Association between cytochrome P450 1A1 (CYP1A1) gene polymorphisms and the risk of renal cell carcinoma: a meta-analysis.

Fan-Dong Meng,You-Hong Jiang,Ping Ma,Xin Tian,Cheng-Guang Sui

doi:10.1038/srep08108

Fan-Dong Meng, You-Hong Jiang + Show 3 more

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https://doi.org/10.1038/srep08108

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Abstract

Cytochrome P450 1A1 (CYP1A1) usually metabolizes carcinogens to their inactive derivatives but occasionally converts the chemicals to more potent carcinogens. To date, many studies have evaluated the association between the CYP1A1 MspI and Ile462Val polymorphisms and renal cell carcinoma (RCC) risk, but the results have been conflicting. To more precisely evaluate the potential association, we carried out a meta-analysis of seven published case-control studies. The meta-analysis indicated that the MspI polymorphism was associated with an increased RCC risk (allele model: OR = 1.49, 95%CI 1.03–2.16; homozygous model: OR = 1.64, 95%CI 1.13–2.40; dominant model: OR = 1.72, 95%CI 1.07–2.76). No significant associations were found for the Ile462Val polymorphism for all genetic models. When stratified by smoking status, smokers carrying the variant Vt and Val allele were more susceptible to RCC (Vt allele: OR = 3.37, 95%CI = 2.24–5.06; Val allele: OR = 2.07, 95%CI = 1.34–3.19). These data indicate that the CYP1A1 MspI polymorphism significantly increased RCC risk, while the Ile462Val polymorphism was not associated with RCC. Among smokers, individuals with the CYP1A1 Vt allele and Val allele showed a significantly increased risk of RCC. More well-designed studies with larger samples are warranted to show the underlying mechanisms of CYP1A1 in the development of RCC.

Highlights

Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shenyang 110001, China
Polymorphisms of the Cytochrome P450 1A1 (CYP1A1) enzymes may contribute to the variable susceptibility to carcinogenesis by altering the level of gene expression or messenger RNA stability, resulting in highly inducible activity of the enzyme
To the best of our knowledge, this is the first meta-analysis to assess the association between the CYP1A1 MspI and Ile462Val polymorphisms and renal cell carcinoma (RCC) risk

Summary

Introduction

When stratified by smoking status, smokers carrying the variant Vt and Val allele were more susceptible to RCC (Vt allele: OR 5 3.37, 95%CI 5 2.24–5.06; Val allele: OR 5 2.07, 95%CI 5 1.34–3.19) These data indicate that the CYP1A1 MspI polymorphism significantly increased RCC risk, while the Ile462Val polymorphism was not associated with RCC. Two functional nonsynonymous polymorphisms in the CYP1A1 gene have been recently studied: a thymine (T) to cytosine (C) transition in the noncoding 39-flanking region (MspI, rs4646903), and an adenine (A) to guanine (G) substitution at codon 462 in exon 7 (Ile462Val, rs1048943)[6] These variations could alter CYP1A1 expression and function, potentially influencing the balance between metabolic activation and detoxification of toxicants, and leading to individual susceptibilities to cancer[7]. We performed a meta-analysis of all currently available publications to examine whether the genotype status of the two polymorphisms in CYP1A1 is associated with RCC risk

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