Epidemiologic and scientific research shows that obesity has a significant influence on the risk of developing colorectal cancer. However, associations between adiposity and colorectal cancer (CRC) prognosis are less convincing. While some studies have found severely obese patients (BMI, e35 kg/m2) to have an increased risk of recurrence and/or death, most studies have found no association between body mass index (BMI) or weight gain after diagnosis and CRC prognosis. The lack of consistent findings between BMI and colorectal cancer endpoints may be due in part to the fact that BMI may be a poor surrogate for body composition in the context of illness. Adipose tissue and muscle mass exert powerful but different endocrine, immune, and hormonal influences within the body. Though overweight persons tend to have both higher amounts of lean and fat mass, low levels of muscle mass may be present in overweight or obese people;sarcopenia (muscle wasting) is common among cancer survivors, even in the presence of fat gain. Therefore, we propose to use abdominal CT scans collected as part of routine staging and surveillance both at diagnosis and 1-2 years after diagnosis, to assess fat and muscle mass and to examine the relationship of body composition to CRC survival in a cohort of persons (n=3546) diagnosed between 2005 and 2010 with Stage I-III invasive colorectal cancer (CRC) at Kaiser Permanente Northern California (KPNC). Specifically, we will examine the level of muscle wasting (sarcopenia) and excess fat mass (FM) in CRC survivors at diagnosis (Aim 1), the association between FM and muscle mass at diagnosis and CRC survival (Aim 2), whether changes in FM and muscle mass measured between diagnosis and 1 to 2 years after diagnosis vary by weight change post-diagnosis (Aim 3), and whether changes in FM and muscle mass measured between diagnosis and 1 to 2 years after diagnosis are associated with CRC survival (Aim 4). This study uses a novel, state-of-the art tool to collect more accurate measures of body composition than standard measures of height and weight, and could provide important insight into the role of energy balance and body composition in cancer survival. This study will enable identification of CRC patients who are at high risk for muscle wasting and may improve our understanding of why BMI is related to incident CRC but not CRC outcomes. The use of CT scans to assess fat/muscle mass could easily be done in the clinical or epidemiologic setting, adding an important physiologic measure to BMI to help target and personalize weight control strategies and other treatments to prevent muscle mass loss, potentially improving survival. Findings from this study may thus lead to altered clinical practice. Additionally, insights regarding the role of fat/muscle mass in CRC prognosis may provide new avenues for future research about the role of energy balance in cancer survival

Public Health Relevance

Obesity is related to colorectal cancer (CRC) incidence but not CRC prognosis and this and may be due to the fact that in the context of illness, BMI is a poor surrogate for body composition. This study will examine the extent of excess body fat and muscle loss among persons diagnosed with colorectal cancer in order to see if levels of body fat or muscle mass are related to survival. Study findings could provide important insight into the role of energy balance and body composition in cancer survival and may lead to more tailored treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA175011-02
Application #
8661714
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Elena, Joanne W
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$596,795
Indirect Cost
$177,629
Name
Kaiser Foundation Research Institute
Department
Type
DUNS #
150829349
City
Oakland
State
CA
Country
United States
Zip Code
94612
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Cespedes Feliciano, Elizabeth M; Lee, Valerie S; Prado, Carla M et al. (2017) Muscle mass at the time of diagnosis of nonmetastatic colon cancer and early discontinuation of chemotherapy, delays, and dose reductions on adjuvant FOLFOX: The C-SCANS study. Cancer 123:4868-4877
Caan, Bette J; Meyerhardt, Jeffrey A; Kroenke, Candyce H et al. (2017) Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study). Cancer Epidemiol Biomarkers Prev 26:1008-1015
Meyerhardt, Jeffrey A; Kroenke, Candyce H; Prado, Carla M et al. (2017) Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population. Cancer Epidemiol Biomarkers Prev 26:30-37
Caan, Bette J; Meyerhardt, Jeffrey A; Prado, Carla M (2017) Explaining the Obesity Paradox-Response. Cancer Epidemiol Biomarkers Prev 26:1576
Cespedes Feliciano, Elizabeth M; Prentice, Ross L; Aragaki, Aaron K et al. (2017) Methodological considerations for disentangling a risk factor's influence on disease incidence versus postdiagnosis survival: The example of obesity and breast and colorectal cancer mortality in the Women's Health Initiative. Int J Cancer 141:2281-2290
Cespedes Feliciano, Elizabeth M; Kroenke, Candyce H; Meyerhardt, Jeffrey A et al. (2016) Metabolic Dysfunction, Obesity, and Survival Among Patients With Early-Stage Colorectal Cancer. J Clin Oncol :
Kroenke, Candyce H; Neugebauer, Romain; Meyerhardt, Jeffrey et al. (2016) Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams. JAMA Oncol 2:1137-45