Angiotensin-converting enzyme gene polymorphism (ACEGP) and cancer cachexia (CC): Is there a link?

Abstract

9011 Background: ACEGP greatly influences functional status and is currently the gene most involved in human fitness. The insertion allele (II) (a 287 bp fragment) rather than the deletion allele (DD) for the angiotensin-converting enzyme (ACE) gene is associated with low ACE levels in tissues and enhanced metabolic efficiency, as demonstrated by an improved response to vigorous training in healthy individuals. In addition, lower tissue ACE activity in mice was associated with decreased insulin resistance, greater glucose uptake in the skeletal muscle, and higher glycogen and fat stores. The aim of the study was to gather preliminary data on the potential association between muscle mass and ACEGP in advanced cancer patients (ACP). Methods: Buffy coat serum and plasma was obtained from 55 patients 18 years or older, newly diagnosed with Stage III (inoperable)-IV non-small cell lung cancer and unresectable/ metastatic gastrointestinal cancers seen within the McGill University Health Center. Muscle surface area (MSA-cm2) was calculated from computerized tomography slices at the L3 vertebrae using TOMOVISION SliceOmatic software version 4.3. Muscularity (M-cm2/m2) and lean body mass (LBM-kg) were calculated by extrapolation of image analysis used to quantify lean tissue. Results: ANOVA confirmed significant difference (p<0.001) among MSA (II: 134.04±35.23; ID: 122.37±29.74; DD: 115.22±27.55), M (47.72±8.67; 41.65±9.26; 41.80±9.26), and LBM (43.00±11.21; 39.29±9.46; 37.01±8.77). In a multiple linear regression model, the II allele was associated with higher M (p=0.042) and a trend for higher MSA and LBM (p=0.059) independent of age, gender, diagnosis, and treatment received. Conclusions: Our data suggest ACEGP influences muscle mass in ACP. Further investigations in a larger sample of ACP are underway to determine whether ACEGP is an important predisposing factor to CC-associated muscle wasting. No significant financial relationships to disclose.