阳性的肿瘤效果最强，这些关系影响其他临床参数，包括组织学。这些分析强调了在评估激素作用时考虑关节临床参数的重要性。与观察到的乳腺癌和妇科癌症的关系相反，我们没有观察到激素治疗与肺癌风险的关系，正如一些早期研究所表明的那样。美国退休人员协会的研究也有助于评估其他药物对癌症风险的影响。一些研究表明，炎症在这些癌症部位的病因学中起着重要作用，这些研究对非甾体抗炎药（NSAIDs）与乳腺癌、子宫内膜癌和肝癌的风险进行了评估。尽管在不同的癌症部位，使用非甾体抗炎药与所使用的药物之间的关系有所不同，但对于这三种癌症部位，都有使用非甾体抗炎药可能降低风险的建议。我们也在评估睾丸癌风险与某些降胆固醇和糖尿病药物的关系。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。骨质流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、身体活动和外源性激素）在多大程度上改变了与骨密度的关系尚不清楚。为了详细说明这些研究问题，我们对两万多名绝经后妇女进行了一项后续研究，这些妇女自愿参加了骨骼增强药物阿仑膦酸钠的临床试验。这一大型队列包括了关于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影响的理想选择。研究参与者的血清学样本的可用性也将有助于评估内源性激素和骨矿物质密度对随后乳腺癌风险的相互作用。