Understanding Ethnic Differences in Cancer: The Multiethnic Cohort Study

U 01 CA 164973的全球癌症健康差异补充 “了解癌症的种族差异：多种族队列研究” 主要研究者：Loïc Le Marchand，MD，PhD 标题：了解日裔美国人的高结直肠癌风险：MEC-JPHC比较 摘要： 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 20-032.本补充的目的是更好地了解日裔美国人的高风险， 通过比较两个人群之间的风险因素和癌症相关生物标志物， 显著不同的风险：参加多种族队列（MEC）的日裔美国人和日本人 日本公共卫生中心前瞻性研究（JPHC）队列的参与者。这两个队列 在基因相似的人群中进行，具有非常相似的基于社区的设计， 调查问卷、生物样本采集方案和时间进程。因此，它们提供了一个独特的机会， 为了更好地了解这两个国家癌症发病趋势和风险因素的相似性和差异， 人口。在目标1中，我们建议验证基于血液生物标志物的内脏脂肪组织评分 (VAT)最初在MEC开发，在140名健康的东京中年人中进行增值税测量 available.该评分与MEC中日裔美国人的结直肠癌相关，独立于 BMI和其他危险因素，表明VAT，一种在日本人中大量存在的脂肪， 美国人，可能在解释他们患这种疾病的高风险方面发挥重要作用。相比之下， 在日本很少见。在目标2中，我们建议正式比较结直肠癌的危险因素， MEC（N= 2，092例病例）和JPHC（N= 2，600例病例）之间的日本人。我们将特别关注风险因素 与日裔美国人相关的，如增值税和增值税相关的营养成分，并调查 它们是否解释了两个队列之间结直肠癌发病率的差异。这些风险因素 包括：前瞻性分析：饮食质量（健康饮食指数-2015，日本饮食指数）， 膳食成分（例如，糖，脂肪，膳食纤维，红肉，全熟肉，酒精），身体活动，BMI， 巢式病例对照研究（MEC组381例/对照组381例; JPHC）：VAT生物标志物评分和癌症相关生物标志物（IGF-I、IGFBP 3、胰岛素、HOMA-IR、瘦素， 脂联素、SHBG）。将根据可用的GWAS数据确认遗传祖先的相似性。通过 从外部比较人群中提供非常相似的数据，该补充将进一步促进父母 U 01 CA 164973格兰特的目标是通过关注以下方面来更好地了解癌症中种族/种族差异的原因： 日裔美国人，一个很少被研究的群体。

Global Cancer Health Disparities Supplement to U01 CA164973 “Understanding Ethnic Differences in Cancer: The Multiethnic Cohort Study” Principal Investigator: Loïc Le Marchand, MD, PhD Title: Understanding the high colorectal cancer risk of Japanese Americans: A MEC-JPHC comparison Abstract: This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 20-032. The purpose of this supplement is to better understand the very high risk of Japanese Americans for colorectal cancer by comparing risk factors and cancer-related biomarkers between two populations with substantially different risks: Japanese Americans participating in the Multiethnic Cohort (MEC) and Japanese participants in the Japan Public Health Center-Based Prospective Study (JPHC) Cohort. These two cohorts conducted on genetically similar populations, have very comparable community-based designs, questionnaires, biospecimen collection protocols and time course. Therefore, they provide a unique opportunity to better understand similarities and differences in incidence trends and risk factors for cancer in these two populations. In Aim 1, we propose to validate a blood biomarker-based score for visceral adipose tissue (VAT), originally developed in MEC, among 140 healthy Tokyo middle-aged adults with VAT measurement available. This score was associated with colorectal cancer in Japanese Americans in MEC, independently of BMI and other risk factors, suggesting that VAT, a type of fat disproportionally abundant in Japanese Americans, may play an important role in explaining their high risk for the disease. In contrast, obesity has remained rare in Japan. In Aim 2, we propose to formally compare risk factors for colorectal cancer in Japanese between MEC (N=2,092 cases) and JPHC (N=2,600 cases). We will focus on risk factors particularly relevant to Japanese Americans, such as VAT and VAT-related nutritional components, and investigate whether they explain differences in incidence of colorectal cancer between the two cohorts. These risk factors include: for prospective analyses: diet quality (Healthy Eating Index-2015, Japanese Diet Index), intakes of dietary components (e.g., sugars, fat, dietary fiber, red meat, well-done meat, alcohol), physical activity, BMI, and smoking, and for nested case-control studies (381 cases / 381 controls in MEC; 375 cases / controls in JPHC): the VAT biomarker score and cancer-related biomarkers (IGF-I, IGFBP3, insulin, HOMA-IR, leptin, adiponectin, SHBG). The similarity of genetic ancestry will be confirmed based on available GWAS data. By contributing very similar data from an outside comparison population, this supplement will further the parent U01 CA164973 grant’s aim to better understand reasons for ethnic/racial disparities in cancer by focusing on Japanese Americans, a rarely-studied population.