Lack of association between multiple polymorphisms in aryl hydrocarbon receptor (AhR) gene and cancer susceptibility

Abstract

Background The aryl hydrocarbon receptor (AhR) is commonly known as an environmental sensor. Polymorphisms in AhR gene have been implicated in susceptibility to cancer. However, the results were controversial. This study was conducted to quantitatively summarize the association between AhR polymorphisms and cancer risk by meta-analysis. Methods Relevant reports were searched in four databases (Embase, PubMed, Wanfang, and China National Knowledge Infrastructure). We used pooled odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the strength of the association in both standard and cumulative meta-analysis. Subgroup and sensitivity analysis was also performed, and between-study heterogeneity and publication bias were checked. Results A total of seventeen studies referring to three AhR polymorphisms (rs2066853, rs7796976, and rs2074113) were identified, and 9557 cases and 10038 controls were included. There was no statistically significant association of AhR rs2066853 polymorphism with cancer risk in the overall population, and the negative results were repeated in subgroup analysis by the ethnicity and cancer type. Concerning AhR rs7796976 or rs2074113 polymorphism, no significant correlation was detected. Moreover, these non-significant findings were stable in sensitivity analysis, and the cumulative meta-analysis indicated a trend of no significant link between this three AhR polymorphisms and cancer risk as more data accumulated over time. Conclusion This meta-analysis provides evidence that the rs2066853, rs7796976, or rs2074113 polymorphism in AhR gene is not a susceptible predictor of cancer. Further clinical and functional investigation between AhR polymorphisms and cancer susceptibility are needed.

Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population

“…On the other hand, previous data have demonstrated no statistically significant association of AhR (rs2066853) polymorphism with cancer risk [37,46]. A recent meta-analysis has reported that ethnicity and cancer type might be the source of the reported heterogeneity related to (rs2066853) polymorphism implication [12]. In the Tunisian population, there is a mosaic genetic structure, with the majority of the Eurasian lineages (Caucasians), followed by the Sub-Saharan and North African lineages.…”

“…This induces the upregulation of phase I and II enzymes, such as cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase (GST), which are involved in PAH metabolism [11]. Moreover, several reports have indicated that the functions of AhR may be influenced by the presence of genetic polymorphisms [12]. In this context, the c.G1661A single nucleotide polymorphism (SNP) (p.Arg554Lys; rs2066853) of the AhR gene was identified by Kawajiri et al(1995) [13] as the most commonly studied polymorphism with malignancies including lung, breast, colorectal, and bladder cancers [14].…”

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

“…Rs2066853 does not confer colorectal polyp [42] or colorectal cancer [43] risk, nor was it associated with pancreatic cancer [44] or Crohn's disease [45]. A meta-analysis showed that rs2066853 was not associated with breast, lung, or overall cancer risk [24]. In addition, rs2066853 has been associated with increased disease aggressiveness in patients with acromegaly [46], increased likelihood of oligoasthenospermia [25], and a higher risk or glioma [47].…”

“…Relationships between functional polymorphisms of AHR and cancer, particularly CRC, are not well established and requires further investigation [24]. rs2066853 is the most studied single nucleotide polymorphism (SNP) of AHR, and describes a G to A transition in exon 10 at position 1661(c.1661G>A) on the coding DNA strand [25].…”