title: Prognostic significance of C-reactive protein polymorphism and KRAS/BRAF in synchronous liver metastasis from colorectal cancer.
abstract: BACKGROUND
  The liver is the most common target organ in the metastasis of colorectal cancer (CRC). Synchronous liver metastases may confer a poorer prognosis than metachronous metastases, and genetic alterations and an inflammatory response have also been associated with a poor prognosis in cases of a liver metastasis arising from CRC. However, few studies have examined the relationship between KRAS mutations and inflammatory status in CRC, especially with respect to liver metastases.
  
  
  METHODS
  The effect of the activated mitogen-activated protein kinase pathway and another protein involved in inflammation, C-reactive protein, in liver metastases were examined. We aimed to determine the impact of the CRP-specific single nucleotide polymorphism (SNP) rs7553007 in liver metastasis on the CRC-specific survival (CSS) of patients after colorectal liver metastasectomy.
  
  
  RESULTS
  We found no significant differences in genotype distributions and allele frequencies at the CRP SNP rs7553007 between CRC patients with liver metastasis and the control group. CSS rates were low in the subgroup of patients with synchronous metastasis with the A-allele (A/A and A/G) at rs7553007 or mutated KRAS/BRAF in liver metastatic specimens. Furthermore, the CRP SNP rs7553007 (hazard ratio [HR] = 1.101; 95% confidence interval [CI] = 1.011-1.200; P = 0.027) and KRAS/BRAF mutations (HR = 2.377; 95% CI = 1.293-4.368; P = 0.005) remained predictive for the CSS of CRC patients with synchronous liver metastasis in multivariate analysis.
  
  
  CONCLUSIONS
  Both the CRP SNP rs7553007 and KRAS/BRAF mutations were independent prognostic factors for CRC patients with synchronous liver metastasis.
authors.affiliation: Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Huang
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Teng
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chien
authors.forename: Jen-Kou
authors.initials: JK
authors.lastname: Lin
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012044:Regression Analysis; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D002097:C-Reactive Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins