Molecular markers and pathway analysis of colorectal carcinoma in the Middle East

Abstract

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. A newly proposed integrated pathway comprising traditional, alternate, and serrated pathways by genetic and epigenetic factors was defined recently and hypothesized to play a role in the pathogenesis of CRC; however, to the authors' knowledge, there is a paucity of information regarding these proposed molecular pathways in different ethnic groups. METHODS: Molecular characterization of 770 CRC specimens was performed for microsatellite instability, BRAF, and KRAS by polymerase chain reaction and 500 cases for CpG island methylator phenotype (CIMP) high phenotype by MethyLight technology. Tumors were assigned to different molecular pathways and examined for clinicopathological correlation and survival analysis. RESULTS: The traditional pathway constituted 33.4% of CRC cases, the alternate pathway comprised 11.6%, and the serrated molecular pathway accounted for only 0.8% of Middle Eastern CRC cases. Approximately 54.2% of CRC cases did not qualify to fit into any pathway and thus were designated as an unassigned group. Molecular pathways were found to be significantly associated with tumor site and grade. A subset of cases with an uncategorized pathway demonstrated a significant survival difference (P 5 .0079). CONCLUSIONS: The serrated pathway was found to account for a very low percentage of the CRC patient cohort in the current study. The unassigned group accounted for the majority of Middle Eastern CRC cases, and therefore methods of CRC pathway analysis might not be applicable to this ethnic group. The current study demonstrates the need to unravel the molecular genetic basis of this disease to further subcategorize these CRC cases. It also identifies a need for further studies on different populations for a better understanding of their exact role and incidence. Cancer 2015;121:3799-808.

Reply to specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations

“…We would like to thank the authors for showing interest in our recently published work on colorectal cancer (CRC) and also for highlighting the importance of this study in CRC occurring in a Middle Eastern population . We agree with the authors regarding the known etiology of CRC, which is complex and multifactorial and includes genetic, environmental, and lifestyle factors that contribute to its development.…”

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

“…The largest study, which included 500 patients from Saudi Arabia, assessed KRAS and BRAF using polymerase chain reaction (PCR) and DNA sequencing; the reported frequency rates were 30.1% and 2.4%, respectively (24). However, no studies have utilized next-generation sequencing (NGS) to assess in-depth mutations in Arab patients with CRC.…”

Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes

“…Previous studies from the Middle East (or in the Arab population) that enrolled a relatively large number of patients and included patients with different stages of the disease, reported K-ras mutation rates of 28-56% in Saudi Arabia (Abubaker et al, 2009;Zahrani et al, 2014;Beg et al, 2015;Dallol et al, 2016), 33-45% in Turkey (Gumus et al, 2013;Baskin et al, 2014), and 33-44% in Jordan (Elbjeirami and Sughayer, 2012;Gumus et al, 2013). Lower mutation rates were observed in countries to the west of Saudi Arabia, such as Egypt (11-18%) (Soliman et al, 2001;Gumus et al, 2013), and Morocco (24%) (Marchoudi et al, 2013).…”