Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common in women Amirifard et al., 2016. There are very few studies about KRAS mutations in CRC from developing countries such as Iran Bishehsari et al., 2006. The latest data from the cancer patients’ registry program showed that the age-standardized incidence rate had risen from 2.8 to 5.5 in 2009 and reached 9.2 in 2012 per 100,000 persons Dolatkhah et al., 2016. KRAS is a proto-oncogene located on the short arm of chromosome 12, encodes the protein KRAS, a GTPase involved in cell division, differentiation and apoptosis Dobre et al., 2015. The prevalence of KRAS mutation in CRC patients is 35–40 %, and the majority of these mutations occur in codon 12 and less frequently in codon 13 of KRAS gene Rosty et al., 2013. Mutations activating the KRAS proto-oncogene are considered a key step in the progression from normal colorectal epithelium to carcinoma Fearon and Vogelstein, 1990. Roughly 90% of the activating mutations, that are influential solitary amino acid replacement in the GTPase pocket that guide to a block of the activity of KRAS p21 protein, are recognized in codons 12 (GGT) and 13 (GGC) of exon 1 and almost 5% in codon 61 (CAA) situated in exon 2. The most regularly found kinds of mutations are G>A and G>T transitions Palmirotta et al., 2009. This meta-analysis study aimed to indicate the prevalence of KRAS mutations in CRC patients in Iran.

From the initial 82 articles identified from the search, after excluding the studies, 18 studies were assessed for eligibility. Then, seven studies were excluded based on reasons. At last, eleven studies included and analyzed for meta-analysis study ( Figure 1 ).

The characteristics of the studies included in the meta-analysis are shown in Table 1 . All studies are case-control studies published between 2006 and 2016. Six studies were studied from Tehran (Central of Iran) Bishehsari et al., 2006Roudbari et al., 2016Shemirani et al., 2011Sobhani et al., 2010Tameshkel et al., 2016Vakil et al., 2016, one study from Shiraz (Southwest of Iran) Omidifar et al., 2015, two studies from Kermanshah (Western of Iran) Amirifard et al., 2016Payandeh et al., 2016, one study from Tabriz (Northwestern of Iran) Dolatkhah et al., 2016, and one study from South Khorasan (Eastern of Iran) Naseri et al., 2016. All studies included 1814 CRC patients that mean age of the patients was 57.5 years. In more studies, the prevalence of CRC in males was more than females Amirifard et al., 2016Bishehsari et al., 2006Dolatkhah et al., 2016Naseri et al., 2016Omidifar et al., 2015Payandeh et al., 2016Roudbari et al., 2016Shemirani et al., 2011Tameshkel et al., 2016Vakil et al., 2016. Number of mutations in codon 12 and 13 and also mutant amino acid in codon 12 has been shown in Table 1 that Gly is normal amino acid in codon 12 and can change to other amino acids.

More studies were not sex-matched.

Some studies reported the prevalence just in metastatic CRC and rest of studies both metastatic and non-metastatic CRC.

The studies reported in different areas and races of Iran that geographical area and race can effect on the prevalence of mutations.

In a number of studies, except for codon 12 and 13, types of other different codons have been checked.

The meta-analysis showed that the prevalence of KRAS mutation in Iran was different with more studies that therefore the geographical area and race can impact on the prevalence of KRAS mutation in CRC patients. Also, Codon 12 had the most prevalence among mutant codons, followed by codon 13. At last, Gly to Asp and Gly to Val were the most mutations in codon 12.

CI: Confidence Interval

CRC: Colorectal Cancer

ER: Event Rate

SID: Scientific Information Database

Conceptualization: MP ES MS

Data curation: ES MS

Formal analysis: ES MS

Funding acquisition: ES MS

Investigation: NA BS NF

Methodology: ES MS

Project administration: MP NA BS NF

Resources: MP MD

Software: ES MS

Supervision: MP NA

Validation: MP ES MS

Visualization: NA BS NF

Writing – original draft: ES MS

Writing – review & editing: MP NA MS BS NF ES MD