Cohort Study of Fatty Acid Synthase Expression and Patient Survival in Colon Cancer
Open Access
- 10 December 2008
- journal article
- gastrointestinal cancer
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 26 (35), 5713-5720
- https://doi.org/10.1200/jco.2008.18.2675
Abstract
Energy balance seems to be important in the pathogenesis of colon cancer. Fatty acid synthase (FASN) is physiologically regulated by energy balance and is often upregulated in colorectal cancer. Nonetheless, the influence of FASN expression on patient outcome is uncertain. Using the database of 647 patients with colon cancer in two independent cohort studies, FASN overexpression was detected in 84 tumors (13%) by immunohistochemistry. Cox proportional hazards models calculated hazard ratios (HRs) of colon cancer–specific and overall mortalities, adjusted for patient characteristics and related tumoral features, including KRAS, BRAF, p53, microsatellite instability and the CpG island methylation phenotype. There were 279 deaths, including 160 colon cancer–specific deaths. FASN overexpression was associated with a significant reduction in colon cancer–specific mortality by both univariate and multivariate analyses (adjusted HR, 0.41; 95% CI, 0.19 to 0.89) and an insignificant trend toward improved overall mortality (adjusted HR, 0.75; 95% CI, 0.50 to 1.13). Notably, the effect of FASN expression on mortality might be different according to body mass index (BMI; Pinteraction = .019); the adjusted HR of overall mortality for FASN overexpression was 0.63 (95% CI, 0.39 to 1.02) among patients with BMI less than 27.5 kg/m2 and 2.91 (95% CI, 1.19 to 7.12) among those with BMI ≥ 27.5 kg/m2. Moreover, the adverse effect of moderate overweight/obesity on overall survival was limited to FASN-positive tumors (adjusted HR, 4.10; 95% CI, 1.14 to 14.8; BMI ≥ 27.5 kg/m2 v < 27.5 kg/m2). Among nonobese patients with colon cancer, tumoral FASN overexpression is associated with improved survival, whereas among moderately overweight or obese patients (BMI ≥ 27.5 kg/m2), FASN overexpression may predict a worse outcome.Keywords
This publication has 50 references indexed in Scilit:
- Fatty Acid Synthase Gene Is Up-regulated by Hypoxia via Activation of Akt and Sterol Regulatory Element Binding Protein-1Cancer Research, 2008
- CpG Island Methylator Phenotype-Low (CIMP-Low) in Colorectal Cancer: Possible Associations with Male Sex and KRAS MutationsThe Journal of Molecular Diagnostics, 2006
- Body Mass Index and Outcomes in Patients Who Receive Adjuvant Chemotherapy for Colon CancerJNCI Journal of the National Cancer Institute, 2006
- Physical Activity and Survival After Colorectal Cancer DiagnosisJournal of Clinical Oncology, 2006
- CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancerNature Genetics, 2006
- AMPK and cell proliferation – AMPK as a therapeutic target for atherosclerosis and cancerThe Journal of Physiology, 2006
- Fatty Acid Synthase and Cancer: New Application of an Old PathwayCancer Research, 2006
- Combined Analysis of COX-2 and p53 Expressions Reveals Synergistic Inverse Correlations with Microsatellite Instability and CpG Island Methylator Phenotype in Colorectal CancerNeoplasia, 2006
- Precision and Performance Characteristics of Bisulfite Conversion and Real-Time PCR (MethyLight) for Quantitative DNA Methylation AnalysisThe Journal of Molecular Diagnostics, 2006
- Obesity and colorectal cancer: epidemiology, mechanisms and candidate genesThe Journal of Nutritional Biochemistry, 2006