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Article first published online: 19 NOV 2011
Copyright © 2011 UICC
International Journal of Cancer
Volume 131, Issue 5, pages 1169–1178, 1 September 2012
How to Cite
Morikawa, T., Kuchiba, A., Liao, X., Imamura, Y., Yamauchi, M., Qian, Z. R., Nishihara, R., Sato, K., Meyerhardt, J. A., Fuchs, C. S. and Ogino, S. (2012), Tumor TP53 expression status, body mass index and prognosis in colorectal cancer. Int. J. Cancer, 131: 1169–1178. doi: 10.1002/ijc.26495
This article was published online November 19, 2011. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected December 1, 2011.
T.M., A.K. and X.L. contributed equally to this work.
- Issue published online: 27 JUN 2012
- Article first published online: 19 NOV 2011
- Accepted manuscript online: 31 OCT 2011 04:30AM EST
- Manuscript Accepted: 7 OCT 2011
- Manuscript Revised: 20 SEP 2011
- Manuscript Received: 5 AUG 2011
- National Institute of Health (NIH). Grant Numbers: P01 CA87969, P01 CA55075, P50 CA127003, R01 CA151993
- Bennett Family Fund
- Entertainment Industry Foundation through National Colorectal Cancer Research Alliance, Japan Society for Promotion of Science
- colon cancer;
- molecular pathological epidemiology;
- tumor suppressor;
Inactivation of the TP53 (p53) pathway by TP53 mutations is one of key steps in colorectal carcinogenesis. TP53 also plays an important role in cellular energy metabolism. We hypothesized that TP53-altered tumor cells might behave aggressively independent of energy balance, while progression of TP53-intact cells might depend on excess energy balance. Utilizing a database of 1,060 colon and rectal cancer patients in two prospective cohort studies, we evaluated TP53 expression by immunohistochemistry. Among 1,060 colorectal cancers, 457 (43%) tumors were positive for TP53. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, the CpG island methylator phenotype, LINE-1 methylation, KRAS, BRAF and PIK3CA. TP53 positivity was not significantly associated with cancer-specific survival in univariate analysis with HR of 1.16 [95% confidence interval (CI) = 0.92–1.45], which became significant after stage adjustment (multivariate HR = 1.30; 95% CI = 1.02–1.65). Notably, we found a possible modifying effect of patient's body mass index (BMI) on tumor TP53. In non-obese patients (BMI < 30 kg/m2), TP53 positivity was associated with shorter cancer-specific survival (multivariate HR = 1.53; 95% CI = 1.17-2.00), while TP53 positivity was not significantly associated with survival among obese patients (BMI ≥30 kg/m2). Effect of TP53 positivity on cancer-specific survival significantly differed by BMI (pinteraction = 0.0051). The adverse effect of obesity on patient mortality was limited to TP53-negative patients. These molecular pathological epidemiology data may support a dual role of TP53 alterations in cell-cycle deregulation and cell autonomy with respect to energy balance status.