Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses

Abstract

BackgroundPolymorphisms in the CYP1A2 genes have the potential to affect the individual capacity to convert pre-carcinogens into carcinogens. With these comprehensive meta-analyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on CYP1A2 single nucleotide polymorphisms (SNPs) and the risk of cancer.MethodsWe searched MEDLINE, ISI Web of Science and SCOPUS bibliographic online databases and databases of genome-wide association studies (GWAS). After data extraction, we calculated Odds Ratios (ORs) and 95 % confidence intervals (CIs) for the association between the retrieved CYP1A2 SNPs and cancer. Random effect model was used to calculate the pooled ORs. Begg and Egger tests, one-way sensitivity analysis were performed, when appropriate. We conducted stratified analyses by study design, sample size, ethnicity and tumour site.ResultsSeventy case-control studies and one GWA study detailing on six different SNPs were included. Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls. The meta-analysis of 62 studies on rs762551, reported an OR of 1.03 (95 % CI, 0.96–1.12) for overall cancer (P for heterogeneity < 0.01; I2 = 50.4 %). When stratifying for tumour site, an OR of 0.84 (95 % CI, 0.70–1.01; P for heterogeneity = 0.23, I2 = 28.5 %) was reported for bladder cancer for those homozygous mutant of rs762551. An OR of 0.79 (95 % CI, 0.65–0.95; P for heterogeneity = 0.09, I2 = 58.1 %) was obtained for the bladder cancer from the hospital-based studies and on Caucasians.ConclusionsThis large meta-analysis suggests no significant effect of the investigated CYP1A2 SNPs on cancer overall risk under various genetic models. However, when stratifying according to the tumour site, our results showed a borderline not significant OR of 0.84 (95 % CI, 0.70–1.01) for bladder cancer for those homozygous mutant of rs762551. Due to the limitations of our meta-analyses, the results should be interpreted with attention and need to be further confirmed by high-quality studies, for all the potential CYP1A2 SNPs.

Immunohistological expression of cytochrome P450 1A2 (CYP1A2) in the ovarian follicles of prepubertal and pubertal rat

“…CYP1A subfamily contains only two functional isoforms as CYP1A1 and CY-P1A2, and it has been addressed that CYP1A2 is expressed mainly in the liver; whereas the expression of CYP1A1 is mainly distributed outside the liver and involves the metabolism for aromatic hydrocarbon, CYP1A2 is expressed in the liver and metabolizes the aromatic amines and heterocyclic compounds (Wijnen et al, 2007;Lee et al, 2012;Lu et al, 2020). However, in recent days, the expression of CYP1A2 is identified in the pancreas and lung as well (Vukovic et al, 2016). Likewise, the detection of CYP1A2 expression in other tissues has been investigating to understand its function at each organ.…”

Lack of Association of CYP2C9 genetic polymorphism with oral squamous cell carcinoma

“…However, our study could not nd any association of CYP2C9 genetic polymorphisms with OSCC. There are a large number of studies that have reported a similar lack of association of various CYP genetic variants with OSCC, as reviewed by Vukovic and colleagues (25) and Qiu and colleagues in excellent meta-analyses (26). However, this was the rst study attempting to nd out the association of CYP2C9 genetic polymorphisms with OSCC.…”

Immobilization stress increased cytochrome P450 1A2 (CYP1A2) expression in the ovary of rat

“…The studies of CYP1A2 expression are mainly focused on the liver to understand its role with respect to biotransformation and metabolism of exogenous substances and endogenous hormones (Mikhailova et al, 2006;Sugiyama et al, 2019). In the recent days, CYP1A2 expression in the other tissues including the pancreas, lung and ovary has been investigated (Vukovic et al, 2016;Hwang et al, 2020). Especially, there have been several articles identified that the expression of CYP family in the ovary is affected by several internal or external factors.…”

“…It has been known that CYP1A2 is mainly expressed in the liver to metabolize the aromatic amines and heterocyclic compounds of exogenous substances and endogenous hormones (Mikhailova et al, 2006;Sugiyama et al, 2019;Lu et al, 2020). However, in the recent days, it has been verified that CYP1A2 is also expressed in various organs in terms of the pancreas, lung and ovary (Hong et al, 2004;Vukovic et al, 2016;Hwang et al, 2020). Especially, it is found that expression of CYP isoforms in the ovary can be altered under 3-methylcholanthrene (3MC; Ah receptor ligand) treatment, the onset of puberty, methoxychlor (MXC; estrogenic endocrine disruptor) application (Dey et al, 1999;Symonds et al, 2006;Hwang et al, 2020).…”