Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, Po Box 1177, 3018, Sfax, Tunisia.
Unit of Marine and Environmental Toxicology, UR 09-03, Sfax University, IPEIS, BP 1172, 3018, Sfax, Tunisia.
Environ Sci Pollut Res Int. 2017 Oct;24(28):22476-22484. doi: 10.1007/s11356-017-9767-x. Epub 2017 Aug 12.
Other than the established environmental risk factors associated with bladder cancer (BC), little is known about the genetic variations determining the individual susceptibility of this complex disease. This study aimed to investigate the relationship of BC with environmental agents and polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes and CYP1A1, CYP2D6, NAT1, and NAT2 xenobiotic metabolism genes through a hospital-based case-control study in Tunisia. The selection of the single nucleotide polymorphisms (SNPs) (rs25487, rs 13181, rs415407, rs446421, rs1058172, rs4921880, and rs1208) was performed using the dbSNP database. DNA genotyping was determined by PCR-RFLP after DNA extraction from whole blood. The risks of BC associated with every polymorphism as well as the studied environmental factors were estimated by multivariate-adjusted logistic regression using R software. In addition, gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. Results showed that tobacco smoking and chewing parameters were significantly associated with BC risk. Single-gene variant analysis showed significant associations of the TT genotype of CYP1A1 and the rare GG genotype of ERCC2 with bladder cancer susceptibility (OR = 1.34, 95% CI 1.22-1.40, P < 0.0001). According to GMDR analysis, our findings indicated a significant association between BC and gene-gene interaction among the CYP1A1, ERCC3, and XRCC1. The present results suggest a potential role of XRCC1, ERCC2, ERCC3, and CYP1A1 besides tobacco intake in susceptibility to BC.
除了与膀胱癌 (BC) 相关的已确定的环境风险因素外，对于决定这种复杂疾病个体易感性的遗传变异知之甚少。本研究旨在通过突尼斯的一项基于医院的病例对照研究，调查 BC 与环境因素以及 XRCC1、ERCC2 和 ERCC3 DNA 修复基因和 CYP1A1、CYP2D6、NAT1 和 NAT2 外源物代谢基因中的多态性之间的关系。单核苷酸多态性 (SNP) (rs25487、rs13181、rs415407、rs446421、rs1058172、rs4921880 和 rs1208) 的选择是使用 dbSNP 数据库进行的。从全血中提取 DNA 后，通过 PCR-RFLP 确定 DNA 基因分型。使用 R 软件通过多变量调整逻辑回归估计与每个多态性以及研究的环境因素相关的 BC 风险。此外，使用广义多因素降维 (GMDR) 方法分析基因-基因相互作用。结果表明，吸烟和咀嚼参数与 BC 风险显著相关。单基因变异分析显示 CYP1A1 的 TT 基因型和 ERCC2 的罕见 GG 基因型与膀胱癌易感性显著相关 (OR=1.34,95%CI1.22-1.40, P<0.0001)。根据 GMDR 分析，我们的研究结果表明，BC 与 CYP1A1、ERCC3 和 XRCC1 之间的基因-基因相互作用之间存在显著关联。目前的结果表明，除了吸烟之外，XRCC1、ERCC2、ERCC3 和 CYP1A1 可能在 BC 的易感性中起作用。
