Dolatkhah Roya, Somi Mohammad Hossein, Asvadi Kermani Iraj, Bonyadi Morteza, Sepehri Bita, Boostani Kamal, Azadbakht Saleh, Fotouhi Nikou, Farassati Faris, Dastgiri Saeed
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Onco Targets Ther. 2016 Dec 7;9:7385-7395. doi: 10.2147/OTT.S116373. eCollection 2016.
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.
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 and 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.
A total of 26 subjects (26%) had heterozygote-mutant , and mutations were not detected in the amplified exon of in both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood of mutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood of mutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients with wild-type cancers, those with mutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44-9.68; log-rank =0.003).
Better understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease.
结直肠癌(CRC)是伊朗第三大常见癌症。在过去三十年中,CRC发病率不断上升,已成为该国的一项重大公共卫生负担。本研究旨在确定CRC中特定突变与患者临床病理特征及预后之间的关系。
本研究采用病例对照法对100例CRC患者进行研究。通过桑格测序分析聚合酶链反应产物,并将序列结果与My Cancer Genome数据库中的重要基因突变进行比较。采用逻辑回归模型检测临床病理特征与每种突变之间的关联。构建Kaplan-Meier和Cox回归模型来估计患者的总生存期。
共有26名受试者(26%)存在杂合子突变,在100例CRC的肿瘤组织和正常组织的扩增外显子中均未检测到突变。直肠肿瘤发生突变的可能性比结肠肿瘤高1.53倍,男性发生突变的几率比女性高1.37倍。与非转移性CRC患者相比,发生转移的患者发生突变的可能性增加2.36倍。与野生型癌症患者相比,发生突变的患者死亡率显著更高(风险比3.74,95%置信区间1.44 - 9.68;对数秩检验=0.003)。
通过结合流行病学和疾病分子机制研究,可以更好地了解CRC的病因。