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Mutations in BRAF correlate with poor survival of colorectal cancers in Chinese population

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Abstract

Purpose

Mutations in KRAS and BRAF genes were associated with treatment failure from EGF receptor inhibitors in colorectal cancer (CRC) patients. However, whether these mutations were associated with survival in patients not treated with EGF receptor inhibitors remained controversial. Moreover, few data were available in Chinese. Therefore, we aimed to evaluate the impact of KRAS and BRAF mutations on the survival of Chinese CRC patients.

Methods

CRC patients who underwent surgery between October 2003 and April 2006 were included in this study. They were observed until June 30, 2010 or when death was ascertained by the National Death Registration System. Prospectively collected fresh frozen tumor tissues were used for detection of mutations at codons 12, 13, and 61 of the KRAS gene and exons 11 and 15 of BRAF gene by PCR amplification followed by direct sequencing.

Results

Among the 314 patients, KRAS and BRAF mutations were detected in 65 (20.7%) and 12 (3.8%) patients, respectively. KRAS mutations appeared to occur more frequently in females than males (p = 0.039) and in non-smokers (p = 0.039). KRAS and BRAF mutations were significantly associated with the proximal location of cancer (p = 0.017 and 0.001, respectively). In the univariate analysis, KRAS and BRAF mutations were not associated with survival. However, BRAF mutations were associated with a significantly worse overall survival (hazard ratio = 3.91, 95% confidence interval 1.31 to 11.66, p = 0.014) in the multivariate Cox proportional hazard model after adjustment for all direct clincopathological variables.

Conclusion

BRAF mutations, but not KRAS mutations, were associated with a worse outcome in Chinese CRC patients.

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Acknowledgment

As for financial support, Jyh-Ming Liou received research grants from the National Taiwan University, College of Medicine (grant number: NTU-99R3110002). Jyh-Ming Liou and Ming-Shiang Wu contributed equally to this work. All the authors do not have conflict of interest to be declared in this work. We would like to express our special thanks to the staff of the Eighth Core Lab, Department of Medical Research, National Taiwan University Hospital for the technical support during the study.

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Jyh-Ming Liou, Ming-Shiang Wu, Han-Mo Chiu, Mei-Jyh Chen, Chien-Chuan Chen, Hsiu-Po Wang & Jaw-Town Lin

  2. Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan

    Jyh-Ming Liou

  3. Department of Primary Care Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Ming-Shiang Wu

  4. Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Chia-Tung Shun

  5. Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan

    Jaw-Town Lin

  6. Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Road, Taipei, Taiwan

    Jin-Tung Liang

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  1. Jyh-Ming Liou
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Correspondence to Jin-Tung Liang.

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Liou, JM., Wu, MS., Shun, CT. et al. Mutations in BRAF correlate with poor survival of colorectal cancers in Chinese population. Int J Colorectal Dis 26, 1387–1395 (2011). https://doi.org/10.1007/s00384-011-1229-1

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