Lack of association between the aryl hydrocarbon receptor rs2066853 polymorphism and breast cancer: A meta-analysis on Ahr polymorphism and breast cancer

Y, Li; Hz, Qin; Song, Qi; Xd, Wu; Zhu, Jun

doi:10.4238/2015.december.8.5

Cited by 4 publications

(5 citation statements)

References 19 publications

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“…6). The usage of accumulative metaanalysis and the relatively larger sample size made the current meta-analysis more precise and comprehensive, but the results of rs2066853 polymorphism were in agreement with those in the previous meta-analysis [15]. The rs2066853 site, located in the transactivation domain of AhR gene, could result in a nonsynonymous amino acid substitution and influence the function of AhR protein [12].…”

Section: Discussionsupporting

confidence: 79%

“…Meta-analysis is a valuable quantitative means to pool data from different studies and enhance statistical power, thereby overcoming the limitations of individual studies and achieving more reliable conclusions. Although two meta-analyses of AhR polymorphisms with cancer risk have been carried out [15,16], the following reasons impelled us to update them: (1) one previous metaanalysis merely focused on the correlation between AhR rs2066853 polymorphism and the risk of breast cancer using three original studies [15]; (2) several case-control, cohort, or cross-sectional studies published in recent years have not been included in either of the above metaanalyses; (3) there was no subgroup analysis of ethnicity in the previous meta-analyses [15,16], probably because of inadequate original studies; and (4) cumulative metaanalysis, which could estimate the trend and robustness of the pooled results, has not been performed in either of the previous meta-analyses. Accordingly, in the present study, meta-analysis with the most updated data was performed to explore whether AhR polymorphisms confer susceptibility to cancer.…”

Section: Introductionmentioning

confidence: 99%

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

Luo

Wang

et al. 2020

Environ Health Prev Med

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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.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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

Luo

Wang

et al. 2020

Environ Health Prev Med

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“…While the role of CYP1A2 rs762551 with respect to breast cancer risk seems weak or non-significant [ 52 ], unless coffee consumption was taken into account [ 34 , 53 ]. A meta-analysis showed that the association between the AhR Arg554Lys and breast cancer risk differs between studies of women with different ethnicities, although the overall result was no association [ 54 ]. The CYP1A2 rs762551 is associated with the metabolism of several drugs and also with efficacy and toxicity [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

CYP1A2 – a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients

et al. 2016

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BackgroundEndocrine resistance is a major obstacle to optimal treatment effect in breast cancer. Some genetic markers have been proposed to predict response to aromatase inhibitors (AIs) but the data is insufficient. The aim of the study was to find new genetic treatment predictive markers of AIs.MethodsThe ongoing population-based BC-blood study in Lund, Sweden includes women with primary breast cancer. This paper is based on AI-treated patients with estrogen receptor positive tumors who underwent breast cancer surgery in 2002–2008. First, an exploratory analysis of 1931 SNPs in 227 genes involved in absorption, distribution, metabolism, and elimination of multiple medications, using DMET™ chips, was conducted in a subset of the cohort with last follow-up in December 31st 2011 (13 cases, 11 controls). Second, selected SNPs from the first analysis were re-analyzed concerning risk for early breast cancer events in the extended cohort of 201 AI-treated with last follow-up in June 30th 2014. Clinical data were obtained from medical records and population registries.ResultsOnly CYP1A2 rs762551 C-allele was significantly associated with increased risk for early events in the 24 patients (P = 0.0007) and in the extended cohort, adjusted Hazard ratio (HR) 2.22 (95 % CI 1.03–4.80). However, the main prognostic impact was found within five years, adjusted HR 7.88 (95 % CI 2.13–29.19). The impact of the CYP1A2 rs762551 C-allele was modified by a functional polymorphism in the regulator gene AhR Arg554Lys (G > A). Compared to patients who were homozygous for the major allele in both genes (CYP1A2 A/A and AhR G/G), a 9-fold risk for early events was found in patients who had at least one minor allele in both genes, adjusted HR 8.95 (95 % CI 2.55–31.35), whereas patients with at least one minor allele in either but not both genes had a 3-fold risk for early events, adjusted HR 2.81 (95 % CI 1.07–7.33). The impact of CYP1A2 rs762551 C-allele was also modified by the CYP19A1 rs4646 C/C, adjusted HR 3.39 (95 % CI 1.60–7.16) for this combination. This association was strongest within the first five years, adjusted HR 10.42 (95 % CI 3.45–31.51).ConclusionCYP1A2 rs762551 was identified as a new potential predictive marker for early breast cancer events in AI-treated breast cancer patients. Moreover, combined genotypes of CYP1A2 rs762551 and CYP19A1 rs4646 or AhR Arg554Lys could further improve prediction of early AI-treatment response. If confirmed, these results may provide a way to more personalized medicine.

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“…chronic exposure to low doses of environmental pollutants promotes cancer metastasis and generates chemoresistance through epithelial-mesenchymal transition (eMT) and cancer stemness (the stem cell-like phenotype in tumors) (66). However, another meta-analysis demonstrates that ahr (rs2066853) polymorphism does not modify the risk of breast cancer (67). These findings suggest that ahr may be a promising potential drug target for breast cancer treatment.…”

Section: Association Between Ahr and Breast Cancermentioning

confidence: 99%

Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review)

Chen,

Wang,

Liao

et al. 2023

Mol Med Rep

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Breast cancer is the most common malignancy in women. Metastatic breast cancer is incurable and is a major cause of shortened patient survival. The different molecular types of breast cancer make targeted therapy difficult and a complex challenge. aryl hydrocarbon receptor (ahr) is an evolutionarily conserved transcription factor that has been implicated in the metabolism of xenobiotic ligands. ahr is activated by numerous exogenous and endogenous ligands and participates in multiple physiological processes, including proliferation, migration, invasion and apoptosis. ahr expression is upregulated in certain breast cancer subtypes, including estrogen receptor-positive breast cancer, and has been implicated in the development and progression of breast cancer. over the last two decades, ahr and its ligands have emerged as novel biological targets for the treatment of breast cancer. Both ahr agonists and antagonists may be effective in inhibiting critical activities of breast cancer. The present review evaluates the role and underlying mechanisms of ahr and its ligands in breast cancer and demonstrates the potential of exploiting ahr as a novel target for breast cancer therapy. Contents1. introduction 2. association between ahr and breast cancer 3. ahr pathways in breast cancer 4. ahr ligands exhibit tumor-suppressive properties 5. ahr and its ligands promote mammary carcinogenesis 6. discussion 7. conclusion

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Lack of association between the aryl hydrocarbon receptor rs2066853 polymorphism and breast cancer: A meta-analysis on Ahr polymorphism and breast cancer

Cited by 4 publications

References 19 publications

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

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

CYP1A2 – a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients

Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review)

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