Abstract
Colorectal cancer (CRC) is the fourth most common cause of cancer death in the world. Genetic variants in 8q24.21 including rs10505477 and rs6983267 have been hypothesized to be involved in susceptibility to CRC. This study aims to investigate the possible association between these loci and their haplotypes with CRC risk in Iranian population. Subjects were recruited from two hospitals in Tehran. The rs10505477 and rs6983267 polymorphisms were genotyped by TaqMan real time PCR using subject genomic DNA, extracted either from formalin-fixed, paraffin-embedded tissue of patients or from blood of the controls by standard methods. A total of 715 subjects (380 CRC patients and 335 matched controls) were genotyped in this study. Allele and genotype analysis of the rs10505477 and rs6983267 polymorphisms by gender, age at diagnosis, tumor location, tumor grade, and tumor node metastasis (TNM) showed no significant association with CRC risk. There was a significant relationship between GG haplotype and susceptibility to age at diagnosis for both <60 and ≥60 (p=0.0005 and p=0.000004, respectively) and between GT and CRC in the age at diagnosis ≥ 60 (Table 3: p=0.031). The GG haplotype was less frequent in CRC patients with the age at diagnosis <60, but was more common in subjects with the age at diagnosis ≥ 60. Results of this study suggests that the rs6983267 and rs10505477 polymorphisms alone may not be relevant to CRC risk, but their GG haplotype plays a notable role in age at diagnosis of CRC in the Iranian population.
Highlights
Colorectal cancer (CRC) is a major public health problem in the world wide and is considered as the second most common cause of cancer death in the western
Evidence identified a strong association between rs6983267 and rs10505477 genetic markers in chromosome 8q24.21 and risk of some types of cancers such as CRC
The rs10505477 locus lies in a hotspot within a 1.5-Mb gene-free region with a distance of 5.90 kbp from rs6983267 polymorphism located in the putative MYC regulatory element which has been suggested as a causal variant for CRC (Tomlinson et al, 2007; Zanke et al, 2007; Tenesa et al, 2008; Haerian et al, 2011)
Summary
Colorectal cancer (CRC) is a major public health problem in the world wide and is considered as the second most common cause of cancer death in the western. This disease is the second most common cancer in female and the third in male in the world. Results: A total of 715 subjects (380 CRC patients and 335 matched controls) were genotyped in this study. The GG haplotype was less frequent in CRC patients with the age at diagnosis
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