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 癌症是生殖年龄女性死亡的第二大原因。与妊娠相关的癌症 （在怀孕期间或产后5年期间诊断）正在增加，高度致命，尤其是 毁灭性的是因为它们发生在年轻母亲中。众所周知，乳腺癌的发病率更高和 与其他年轻女性相比，最近出生的妇女的死亡率。但是，鲜为人知 大约在乳房以外的其他部位的妊娠相关癌症，例如卵巢，结肠/直肠和 皮肤的黑色素瘤相对常见和致命，但很少检查。有限的 有证据表明卵巢癌，结直肠癌和黑色素瘤癌症的发生率可能更高且较差 与其他年轻女性相比，怀孕或产后妇女的结果。基本机制可能 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 [VEGF]），免疫抑制以避免胎儿排斥和胎儿生长所需的高水平激素 （例如，胰岛素样生长[IGF]因子，雌激素和与妊娠相关的血浆蛋白A [PAPPA]）。我们 假设由于血管生成，免疫抑制和生长因子的促癌作用， 怀孕和产后时期与卵巢，结直肠癌的发病率和死亡率更高有关 和黑色素瘤癌。我们将通过进行最大，最全面的最大，最全面的方式检验这些假设 基于人群的队列研究迄今为止的发生率模式，诊断特征和死亡率 孕妇和产后妇女的癌症使用瑞典整个人口的数据，包括所有〜3.0 1973 - 2014年期间，有百万孕妇（15至49岁）的妇女。瑞典是理想的环境 拟议的研究是因为有近100％的完整出生，癌症和死亡注册表数据可用于 整个人群，提供了检查与妊娠相关的癌症所需的大型样本量 良好的统计能力。瑞典和美国的癌症发病率和死亡率相似，并且具有 相同的主要基础生物学机制。我们的具体目的是：（1）确定发病率，诊断 特征，组织学亚型和与妊娠相关的卵巢敏感性的时间窗口， 结直肠癌和黑色素瘤癌症； （2）确定这些妊娠相关癌症的死亡率和 它们最常见的亚型。拟议的研究具有重要意义和创新性，因为它将是最大的 以及迄今为止的大多数全面研究，以确定的发生率，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是 与卵巢，结直肠癌和黑色素瘤癌症的增加以及在此相关的结果较差 正如我们假设的那样，年轻母亲的人口正在研究。结果将提高我们对 与妊娠相关的癌症，为临床管理和咨询提供信息，并指导其他其他研究 癌症部位以及预防或治疗性干预措施，以降低女性的癌症发病率和死亡率。