Discovering and Characterizing Novel Pregnancy-Associated Cancers

发现和表征新的与妊娠相关的癌症

• 批准号: 9330818
• 负责人: Casey Crump
• 金额: $ 15万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-11 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330818
• 关键词: Age; Angiogenic Factor; Birth; Breast; Cause of Death; Cessation of life; Characteristics; Clinical Management; Cohort Studies; Colon; Colorectal; Counseling; Cutaneous Melanoma; Data; Diagnosis; Diagnostic; Disease; Embryo; Epidemiologist; Estrogens; Female; Fetal Growth; Future; Grant; Growth Factor; Histologic; Hormones; Immunosuppression; Immunosuppressive Agents; Incidence; Malignant Neoplasms; Outcome; Ovarian; Ovary; Pattern; Physicians; Population; Postpartum Period; Postpartum Women; Predisposition; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Pregnancy-Associated Plasma Protein-A; Pregnant Women; Preventive Intervention; Publishing; Rectal Melanoma; Registries; Research; Risk; Sample Size; Site; Somatomedins; Standardization; Sweden; Testing; Therapeutic Intervention; Time; United States National Institutes of Health; Universities; Vascular Endothelial Growth Factors; Vulnerable Populations; Woman; cancer diagnosis; cancer site; carcinogenicity; cohort; cost; cost efficient; data registry; fetal; follow-up; hazard; implantation; innovation; malignant breast neoplasm; melanoma; mortality; novel; outcome forecast; population based; reproductive; young mother; young woman

PROJECT SUMMARY/ABSTRACT Cancer is the second leading cause of death in women of reproductive age. Pregnancy-associated cancers (diagnosed during pregnancy or up to 5 years postpartum) are increasing, highly lethal, and particularly devastating because they occur in young mothers. Breast cancer is known to have higher incidence and mortality in women who have recently given birth compared with other young women. However, little is known about pregnancy-associated cancers at sites other than the breast, such as the ovary, colon/rectum, and melanoma of the skin, which are relatively common and lethal, yet rarely have been examined. Limited evidence suggests that ovarian, colorectal, and melanoma cancers may have higher incidence and poorer outcomes in pregnant or postpartum women than in other young women. The underlying mechanisms may involve pro-angiogenic factors required for embryonic implantation (e.g., vascular endothelial growth factor [VEGF]), immunosuppression to avoid fetal rejection, and high levels of hormones required for fetal growth (e.g., insulin-like growth [IGF] factors, estrogens, and pregnancy-associated plasma protein-A [PAPPA]). We hypothesize that due to the pro-carcinogenic effects of angiogenic, immunosuppressive, and growth factors, pregnancy and the postpartum period are associated with higher incidence and mortality of ovarian, colorectal, and melanoma cancers. We will test these hypotheses by conducting the largest and most comprehensive population-based cohort studies to date of incidence patterns, diagnostic characteristics, and mortality of these cancers in pregnant and postpartum women using data for the entire population of Sweden, including all ~3.0 million women of reproductive age (15 to 49 years) during 1973-2014. Sweden is the ideal setting for the proposed study because of the availability of nearly 100% complete birth, cancer, and death registry data for the entire population, affording the large sample sizes needed to examine pregnancy-associated cancers with good statistical power. Cancer incidence and mortality rates are similar in Sweden and the US, and have the same major underlying biologic mechanisms. Our specific aims are to: (1) determine the incidence, diagnostic characteristics, histologic subtypes, and time windows of susceptibility for pregnancy-associated ovarian, colorectal, and melanoma cancers; and (2) determine mortality for these pregnancy-associated cancers and their most common subtypes. The proposed research is significant and innovative because it will be the largest and most comprehensive studies to date to identify the incidence, diagnostic characteristics, and mortality of pregnancy-associated cancers. It will have high statistical power to determine whether or not pregnancy is associated with increases in ovarian, colorectal, and melanoma cancers, and poorer outcomes in this understudied population of young mothers, as we hypothesize. The results will advance our understanding of pregnancy-associated cancers, inform clinical management and counseling, and guide future studies of other cancer sites and preventive or therapeutic interventions to reduce cancer incidence and mortality in women.

项目摘要/摘要 癌症是育龄妇女的第二大死因。妊娠相关癌症 (在怀孕期间或产后5年内确诊)正在增加，具有高度致命性，尤其是 毁灭性的，因为它们发生在年轻的母亲身上。众所周知，乳腺癌的发病率更高， 与其他年轻女性相比，新近分娩的女性的死亡率。然而，人们对此知之甚少 关于乳房以外的其他部位的妊娠相关癌症，如卵巢、结肠/直肠和 皮肤黑色素瘤，相对常见和致命，但很少被检查。有限 有证据表明，卵巢癌、结直肠癌和黑色素瘤的发病率可能较高，而较差。 孕妇或产后妇女的结局比其他年轻妇女的结局要好。潜在的机制可能 涉及胚胎植入所需的促血管生成因子(例如血管内皮生长因子 [血管内皮生长因子])，避免胎儿排斥反应的免疫抑制，以及胎儿生长所需的高水平激素 (例如，胰岛素样生长因子、雌激素和妊娠相关血浆蛋白A[Pappa])。我们 假设由于血管生成、免疫抑制和生长因子的致癌作用， 怀孕和产后期与卵巢、结直肠、 和黑色素瘤癌症。我们将通过进行最大和最全面的 迄今为止基于人群的队列研究的发病率模式、诊断特征和死亡率 使用瑞典整个人口的数据，包括All~3.0，对孕妇和产后妇女的癌症进行研究 1973年至2014年期间，有100万育龄妇女(15至49岁)。瑞典是举办奥运会的理想地点 拟议的研究，因为可以获得几乎100%完整的出生、癌症和死亡登记数据 整个人群，提供了检查妊娠相关癌症所需的大样本量 很好的统计能力。瑞典和美国的癌症发病率和死亡率相似，而且 相同的主要潜在生物机制。我们的具体目标是：(1)确定发病率、诊断率 妊娠相关卵巢的特征、组织学亚型和易感性的时间窗， 以及(2)确定这些与妊娠相关的癌症的死亡率和 他们最常见的亚型。这项拟议的研究具有重大意义和创新性，因为它将是最大的 和迄今为止最全面的研究，以确定发病率、诊断特征和死亡率 与妊娠相关的癌症。它将具有很高的统计能力来确定怀孕是否 与卵巢癌、结直肠癌和黑色素瘤癌症的增加以及这方面的较差预后有关 研究不足的年轻母亲群体，正如我们假设的那样。这一结果将促进我们对 妊娠相关癌症，为临床管理和咨询提供信息，并指导未来对其他 癌症部位和预防或治疗干预措施，以减少妇女的癌症发病率和死亡率。