title: Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the third-most common cancer in Iran. The increasing incidence of CRC in the past three decades has made it a major public health burden in the country. This study aimed to determine any relationship of specific mutations in CRCs with clinicopathologic aspects and outcome of patients.
  
  
  METHODS
  This study was conducted on 100 CRC patients by the case-only method. Polymerase chain-reaction products were analyzed by Sanger sequencing, and sequence results were compared with the significantKRASandBRAFgene mutations in the My Cancer Genome database. Logistic regression models were used to detect associations of clinicopathologic characteristics with each of the mutations. Kaplan-Meier and Cox regression models were constructed to estimate overall survival in patients.
  
  
  RESULTS
  A total of 26 subjects (26%) had heterozygote-mutantKRAS, and mutations were not detected in the amplified exon ofBRAFin both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood ofKRASmutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood ofKRASmutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients withKRASwild-type cancers, those withKRASmutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44-9.68; log-rankP=0.003).
  
  
  CONCLUSIONS
  Better understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease.
authors.affiliation: Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Roya
authors.initials: R
authors.lastname: Dolatkhah
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Somi
authors.affiliation: Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Iraj
authors.initials: I
authors.lastname: Asvadi Kermani
authors.affiliation: Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Bonyadi
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Sepehri
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Kamal
authors.initials: K
authors.lastname: Boostani
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Saleh
authors.initials: S
authors.lastname: Azadbakht
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nikou
authors.initials: N
authors.lastname: Fotouhi
authors.affiliation: Molecular Medicine Laboratory, University of Kansas Medical School, Kansas City, KS, USA.
authors.forename: Faris
authors.initials: F
authors.lastname: Farassati
authors.affiliation: Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Tabriz Health Services Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Dastgiri
keywords: colorectal cancer; proto-oncogene; regression; sequence analysis; survival