Etiology of cervical cancer health disparity in American Indian women

美洲印第安女性宫颈癌健康差异的病因学

• 批准号: 8287944
• 负责人: Subhash C. Chauhan
• 金额: $ 32.79万
• 依托单位: SANFORD RESEARCH/USD
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-21 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8287944
• 关键词: Affect; African American; American Indians; Aryl Hydrocarbon Receptor; Benzo(a)pyrene; Binding; Cancer Burden; Cancer Etiology; Carcinogens; Caucasians; Caucasoid Race; Cell Culture Techniques; Cells; Cervical; Cervix Mucus; Cessation of life; Clinical; Communities; Curcumin; Data; Development; Epidemiology; Etiology; Event; Exposure to; Hispanics; Human Papillomavirus; Immune response; Immunoglobulins; Incidence; Infection; Laboratories; Lead; Life; Link; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Methods; Modeling; Molecular; Molecular Profiling; Oncogene Proteins; Oncogenic; Pap smear; Pathology; Pathway interactions; Prevention; Principal Investigator; Repression; Research; Risk Factors; Sampling; Second Primary Cancers; Severities; Signal Transduction; Smoke; Smoking; Testing; Time; Tobacco smoke; Underserved Population; Woman; base; cancer diagnosis; cancer health disparity; cancer therapy; cervical cancer prevention; cofactor; cohort; cytokine; human papilloma virus oncogene; innovation; mortality; mouse model; northern plains; novel; pre-clinical; programs; tumorigenesis

DESCRIPTION (provided by applicant): Cervical cancer is the second most frequently diagnosed cancer and the second leading cause of cancer related deaths in women worldwide. American Indian (AI) women living on the Northern Plains have a greater incidence of cervical cancer and suffer from a higher mortality rate. Our recent studies have shown that AI women have more than twice the incidence of HPV infection and that HPV positive AI women have a two times higher likelihood of having abnormal PAP tests than HPV positive Caucasian women; suggesting underlying causes which increase HPV pathology. One potential cofactor may be smoke exposure and its effects on the host immune response and HPV oncogenesis. Our data indicate that 4 times more AI women smoke as compared to Caucasian women and the majority of HPV positive AI women smoke. While smoking is a recognized risk factor for cervical cancer, the molecular interactions between HPV and smoke compounds are unknown. Our laboratory has recently shown that smoke carcinogen Benzo[a]Pyrene (BaP) increases the expression of HPV oncoproteins, suggesting a direct molecular link between HPV infection and exposure to smoke. We have also identified that curcumin, a natural anti-cancer compound, effectively inhibits the expression of HPV oncoproteins. Based on this compelling evidence, we hypothesize that exposure to tobacco smoke synergizes with HPV infection and increases the incidence and severity of cervical cancer in American Indian women by increasing the expression of HPV oncoproteins (E6/E7) and modulating cellular/humoral immune responses. Additionally, we hypothesize that curcumin or nanocurcumin may be effective methods for the repression of HPV infection in AI women. We propose to 1) investigate novel mechanisms of synergy between HPV infection, BaP and the development of cervical cancer, 2) evaluate the efficacy of curcumin/nanocurcumin to suppress HPV oncogene expression in preclinical and clinical settings, and 3) to investigate the effect of smoke exposure on cervical immune responses. The results of this study will provide information regarding underlying etiological factors that are responsible for cervical cancer health disparity in AI women and will ultimately reduce the burden of cervical cancer. PUBLIC HEALTH RELEVANCE: Project Narrative American Indian (AI) women living in the Northern Plains have a greater incidence of cervical cancer and suffer from a higher mortality rate. This study will provide information regarding etiological factors that are responsible for cervical cancer health disparity in AI women, ultimately reducing the burden of cervical cancer in AI women and serving as a platform to reduce cervical cancer in other underserved populations.

描述（由申请人提供）：宫颈癌是全世界女性中第二次最常见的癌症，也是癌症与癌症相关的第二大原因。居住在北部平原上的美洲印第安人（AI）妇女的宫颈癌发生率更高，死亡率更高。我们最近的研究表明，AI女性的HPV感染发病率是HPV阳性妇女的两倍以上，并且患有异常的PAP测试的可能性是HPV阳性高加索妇女的两倍。提出了增加HPV病理的根本原因。一种潜在的辅助因子可能是烟雾侵害及其对宿主免疫反应和HPV肿瘤发生的影响。我们的数据表明，与高加索妇女和大多数HPV阳性AI女性吸烟相比，AI女性吸烟的4倍。尽管吸烟是宫颈癌的公认危险因素，但HPV和烟雾化合物之间的分子相互作用尚不清楚。我们的实验室最近表明，烟雾致癌[A] pyrene（BAP）增加了HPV癌蛋白的表达，这表明HPV感染与暴露于烟雾之间的直接分子联系。我们还确定，天然抗癌化合物姜黄素有效地抑制了HPV癌蛋白的表达。基于这一令人信服的证据，我们假设暴露于HPV感染与HPV感染协同作用，并通过增加HPV癌蛋白（E6/E7）的表达并调节细胞/性能免疫反应，从而增加了美洲印度女性宫颈癌的发生率和严重性。此外，我们假设姜黄素或纳米苏蛋白可能是抑制AI女性HPV感染的有效方法。我们提出1）研究HPV感染，BAP和宫颈癌发展之间协同作用的新型机制，2）评估姜黄素/纳米毒素在抑制临床前和临床环境中抑制HPV癌基因表达的功效，以及3）研究对宫颈免疫反应的烟雾影响的影响。这项研究的结果将提供有关AI女性宫颈癌健康差异的潜在病因因素的信息，并最终减轻宫颈癌的负担。 公共卫生相关性： 居住在北部平原的美国印第安人（AI）妇女的项目叙事率更大，宫颈癌发生率更高，死亡率更高。这项研究将提供有关导致宫颈癌健康差异的病因学因素的信息 在AI妇女中，最终减轻了AI妇女宫颈癌的负担，并作为减少其他服务不足人群中宫颈癌的平台。