Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran

• Main Authors: Dolatkhah R, Somi MH, Asvadi Kermani I, Bonyadi M, Sepehri B, Boostani K, Azadbakht S, Fotouhi N, Farassati F, Dastgiri S
• Format: Article
• Language: English
• Published: Dove Medical Press 2016-12-01
• Series: OncoTargets and Therapy
• Subjects: Proto-Oncogene; Sequence Analysis; Regression; Colorectal Cancer; Survival
• Online Access: https://www.dovepress.com/association-between-proto-oncogene-mutations-and-clinicopathologic-cha-peer-reviewed-article-OTT

Roya Dolatkhah,1 Mohammad Hossein Somi,2 Iraj Asvadi Kermani,1 Morteza Bonyadi,3 Bita Sepehri,2 Kamal Boostani,2 Saleh Azadbakht,2 Nikou Fotouhi,2 Faris Farassati,4 Saeed Dastgiri1,5 1Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 3Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; 4Molecular Medicine Laboratory, University of Kansas Medical School, Kansas City, KS, USA; 5Tabriz Health Services Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 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. Materials and 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 significant KRAS and BRAF gene 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-mutant KRAS, and mutations were not detected in the amplified exon of BRAF in both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood of KRAS mutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood of KRAS mutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients with KRAS wild-type cancers, those with KRAS mutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44–9.68; log-rank P=0.003). Conclusion: Better understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease. Keywords: proto-oncogene, sequence analysis, regression, colorectal cancer, survival