Abstract
Background and ObjectivesGlutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens.MethodsIn this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable.ResultsThe null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51).ConclusionThese findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.
Highlights
Cervical cancer is the second most frequent cancer among women worldwide, with approximately 493,000 new cases diagnosed and 274,000 deaths occurring each year (2002 estimates) [1]
Selection of Published Studies We identified all publications by conducting computer-based searches of PubMed, EMBASE, ISI Web of Science, and CBM databases without language restrictions, using the following search algorithm: (‘‘cervical cancer’’ or ‘‘cervical carcinoma’’ or ‘‘uterine cervix cancer’’ or ‘‘CC’’ or ‘‘cervical neoplasia’’) and (‘‘glutathione S-transferase’’ or ‘‘Glutathione S-transferases (GSTs)’’ or ‘‘GSTM’’ or ‘‘GSTM1’’ or ‘‘GSTT’’ or ‘‘GSTT1’’) and (‘‘polymorphism’’ or ‘‘polymorphisms’’ or ‘‘variant’’)
Of the 25 studies, 23 studies investigated the association between GSTM1 polymorphism and risk of cervical neoplasia and 19 studies investigated the association between GSTT1 polymorphism and risk of cervical neoplasia
Summary
Cervical cancer is the second most frequent cancer among women worldwide, with approximately 493,000 new cases diagnosed and 274,000 deaths occurring each year (2002 estimates) [1]. The burden of cervical cancer is the high incidence rates in women in some developing countries, and the societal impact because a fraction of patients who suffered from the disease in their 30’s or 40’s are still raising or supporting families. Many research efforts were taken to identify cofactors for cervical cancer development. The familial relative risk for individuals with biological full-sisters of cervical cancer cases is almost twice as high as those with biological full-sisters of controls [11,12,13]. Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens
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