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AHR gene expression and the polymorphism rs2066853 are associated with clinicopathological parameters in colorectal carcinoma.

T. Cheng,S. Gamage,D. Hewage,Cu-Tai Lu,V. Gopalan,A. Lam

Published 2022 in Human Pathology

ABSTRACT

The relationship between red and processed meat and its risk towards colorectal carcinoma (CRC) is not fully explored in literature. Polycyclic aromatic hydrocarbons (PAHs) are pro-carcinogenic molecules that are ingested with meat cooked at high temperatures. The metabolic conversion of PAHs to carcinogenic diol epoxides is in part mediated by the aryl hydrocarbon receptor (AhR)-dependent induction of CYP1A1. This study aims to examine and expression profiles and polymorphisms of the AHR (aryl hydrocarbon receptor) gene which is involved in the metabolic conversion of PAHs in patients with CRC. Genetic analysis was done in matched cancer and non-neoplastic tissues from 79 patients diagnosed with CRCs. Low AHR mRNA expression was associated mucinous colorectal adenocarcinoma. Exon 10 of AHR showed that 27% of patients had the rs2066853 single nucleotide polymorphism resulting in an arginine to lysine change at codon 554. This variant was significantly associated with a lower likelihood of perineural invasion, presence of synchronous cancer, and multiple colorectal polyps. Furthermore, rs2066853 individuals were significantly more likely to be of more advanced age and have a more favourable tumour grade and pathological stage. These results imply the pathogenic roles of AHR in PAH-associated colorectal carcinogenesis.

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