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Observational Study
. 2015 Jan 28;21(4):1275-83.
doi: 10.3748/wjg.v21.i4.1275.

Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

Shigenori Kadowaki  1 , Miho Kakuta  1 , Shuhei Takahashi  1 , Akemi Takahashi  1 , Yoshiko Arai  1 , Yoji Nishimura  1 , Toshimasa Yatsuoka  1 , Akira Ooki  1 , Kensei Yamaguchi  1 , Keitaro Matsuo  1 , Kei Muro  1 , Kiwamu Akagi  1
Affiliations
Observational Study

Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

Shigenori Kadowaki et al. World J Gastroenterol. .

Abstract

Aim: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability (MSI) status in Japanese colorectal cancer (CRC) population.

Methods: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage I-III CRC and examined associations of these mutations with disease-free survival (DFS) and overall survival (OS) using uni- and multivariate Cox proportional hazards models.

Results: KRAS and BRAF mutations were detected in 312 (38%) of 812 and 40 (5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males (P=0.02), while the presence of BRAF mutations was significantly associated with the female gender (P=0.006), proximal tumor location (P<0.001), mucinous or poorly differentiated histology (P<0.001), and MSI-high tumors (P<0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS (HR=1.35; 95%CI: 1.03-1.75) and OS (HR=1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS (HR=2.20; 95%CI: 1.19-4.06) and OS (HR=2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.

Conclusion: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected CRC.

Keywords: BRAF; Colorectal cancer; KRAS; Microsatellite instability; Prognostic factor.

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Figures

Figure 1
Figure 1
Kaplan-Meier curves for disease-free survival and overall survival according to KRAS or BRAF status. A: Disease-free survival (DFS) according to KRAS status; B: Overall survival (OS) according to KRAS status; C: DFS according to BRAF status; D: OS according to BRAF status.
Figure 2
Figure 2
Stratified analysis of KRAS or BRAF status and overall survival. Loge [adjusted hazard ratio (HR)] and 95%CI for BRAF and KRAS mutant tumors (vs wild-type tumors) in various strata are shown. A: KRAS mutant tumors; B: BRAF mutant tumors.
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References

    1. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–2460. - PMC - PubMed
    1. Wang L, Cunningham JM, Winters JL, Guenther JC, French AJ, Boardman LA, Burgart LJ, McDonnell SK, Schaid DJ, Thibodeau SN. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003;63:5209–5212. - PubMed
    1. Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–793. - PubMed
    1. Yagi K, Akagi K, Hayashi H, Nagae G, Tsuji S, Isagawa T, Midorikawa Y, Nishimura Y, Sakamoto H, Seto Y, et al. Three DNA methylation epigenotypes in human colorectal cancer. Clin Cancer Res. 2010;16:21–33. - PubMed
    1. Watanabe T, Yoshino T, Uetake H, Yamazaki K, Ishiguro M, Kurokawa T, Saijo N, Ohashi Y, Sugihara K. KRAS mutational status in Japanese patients with colorectal cancer: results from a nationwide, multicenter, cross-sectional study. Jpn J Clin Oncol. 2013;43:706–712. - PubMed

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