Obesity is estimated to explain 15-20% of all cancer deaths in the U.S. Our current understanding of the mechanisms involved is only partial, especially for the two most common obesity-related cancers (breast and colorectal), and has not led to effective interventions. As the current obesity epidemic continues unabated, particularly among the poor and lower middle class, it is feared that the recent progress in lowering cancer rates and in improving the nation's health may be reversed, and health disparities worsened. Evidence suggests that the main U.S. ethnic/racial populations not only have different mean levels of body mass index (BMI) but also varying patterns of fat distribution. Compared to whites, African Americans experience a higher prevalence of obesity, with greater amounts of superficial abdominal subcutaneous fat which carries a lower metabolic risk than visceral fat or deep subcutaneous fat. In contrast, Asians have lower total adiposity but more visceral fat and experience higher rates of metabolic diseases. Hispanics have more overall and visceral adiposity and Native Hawaiians have high obesity rates; both groups are also at high risk for metabolic diseases. This heterogeneity in BMI levels and types of obesity existing among these 5 ethnic groups represented in the Multiethnic Cohort (MEC) offers a unique setting to study obesity and cancer.

Similarly, the marked differences observed in the incidence of obesity-related cancers among the five ethnic/racial groups in the MEC reflect those described by SEER in their source populations. In addition, we observed striking ethnic/racial differences in the BMI-cancer association. For example, for breast cancer, the association was strongest for Native Hawaiians and Japanese Americans and occurred starting at low levels of excess BMI (>25 kg/m2). In contrast, the association in the other groups occurred only at high BMI levels (>30 kg/m2), if at all. A similar pattern was seen for colorectal cancer and diabetes. We interpret these differences as supporting an important role for body fat distribution, in addition to amount, in determining cancer risk. This has been suggested by a number of studies that assessed central obesity with waist and hip measurements. However, there is a critical need for a more comprehensive study of body fat distribution patterns (assessed by reference imaging methods) in U.S. ethnic/racial minorities and their association with cancer risks. We have initiated a large study within the MEC that will: 1) describe amount and distribution of body fat among older adults of five major U.S. ethnic/racial populations using whole body DXA and abdominal MRI; 2) identify nutritional, behavioral, biochemical, hormonal, genetic, metabolomic and gut microbiome determinants of these fat distribution patterns; 3) investigate inter-relationships among these factors to better understand the causes of obesity; 4) build integrated predictive signatures for these body fat compartments; and 5) test prospectively these predictive signatures for associations with breast and colorectal cancer risks in the MEC.

Citation Format: Loic Le Marchand. Obesity, body fat distribution, and cancer risk in the Multiethnic Cohort Study. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA44.