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）：宫颈癌是全球第二大最常见的癌症，也是女性癌症相关死亡的第二大原因。生活在北方平原的美洲印第安妇女宫颈癌发病率较高，死亡率也较高。我们最近的研究表明，AI女性的HPV感染发生率是HPV感染的两倍多，HPV阳性的AI女性的PAP检测异常的可能性比HPV阳性的白人女性高两倍;这表明了增加HPV病理的潜在原因。一个潜在的辅因子可能是烟雾暴露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，与白人女性相比，AI女性吸烟的人数是白人女性的4倍，大多数HPV阳性的AI女性吸烟。虽然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，烟雾致癌物苯并[a]芘（BaP）增加HPV癌蛋白的表达，表明HPV感染和暴露于烟雾之间存在直接的分子联系。我们还发现，姜黄素，一种天然的抗癌化合物，有效地抑制HPV癌蛋白的表达。基于这一令人信服的证据，我们假设，暴露于烟草烟雾协同HPV感染，并通过增加HPV癌蛋白（E6/E7）的表达和调节细胞/体液免疫反应，增加美国印第安妇女宫颈癌的发病率和严重程度。此外，我们假设姜黄素或纳米姜黄素可能是抑制AI女性HPV感染的有效方法。我们建议1）研究HPV感染，BaP和宫颈癌发展之间协同作用的新机制，2）评估姜黄素/纳米姜黄素在临床前和临床环境中抑制HPV癌基因表达的功效，以及3）研究烟雾暴露对宫颈免疫反应的影响。这项研究的结果将提供有关导致AI女性宫颈癌健康差异的潜在病因因素的信息，并最终减少宫颈癌的负担。 公共卫生关系： 生活在北方平原的美洲印第安妇女宫颈癌发病率较高，死亡率也较高。这项研究将提供有关宫颈癌健康差异的病因学因素的信息 在人工智能妇女中，最终减轻人工智能妇女的宫颈癌负担，并作为减少其他服务不足人群宫颈癌的平台。