DESCRIPTION (provided by applicant): 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
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