Obesity explains approximately 20% of all cancers in the U.S. Our current understanding of the mechanisms involved is only partial, and has not led to effective interventions. As the current obesity epidemic continues unabated, especially among the poor and lower middle class, it is feared that recent progress in lowering cancer rates may be reversed, and health disparities worsened. Markedly different patterns of adiposity exist among the five ethnic/racial populations of the Multiethnic Cohort (MEC) Study (African Americans, Japanese Americans, Latinos, Native Hawaiians, whites). Most surprisingly, we observed striking ethnic differences in the association of BMI with cancer. For example, for breast cancer, the association was strongest, and occurred starting at low levels of BMI (>25 kg/m2), for Japanese Americans and Native Hawaiians, two groups with more central adiposity. In contrast, the association in the other ethnic groups occurred only at high BMI levels (>30 kg/m2). We interpret these differences as supporting an important role for body fat distribution, i addition to amount. Our preliminary data also suggest that considering lifestyle variables and biomarkers in addition to BMI and waist measures improves the size predictions for central adiposity, intra-abdominal visceral fat, and liver fat, as assessed by DXA and MRI. Thus far, there has been no comprehensive study of obesity patterns and their determinants in U.S. ethnic/racial minorities and of their relationships with cancer risk. We propose a new program of research that will: 1) describe the amount and distribution of body fat in 5 major U.S. ethnic/racial populations using whole body DXA and abdominal MRI;2) identify nutritional, behavioral, biochemical, genetic, metabolomic and gut microbiome predictors of these fat distribution patterns;3) investigate inter-relationships among these predictors to better understand the causes of obesity;4) build integrated predictive models for these body fat distributions phenotypes;and 5) test prospectively these predicted phenotypes for associations with breast and colorectal cancer risks in the MEC. A better understanding of the causes of obesity in ethnic/racial minorities may open new avenues for prevention and treatment and help in reducing health disparities.

Public Health Relevance

Excess body fat, especially in the abdomen, is hypothesized to contribute to cancer risk. Past studies relied on imperfect measures of fatness (weight for height, waist circumference) and did not often study risk differences among ethnic/racial groups. We propose to measure body fat directly using imaging methods (DXA and MRI) and identify blood biomarkers and lifestyle behaviors that predict body fat distribution in a multiethnic population, n order to test their associations with risks of breast and colorectal cancers in a prospective multiethnic study.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA168530-02
Application #
8538905
Study Section
Special Emphasis Panel (ZCA1-RPRB-B (M1))
Program Officer
Mahabir, Somdat
Project Start
2012-09-01
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$4,422,488
Indirect Cost
$469,547
Name
University of Hawaii
Department
Type
Organized Research Units
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Lim, Unhee; Monroe, Kristine R; Buchthal, Steve et al. (2018) Propensity for Intra-abdominal and Hepatic Adiposity Varies Among Ethnic Groups. Gastroenterology :
Gathungu, Rose M; Larrea, Pablo; Sniatynski, Matthew J et al. (2018) Optimization of Electrospray Ionization Source Parameters for Lipidomics To Reduce Misannotation of In-Source Fragments as Precursor Ions. Anal Chem 90:13523-13532
Gathungu, Rose M; Kautz, Roger; Kristal, Bruce S et al. (2018) The integration of LC-MS and NMR for the analysis of low molecular weight trace analytes in complex matrices. Mass Spectrom Rev :
Citronberg, Jessica S; Wilkens, Lynne R; Le Marchand, Loic et al. (2018) Plasma lipopolysaccharide-binding protein and colorectal cancer risk: a nested case-control study in the Multiethnic Cohort. Cancer Causes Control 29:115-123
Randolph, Timothy W; Zhao, Sen; Copeland, Wade et al. (2018) KERNEL-PENALIZED REGRESSION FOR ANALYSIS OF MICROBIOME DATA. Ann Appl Stat 12:540-566
Maskarinec, Gertraud; Lim, Unhee; Jacobs, Simone et al. (2017) Diet Quality in Midadulthood Predicts Visceral Adiposity and Liver Fatness in Older Ages: The Multiethnic Cohort Study. Obesity (Silver Spring) 25:1442-1450
Fu, Benjamin C; Randolph, Timothy W; Lim, Unhee et al. (2016) Characterization of the gut microbiome in epidemiologic studies: the multiethnic cohort experience. Ann Epidemiol 26:373-9
Utzschneider, Kristina M; Kratz, Mario; Damman, Chris J et al. (2016) Mechanisms Linking the Gut Microbiome and Glucose Metabolism. J Clin Endocrinol Metab 101:1445-54
Gathungu, Rose M; Stavrovskaya, Irina G; Larrea, Pablo et al. (2016) Simple LC-MS Method for Differentiation of Isobaric Phosphatidylserines and Phosphatidylcholines with Deuterated Mobile Phase Additives. Anal Chem 88:9103-10
Citronberg, Jessica S; Wilkens, Lynne R; Lim, Unhee et al. (2016) Reliability of plasma lipopolysaccharide-binding protein (LBP) from repeated measures in healthy adults. Cancer Causes Control 27:1163-6

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