Yari Abolfazl, Afzali Asiyeh, Aalipour Mostafa, Nakheai Mehran, Zahedi Mohammad Javad
Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
Department of Medical Genetics, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Caspian J Intern Med. 2020 Fall;11(4):355-369. doi: 10.22088/cjim.11.4.355.
Mutations in the EGFR signaling pathway play an important role in the development of colorectal cancer (CRC). Mutations in these genes, like KRAS and BRAF, affect the treatment strategies and associated with poor prognosis and relative resistance to anti-EGFR therapies. Our aim was to conduct a systematic and meta-analysis on all studies that have been conducted on the prevalence of these gene mutations in Iranian CRC patients.
Four science citation index databases (MEDLINE, EMBASE, Web of Science and Cochrane library) and local databases were searched up to March 2018 with related keywords. Two reviewers independently screened and extracted the data. Quality of all included studies was assessed using an adapted checklist from STROBE. A random-effect model was used to calculate the total prevalence of KRAS and BRAF mutations in CRC subjects by the event rate (ER). Meta-regression was utilized to explore heterogeneity causes.
In total, from 573 records, 23 eligible studies (2662 patients) were included for data extraction and analysis. In 18 of 23 included studies, the prevalence of KRAS mutations was 33.9% (95% CI=30.1-37.9) with I2=65.17 (p<0.001). The occurrence of KRAS mutations in codon 12 and 13 was 76.9% (95% CI = 70.4-82.3%) with I2=84.88 (p<0.001) and 23.5% (95% CI=17.9-30.3) with I2=85.85 (p<0.001), respectively. In 9 of 23 studies, the BRAF mutation rate was 3.2% (95% CI=0.003-13.6) with I2=88.61 (p<0.001).
The prevalence of these mutations in CRC patients shows a significant difference in the different regions of Iran, which is probably due to environmental and racial factors.
表皮生长因子受体（EGFR）信号通路突变在结直肠癌（CRC）的发生发展中起重要作用。这些基因如KRAS和BRAF的突变会影响治疗策略，且与预后不良及抗EGFR治疗的相对耐药相关。我们的目的是对所有关于伊朗CRC患者中这些基因突变发生率的研究进行系统分析和荟萃分析。
截至2018年3月，使用相关关键词检索了四个科学引文索引数据库（MEDLINE、EMBASE、科学网和考克兰图书馆）以及本地数据库。两名评审员独立筛选并提取数据。使用从STROBE改编的清单评估所有纳入研究的质量。采用随机效应模型通过事件发生率（ER）计算CRC受试者中KRAS和BRAF突变的总发生率。利用荟萃回归探索异质性原因。
总共从573条记录中纳入了23项符合条件的研究（2662例患者）进行数据提取和分析。在23项纳入研究中的18项中，KRAS突变发生率为33.9%（95%可信区间=30.1 - 37.9），I² = 65.17（p < 0.001）。密码子12和13处KRAS突变的发生率分别为76.9%（95%可信区间 = 70.4 - 82.3%），I² = 84.88（p < 0.001）和23.5%（95%可信区间 = 17.9 - 30.3），I² = 85.85（p < 0.001）。在23项研究中的9项中，BRAF突变率为3.2%（95%可信区间 = 0.003 - 13.6），I² = 88.61（p < 0.001）。
这些突变在CRC患者中的发生率在伊朗不同地区存在显著差异，这可能是由于环境和种族因素所致。
