Role of CYP2E1 polymorphisms in breast cancer: a systematic review and meta-analysis

Abstract

BackgroundCYP2E1 polymorphisms have been reported to influence individual’s breast cancer susceptibility as a phase I enzyme, but the results of these previous studies remain controversial. We performed a comprehensive meta-analysis to assess their association.MethodsA comprehensive search of literature included in various databases (PubMed, Web of Science and Google scholar), published before August 2016, was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the associations between three polymorphisms of CYP2E1 and breast cancer susceptibility. Subgroup analysis, sensitivity analysis and test for publication bias were also performed. A total of 11 separate comparisons involving 4311 cases and 4407 controls were included in the meta-analysis.ResultsOur result showed that there was no significant association between the two common polymorphisms CYP2E1 rs2031920 C>T, CYP2E1*5 Rsa I/Rst I (c1/c2) and BC risk. For CYP2E1*6 Dra I (D/C) polymorphism, a significantly increased BC risk in the overall population was found in genetic model D/C vs. D/D (OR = 1.29, 95% CI = 1.04–1.61, P = 0.023) and C/C + D/C vs. D/D (OR = 1.25, 95% CI = 1.04–1.51, P = 0.019), together with subjects who have at least one C allele (C vs. D: OR = 1.46, 95% CI = 1.20–1.79, P < 0.001). Similar results were also found in subgroup analyses in Caucasians of these three comparison models.ConclusionsThe present meta-analysis suggests that CYP2E1*6 Dra I (D/C) variation significantly associated with the risk of BC. Individuals with D/C and C/C + D/C genotypes or carried at least one C allele of CYP2E1*6 Dra I (D/C) polymorphism had a significant higher susceptibility to develop BC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0371-9) contains supplementary material, which is available to authorized users.

CYP2D6 and CYP2E1 Gene Polymorphisms and their Association with Cervical Cancer Susceptibility: A Hospital Based Case-Control Study from South-Western Maharashtra

“…When we considered CYP2E1 polymorphisms, the results from our study presented the involvement of variant A or *6 allele of CYP2E1*6 in the susceptibility of CC (OR=4.81; 95% CI: 1.57-14.77; p=0.005) in the rural population of South-Western Maharashtra, which is not reported earlier by any of the researcher. Our results are consistent with other reports where role of CYP2E1*6 has been discussed with susceptibility to other cancers (Chong et al, 2016;Lu et al, 2017). The results from this study also signified that CYP2E1*5B and CYP2E1*7B polymorphisms were not associated with CC risk in studied rural population however, heterozygous G/T genotype of CYP2E1*7B showed negative association with CC development (OR=0.43; 95% CI: 0.28 -0.67; p=0.0002).…”

“…2 Department of Oncology Krishna Institute of Medical Sciences "Deemed to be University" Taluka-Karad, Dist-Satara, Pin-415 539, Maharashtra, India. *For Correspondence: hodgeneticslab@kimskarad.in increased or decreased susceptibility to several cancers including esophagus, lung and colorectal cancer (Leng et al, 2012;Shahriary et al, 2012;Jiang et al, 2013;Shen et al, 2015;Zeng et al, 2017) and more recently breast (Lu et al, 2017), bladder (Yin et al, 2018 and head and neck cancer (Farhat et al, 2020;Aday et al, 2021). Few Indian studies also noted association of CYP2D6 polymorphism with breast cancer risk in South Indian population (Surekha et al, 2010).…”

Polymorphisms of drug-metabolizing enzyme CYP2E1 in Chinese Uygur population

“…So far, more than 100 SNPs have been found in CYP2E1 but only several might alter the enzyme activity. [ 16 ] According to the racial comparison, the CYP2E1 gene shows genetic polymorphisms that vary markedly in their frequency among different ethnic populations. Among them, linkage disequilibrium of rs2031920 and rs3813867 leads to the CYP2E1 ∗ 5B haplotype and was associated with restriction enzyme sites RsaI and PstI.…”

Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

“…Furthermore, evidence also suggests that CYP2E1 regulates cellular energy metabolism in a manner dependent on cell type and potentially on the clinical staging of the disease and suggest a possible biomarker role [ 78 ]. The genetic polymorphic variant CYP2E1 *6 Dra1 (D/C) has also been shown to correlate with higher risk of developing breast cancer and warrants further investigation [ 79 ].…”