Understanding Ethnic Differences in Cancer: The Multiethnic Cohort Study

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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.