Lei Zeyuan, Liu Ting, Li Xiang, Xu Xiaoxia, Fan Dongli
Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, The Third Military Medical University Chongqing 400037, China.
Int J Clin Exp Med. 2015 Jan 15;8(1):377-86. eCollection 2015.
Glutathione S-transferase (GST) family genes are of vital importance in maintaining cellular defence systems, protecting cells against the toxic effects of reactive oxygen produced during the synthesis of melanin, and detoxifying environmental mutagens and chemical or synthetic drugs. As no previous meta-analyses have examined the association of polymorphisms at GSTT1, GSTP1 Ile105Val with skin cancer risk and independently published studies have produced inconsistent conclusions, we were promoted to estimate the associations in the largest study to date.
Computer-assisted searches were carried out to systematically identify the studies of GST polymorphisms and skin cancer. The eligibility of studies was evaluated following the requirements of inclusion criteria. Risk of skin cancers (OR and 95% CI) was assessed with the fixed or random effects meta-analysis.
The fixed effects meta-analysis of 15 studies suggested no overall association between GSTT1 null and skin cancer. Nor was there a significant association in any subgroup. However, in the stratified analysis by histologic type for GSTP1 Ile105Val, we found 1.56 times higher risk of malignant melanoma (MM) among people with the 105-Val/Val genotype (Val/Val vs. Ile/Ile: OR = 1.56, 95% CI = 1.05-2.32, pheterogeneity = 0.584).
These statistical data demonstrate that Ile105Val polymorphism of the GSTP1 gene may have genetic contribution to the development of skin cancer, MM in particular.
谷胱甘肽S-转移酶(GST)家族基因在维持细胞防御系统、保护细胞免受黑色素合成过程中产生的活性氧的毒性作用以及使环境诱变剂和化学或合成药物解毒方面至关重要。由于此前尚无荟萃分析研究GSTT1、GSTP1 Ile105Val基因多态性与皮肤癌风险的关联,且独立发表的研究得出了不一致的结论,因此我们开展了迄今为止规模最大的研究来评估这些关联。
通过计算机辅助检索系统地识别GST基因多态性与皮肤癌的研究。根据纳入标准的要求评估研究的合格性。采用固定效应或随机效应荟萃分析评估皮肤癌的风险(比值比及95%置信区间)。
对15项研究的固定效应荟萃分析表明,GSTT1基因缺失与皮肤癌之间无总体关联。在任何亚组中也无显著关联。然而,在按组织学类型对GSTP1 Ile105Val进行的分层分析中,我们发现105-Val/Val基因型个体患恶性黑色素瘤(MM)的风险高1.56倍(Val/Val与Ile/Ile相比:比值比 = 1.56,95%置信区间 = 1.05 - 2.32,异质性p = 0.584)。
这些统计数据表明,GSTP1基因的Ile105Val多态性可能对皮肤癌尤其是MM的发生有遗传贡献。