Obesity, Body Fat Distribution, and Cancer Risk in the Multiethnic Cohort

描述（由申请人提供）：肥胖解释了美国大约20%的癌症。我们目前对相关机制的理解只是部分的，还没有导致有效的干预措施。由于目前的肥胖流行病有增无减，特别是在穷人和中下层阶级中，人们担心最近在降低癌症发病率方面取得的进展可能会逆转，健康差距可能会恶化。在多民族队列（MEC）研究中，五个民族/种族人群（非裔美国人、日裔美国人、拉丁美洲人、夏威夷原住民、白人）的肥胖模式明显不同。最令人惊讶的是，我们观察到BMI与癌症之间存在显著的种族差异。例如，对于乳腺癌，这种关联是最强的，并且从低BMI水平（bbb25 kg/m2）开始发生，对于日裔美国人和夏威夷原住民来说，这两个群体的中心肥胖更严重。相比之下，其他族群的关联仅发生在高BMI水平（bbb30 kg/m2）。我们将这些差异解释为身体脂肪分布的重要作用，而不是数量。我们的初步数据还表明，通过DXA和MRI评估，除了BMI和腰围测量外，考虑生活方式变量和生物标志物可以改善对中心性肥胖、腹内内脏脂肪和肝脏脂肪的大小预测。到目前为止，还没有关于美国少数民族肥胖模式及其决定因素及其与癌症风险关系的全面研究。我们提出了一个新的研究项目，将：1)使用全身DXA和腹部MRI描述美国5个主要民族/种族人群的体脂量和分布；2)确定这些脂肪分布模式的营养、行为、生化、遗传、代谢组学和肠道微生物组预测因子；3)调查这些预测因素之间的相互关系，以更好地了解肥胖的原因；4)建立这些体脂分布表型的综合预测模型；5)前瞻性地测试这些预测表型与MEC中乳腺癌和结直肠癌风险的关联。更好地了解少数民族/种族肥胖的原因可能为预防和治疗开辟新的途径，并有助于缩小健康差距。

DESCRIPTION (provided by applicant): 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.