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Abstract
BackgroundThe 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.MethodsRelevant 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.ResultsA 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.ConclusionThis 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.
Highlights
It is well recognized that cancer is a major public health issue, and an estimated 18.1 million new cancer cases and 9.6 million cancer deaths occurred in 2018 globally based on the GLOBOCAN data [1]
The selected characteristics of the original studies and genotype distributions of aryl hydrocarbon receptor (AhR) polymorphisms were illustrated in Tables 1 and 2, respectively
Evidence from our meta-analysis suggests that AhR rs2066853 polymorphism is not a risk factor for cancer either in the overall population, Caucasians, Asians, or Chinese, and this polymorphism is not a risk factor for lung cancer or breast cancer
Summary
It is well recognized that cancer is a major public health issue, and an estimated 18.1 million new cancer cases and 9.6 million cancer deaths occurred in 2018 globally based on the GLOBOCAN data [1]. The exact mechanism of carcinogenesis is complex and not fully elucidated, but it has become clear that cancer links to the interaction between genetic factors and environmental exposure, such as lifestyle and chemical contaminants. Polycyclic aromatic hydrocarbons (PAHs) belong to the common environmental contaminants, and numerous PAHs are known as carcinogens [2]. The carcinogenic risk of environmental substances depends on the exposure dose, and on personal susceptibility to the carcinogens [3]. The aryl hydrocarbon receptor (AhR) is commonly known as an environmental sensor. Polymorphisms in AhR gene have been implicated in susceptibility to cancer. This study was conducted to quantitatively summarize the association between AhR polymorphisms and cancer risk by meta-analysis
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