Colorectal cancer disparities:Racial differences in colorectal adenopolyps and altered expression of Mitochondrial genes

结直肠癌差异：结直肠腺息肉的种族差异和线粒体基因表达的改变

• 批准号: 9280274
• 负责人: Felix O Aikhionbare
• 金额: $ 10.65万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9280274
• 关键词: Adenocarcinoma; Adenomatous Polyps; Affect; African American; Age; Age-Years; Alabama; Anatomy; Architecture; Area; Autopsy; Behavior; Biology; Biopsy; Biopsy Specimen; Body mass index; Carcinoma; Caucasians; Clinical; Cluster Analysis; Colorectal; Colorectal Adenocarcinoma; Colorectal Adenoma; Colorectal Cancer; Colorectal Neoplasms; Colorectal Polyp; Coupling; Data; Diagnostic; Disease; Documentation; Dysplasia; Early Diagnosis; Epithelium; Frequencies; Funding; Gene Expression; Gene Mutation; Genes; Genetic Polymorphism; Genome; Genomics; Gland; Goals; Guidelines; Histologic; Histology; Histopathology; Incidence; Individual; Laboratories; Large Intestine Carcinoma; Lesion; Link; Location; Malignant Neoplasms; Microdissection; Mitochondria; Mitochondrial DNA; Molecular Profiling; Morphology; Mutation; Normal tissue morphology; Outcome; Oxidative Stress; PTGS2 gene; Paper; Patients; Pattern; Persons; Play; Polyps; Population; Precancerous Polyp; Predisposition; Premalignant; Prevalence; Proteins; Quantitative Reverse Transcriptase PCR; RNA; Race; Recommendation; Regression Analysis; Research Design; Reverse Transcription; Risk Assessment; Role; Sample Size; Sampling; Source; Statistical Data Interpretation; Subgroup; Sulfhydryl Compounds; Surface; Survival Rate; Testing; Tissue Banks; Tissue Sample; Tissues; Transcript; Tubular formation; Tubulovillous Adenoma; Tumor Biology; Tumor stage; United States National Institutes of Health; Universities; Variant; Villous; Villous Adenoma; Work; adenoma; age difference; age group; age related; aged; base; biomarker identification; cancer health disparity; carcinogenesis; case control; caucasian American; clinically relevant; cohort; early experience; experience; genetic variant; human tissue; innovation; insertion/deletion mutation; insight; mitochondrial DNA mutation; novel; outcome forecast; overexpression; polyposis; predict clinical outcome; public health relevance; racial difference; racial disparity; repaired; screening; treatment strategy; tumor; tumor progression

Abstract: Regardless of race, 50 years of age is the current screening recommendations for colorectal cancer (CRC) disease based on an assumption that the prevailing CRC disparities are relatively due to differences in access to quality screening and the post diagnostic therapies. However, several lines of evidence have suggested that in younger age groups, AA have twice the CRC incidence rate as Whites, and their stage- adjusted CRC survival rates are lower than Whites. Given that most CRCs arise from precancerous of adenomatous polyps (adenopolyps) that evolve into invasive adenocarcinoma, it is plausible that certain “modifying” genes expression may potentially responsible for the observation in AA experience to earlier adenopolyps initiation and more rapid adenopolyps progression to adenocarcinoma. If such is the case, one potential factor in the persistent of CRC disparities may be the race-nonconforming/or neutral age guideline for screening initiation. Studies regarding age-related AA-White differences in CRC progression through the intermediate stages (polyp sizes of tubular, tubulovillous, and villous, and dysplastic histology) are needed. To establish such evidence, it requires genetic alteration study in a modifying gene(s) and a tissue source representing the colorectal adenopolyp prevalence and profile in the population from a large enough autopsy sample size with complete adenopolyps clearance and having complete colorectal adenopolyps documentation. Our study will leverage a unique of 640 colorectal adenopolyp/ cancer cases and 1280 control tissue samples in a frequency matched nested case-control within our lab and Southern Division Co-operative Human tissues Network at University of Alabama collected through previous NIH-funded studies. The sample size has sufficient statistical power to compare AA and Whites on precancerous of colorectal adenopolyps prevalence and cancer-relevant features with difference age strata. These tissue collections are large and well-annotated by micro-dissection. Our laboratory recently demonstrated that there were progressive increase of mitochondrial gene expressions in colorectal adenopolyps and carcinomas when compared to their normal surrounding tissues (accepted paper Tumor Biology #TUBI-16-00926R1), suggesting that certain mt-genes expression are involved in the malignancy of colorectal adenopolyps to invasive adenocarcinoma. Based on these data, the central hypothesis of this project is that over-expression of certain mt-genes play a role in the aggressiveness of precancerous colorectal tumor behavior within younger AA which are reflected in their high incidence and low survival rate of this disease. To test this hypothesis, we will determine the level of mt-genes alterations in colorectal adenopolyps between AA-White subgroups. Also, we will evaluate our results relative to AA-White differences within 10 year age strata and their related features (size, histology, anatomic location, dysplasia status, and adenocarcinoma), as well as body mass index (BMI) using univariate statistical tests, multiple regression and cluster analysis.

摘要：不分种族，50岁是目前结直肠癌的筛查建议。 (CRC)疾病基于一种假设，即普遍存在的CRC差异相对是由于 获得高质量的筛查和诊断后治疗。然而，有几条证据表明 提示在年轻人群中，AA的结直肠癌发病率是白人的两倍，他们的分期- 调整后的CRC存活率低于白人。鉴于大多数癌起源于癌前病变 腺瘤性息肉(腺息肉)演变为侵袭性腺癌，这是可信的， “修饰”基因表达可能是再生障碍性贫血早期观察到的潜在原因。 腺息肉的启动和更快的腺息肉进展为腺癌。如果是这样的话，一个 持续存在结直肠癌差异的潜在因素可能是种族不一致/或中性的年龄指南 启动筛选。关于年龄相关的AA-White在结直肠癌进展中的差异的研究 中期(管状、管状、绒毛和发育不良的组织学息肉大小)是必需的。至 要建立这样的证据，需要研究修饰基因(S)和组织来源的遗传变化 从一个足够大的尸检中代表结直肠腺息肉的患病率和特征 样本大小与完整的腺息肉清除，并拥有完整的结直肠腺息肉文件。 我们的研究将利用640例结直肠腺息肉/癌症病例和1280例对照组织样本 本实验室与南方师合作人体组织中频率匹配的嵌套病例对照研究 阿拉巴马大学通过NIH资助的先前研究收集的网络。样本量为 有足够的统计能力比较AA和White在结直肠腺息肉癌前病变中的患病率 不同年龄层次的肿瘤相关特征。这些组织集很大，注释也很好 通过显微解剖。我们实验室最近证实了线粒体进行性增加。 结直肠腺息肉和癌组织中基因表达与正常组织的比较 组织(接受的论文肿瘤生物学#Tubi-16-00926R1)，表明某些mt-基因的表达是 参与了大肠息肉向侵袭性腺癌的恶变。根据这些数据， 该项目的中心假设是某些mt基因的过度表达在肿瘤的侵袭性中发挥了作用。 青年再障患者的癌前病变行为表现为高发病率和低发病率 这种疾病的存活率。为了验证这一假设，我们将确定mt-基因在 AA-White亚组之间的结直肠腺息肉。此外，我们还将评估我们相对于AA-White的结果 10年内地层差异及其相关特征(大小、组织学、解剖位置、发育不良 状态和腺癌)，以及使用单变量统计检验的身体质量指数(BMI)，多个 回归分析和聚类分析。