Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 27, Issue 27, Pages 4591-4598Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2009.22.8858
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Funding
- National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, K07 CA97992]
- Bennett Family Fund
- Entertainment Industry Foundation National Colorectal Cancer Research Alliance
- Japan Society for Promotion of Science
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Purpose Loss of heterozygosity (LOH) at chromosome 18q frequently occurs late during colon cancer development and is inversely associated with microsatellite instability (MSI). 18q LOH has been reported to predict shorter survival in patients with colorectal cancer, whereas MSI-high status has been associated with superior prognosis. However, it is unclear whether 18q LOH in colorectal cancer has any prognostic implication independent of MSI status and other potential predictors of clinical outcome. Patients and Methods Among 555 non-MSI-high colorectal cancers (stage I to IV) in two independent prospective cohort studies, we examined 18q LOH in relation to other molecular events and patient survival. Cox proportional hazard models computed hazard ratio of death, adjusted for clinical and tumoral characteristics, including KRAS, BRAF, PIK3CA, beta-catenin, p53, CpG island methylator phenotype, LINE-1 methylation, and John Cunningham (JC) virus T antigen. Results In multivariate logistic regression, 18q LOH was independently associated with JC virus T antigen (odds ratio [OR] = 1.93; P = .0077), body mass index >= 30 kg/m(2) (obesity; OR = 2.01; P = .014), high tumor grade (OR = 0.40; P = .018), KRAS mutation (OR = 0.66; P = .40), and LINE-1 hypomethylation (for a 30% decrease; OR = 1.92; P = .045). Five-year colorectal cancer-specific survival was 75% among patients with 18q LOH-positive tumors and 74% among those with 18q LOH-negative tumors (log-rank P = .80). Five-year overall survival was 70% among patients with 18q LOH-positive tumors and 68% among those with 18q LOH-negative tumors (log-rank P = .54). Multivariate analysis did not show prognostic significance of 18q LOH. Conclusion In our large prospective study of patients with non-MSI-high colorectal cancer, 18q LOH or allelic imbalance was not associated with patient survival. J Clin Oncol 27:4591-4598. (C) 2009 by American Society of Clinical Oncology
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