谷胱甘肽S-转移酶M1、T1、P1基因多态性与膀胱癌易感性的关联

Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer.

作者信息

Srivastava Daya Shankar Lal, Mishra Dhruva Kumar, Mandhani Anil, Mittal Balraj, Kumar Anant, Mittal Rama Devi

机构信息

Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow-226014, Uttar Pradesh, India.

出版信息

Eur Urol. 2005 Aug;48(2):339-44. doi: 10.1016/j.eururo.2005.02.007. Epub 2005 Mar 7.

DOI:10.1016/j.eururo.2005.02.007

PMID:16005379

Abstract

OBJECTIVE

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. We examined the association of the GST gene polymorphism with sporadic bladder cancer patients in Northern India.

MATERIAL AND METHODS

The study constituted of 106 bladder cancer cases and 370 age-matched controls. The GSTT1 and GSTM1 null genotypes were identified by multiplex PCR and GSTP1313 A/G by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism method (PCR/RFLP).

RESULTS

We observed non-significant association in null alleles of the GSTM1 (p = 0.611, OR = 1.12, 95% CI = 0.72-1.74 and GSTT1 (p = 0.135, OR = 1.45, 95% CI = 0.89-2.37) with risk of bladder cancer. However, the G/G genotype of the GSTP1 gene polymorphism was highly significant when compared to controls (p=0.000, OR = 7.12, 95% CI = 3.14-16.16). The combined analysis of the three risk genotypes demonstrated further increase in the risk of bladder cancer (p = 0.000, OR = 7.29 95% CI = 2.81-18.93).

CONCLUSION

Our study demonstrated that GSTP1313 G/G polymorphism is a strong predisposing risk factor for bladder cancer. Combination of three GST genotypes association exhibiting gene-gene interaction further substantiates the increased risk of bladder cancer.

摘要

目的

谷胱甘肽-S-转移酶（GSTs）在多种内源性或外源性致癌物的解毒过程中发挥作用。我们研究了印度北部散发性膀胱癌患者与GST基因多态性之间的关联。

材料与方法

该研究纳入了106例膀胱癌患者和370例年龄匹配的对照。通过多重PCR鉴定GSTT1和GSTM1无效基因型，采用聚合酶链反应/限制性片段长度多态性方法（PCR/RFLP）鉴定GSTP1 313A/G。

结果

我们观察到GSTM1无效等位基因（p = 0.611，OR = 1.12，95%CI = 0.72 - 1.74）和GSTT1无效等位基因（p = 0.135，OR = 1.45，95%CI = 0.89 - 2.37）与膀胱癌风险之间无显著关联。然而，与对照组相比，GSTP1基因多态性的G/G基因型具有高度显著性（p = 0.000，OR = 7.12，95%CI = 3.14 - 16.16）。三种风险基因型的联合分析显示膀胱癌风险进一步增加（p = 0.000，OR = 7.29，95%CI = 2.81 - 18.93）。