Four Polymorphisms in the Cytochrome P450 1A2 (CYP1A2) Gene and Lung Cancer Risk: a Meta-analysis

Abstract

Background: Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526, and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present metaanalysis of the literature was performed to derive a more precise estimation of the relationship. Materials and Methods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383 controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7 studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls for CYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysis for the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominant model (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lung cancer was observed in Caucasians (dominant model: OR=1.29, 95%CI=1.11-1.51; recessive model: OR=1.33, 95%CI=1.01-1.75; additive model: OR=1.49, 95%CI=1.12-1.98). There was no evidence of significant association between lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: In summary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lung cancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514 associations in lung cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the rs2069514 polymorphism in lung cancer development.

The associations of genetic polymorphisms inCYP1A2andCYP3A4with clinical outcomes of breast cancer patients in northern China

“…Chen et al [28] found that the allele C was associated with increased hepatocellular carcinoma (HCC) susceptibility in Chinese population, in HBsAg seronegative individuals, and in heavy smokers. A meta-analysis showed no evidence of significant associations between CYP1A2 rs2470890 and lung cancer risk among Caucasian and Latinos [14]. However, thus far, there has been no evidence involving the role of CYP1A2 rs2470890 played in breast cancer.…”

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

“…To the best of our knowledge, this is the largest and most comprehensive meta-analysis on CYP1A2 SNPs and cancer performed so far. Several previous meta-analyses have been reported on the association between CYP1A2 gene polymorphisms and risk of cancer [ 86 – 95 ]. Deng et al [ 87 ] reported no association between CYP1A2 rs762551 polymorphism and lung cancer risk by including 1675 cases and 2393 controls.…”

“…In one recent meta-analysis by Zhi-Bin Bu et al [ 86 ] on the association between CYP1A2 rs762551, rs2069514, rs2069526, and rs2470890 polymorphisms and lung cancer risk, there was no evidence of significant association between lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. They found increased lung cancer risk for rs762551 polymorphism in Caucasians from 3 studies, while in our analysis there was no such connection on a bigger sample of studies [ 24 , 26 – 28 , 30 – 32 ].…”

The Roles of microRNAs in Cancer Multidrug Resistance

“…CYP1A2 is one of the most important enzymes involved in drug metabolism; its expression in the liver reaches 13–15% of all CYPs [ 106 ], and it is metabolized by approximately 9% of currently prescribed drugs [ 107 ]. Several polymorphisms of the CYP1A2 gene are associated with an increase in its drug-metabolizing activity and a worsening of the prognosis of, for example, lung cancer [ 108 , 109 ]. Its expression is effectively reduced by miRNA-132-5p CYP1A2 in hepatocytes, and this reduction is alleviated by lansoprazole-enhanced hepatotoxicity induced by flutamide [ 110 ].…”