p21 Expression in Colon Cancer and Modifying Effects of Patient Age and Body Mass Index on Prognosis

p21 (Cyclin-dependent kinase inhibitor-1A, CDKN1A or CIP1) plays a role in regulating cell cycle, and its expression is lost in most colorectal cancers. p21 Is related with energy balance status, cellular senescence, and stem cell aging. Thus, the influence of p21 loss on tumor behavior and clinical...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2009-09, Vol.18 (9), p.2513-2521
Main Authors: OGINO, Shuji, NOSHO, Katsuhiko, FUCHS, Charles S, SHIMA, Kaori, BABA, Yoshifumi, IRAHARA, Natsumi, KIRKNER, Gregory J, HAZRA, Aditi, DE VIVO, Immaculata, GIOVANNUCCI, Edward L, MEYERHARDT, Jeffrey A
Format: Article
Language:English
Subjects:
Age Factors
Aged
Biological and medical sciences
Body Mass Index
CDKN1A
Colonic Neoplasms - genetics
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
colorectal cancer
Cyclin-Dependent Kinase Inhibitor p21 - biosynthesis
Cyclin-Dependent Kinase Inhibitor p21 - deficiency
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Female
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Immunohistochemistry
Male
Medical sciences
Middle Aged
Neoplasm Staging
obesity
Obesity - genetics
Obesity - pathology
outcome
Prognosis
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
survival
Survival Rate
Tumors
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Summary:p21 (Cyclin-dependent kinase inhibitor-1A, CDKN1A or CIP1) plays a role in regulating cell cycle, and its expression is lost in most colorectal cancers. p21 Is related with energy balance status, cellular senescence, and stem cell aging. Thus, the influence of p21 loss on tumor behavior and clinical outcome may be modified by patient age and body mass index (BMI). Using 647 colon cancers in two independent prospective cohorts, p21 loss was observed in 509 (79%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratio (HR) for death, adjusted for potential confounders, including p53, cyclin D1, KRAS, BRAF, PIK3CA , LINE-1 hypomethylation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI). p21 Loss was independently associated with low colon cancer–specific mortality [HR, 0.58; 95% confidence interval (95% CI), 0.38-0.89; adjusted for the covariates including MSI, CIMP, and LINE-1 methylation]. The prognostic effect of p21 loss differed significantly by age at diagnosis ( P interaction < 0.0001) and BMI ( P interaction = 0.002). The adjusted HR for cancer-specific mortality (p21 loss versus p21 expression) was 4.09 (95% CI, 1.13-14.9) among patients
ISSN:1055-9965
1538-7755
DOI:10.1158/1055-9965.EPI-09-0451