Association of 8q24.21 rs10505477-rs6983267 Haplotype and Age at Diagnosis of Colorectal Cancer

Abstract

<b>Background:</b> Colorectal cancer (CRC) is the fourth most common cause of cancer death in the world. Geneticvariants in 8q24.21 including rs10505477 and rs6983267 have been hypothesized to be involved in susceptibilityto CRC. This study aims to investigate the possible association between these loci and their haplotypes with CRCrisk in Iranian population. Materials and <br/><b>Methods</b>: Subjects were recruited from two hospitals in Tehran. Thers10505477 and rs6983267 polymorphisms were genotyped by TaqMan real time PCR using subject genomicDNA, extracted either from formalin-fixed, paraffin-embedded tissue of patients or from blood of the controls bystandard methods. <br/><b>Results</b>: A total of 715 subjects (380 CRC patients and 335 matched controls) were genotypedin this study. Allele and genotype analysis of the rs10505477 and rs6983267 polymorphisms by gender, age atdiagnosis, tumor location, tumor grade, and tumor node metastasis (TNM) showed no significant associationwith CRC risk. There was a significant relationship between GG haplotype and susceptibility to age at diagnosisfor 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, butwas more common in subjects with the age at diagnosis ≥ 60. <br/><b>Conclusions</b>: Results of this study suggests thatthe rs6983267 and rs10505477 polymorphisms alone may not be relevant to CRC risk, but their GG haplotypeplays a notable role in age at diagnosis of CRC in the Iranian population.