The alterations of apoptosis-related genes are probably contributing to malignant tumors, including cervical cancer . Fas is an important apoptosis-related gene and known as a member of tumor necrosis factor (TNF) receptors superfamily . Downregulation of Fas with resultant resistance to death signals has been reported in many cancers . Furthermore, the transcript expression of Fas is modulated by genetic elements which located in the 5′ upstream promoter region of the gene. SNP at -670 in the enhancer region (A/G) locates at a binding element of gamma interferon activation signal (GAS). Homozygous for G allele (GG) could lead to a complete deletion of the binding sequence of transcription element GAS, which is responsible for the signal emanated through STAT1, and in a significant alteration in the gene expression .
Although previous meta-analysis maybe involves some parts of the relationship between Fas rs180082 polymorphism and cervical cancer risk, its eligible studies are not quite comprehensive . First, lack of the population of African, which leads to the decrease of studies and may cause a deviation to final result; second, some of the its eligible studies regard squamous cell carcinoma (SCC) or squamous intraepithelial lesion (SIL) as the cervical cancer [29, 33]. However, SCC is just one pathological type of cervical cancer and SIL is just a stage in the pathological process of cervical cancer, which may also bring some bias. Therefore, we conduct an update by meta-analysis to comprehensively evaluate the association between rs180082 polymorphism and cervical cancer risk. This update meta-analysis includes seven latest case–control studies, five of which are published in recent 5 years. Despite the number of eligible studies in this meta-analysis is still infinite, all the studies included in this meta-analysis, which are based on stricter search criteria, are more reliable and lead to a more accurate result.
As for cervical cancer risk, the previous results of the studies involving Fas rs180082 polymorphism were contradictory. These inconsistent results were possibly due to small effect of the polymorphism on cervical cancer risk or the relatively low statistical power of the published studies. Consequently, the meta-analysis was needed to provide a quantitative approach for combining the results of various studies with the same topic and for estimating and explaining their diversity.
So far, the number of the studies that focus on the relationship between Fas rs180082 polymorphism and cancer risk is limited. Some studies before had shown that there was an association between Fas rs180082 and some cancers, including nasopharyngeal carcinoma , lung cancer [37, 38], gastric cancer  and leukemia . Otherwise, some studies draw a different conclusion .
The studies included in our meta-analysis may differ in some aspects. Koushik, et al. conducted the first African population study with 447 women with invasive cervical cancer and 424 healthy women controls . Li, et al. conducted the study with 314 women of cervical cancer and 615 healthy women controls in South China . Kordi, et al. conducted the first study in North India . Zoodsma, et al. and Kang, et al. conducted the same study in Netherland and South Korea [14, 15]. All of them did not find any significant association between Fas rs180082 polymorphism and cervical cancer susceptibility. However, Ueda, et al. found that polymorphism of Fas gene promoter -670 may be associated with the risk of cervical cancer in a Japanese population. It should be pointed out that the study which focused on Japanese population is based on small sample size (<200 subjects), so that we should be cautious to the result of this study. Consequently, our data failed to find a relationship between Fas rs180082 polymorphism and cervical cancer risk. The present meta-analysis, which included 1856 cases of cervical cancer and 2097 controls, suggested that there was no association between Fas rs180082 polymorphism and cervical cancer susceptibility.
Considering the results may be due to different ethnicity, we further conducted subgroup analysis according to ethnicity. When stratifying for ethnicity, significant association was detected in neither Asian populations nor African populations, suggesting that the genetic background or environment they live in may not influence the Fas rs180082 polymorphism on cervical cancer susceptibility. However, the conclusion should be cautious. Because the sample size of studies included in our meta-analysis is relatively small, especially in the African population. Our results may be underpowered so that further studies need to be conducted to increase the statistical power. The genetic distance between different ethnicities considered together could be substantial. It is not excluded that true effects are present in one specific sub-population, but undetected due to lack of statistical power or diluted/cancelled out by population stratification issues when different study populations are grouped together for analysis.
Some limitations of this meta-analysis we need to pay attention to. First, our results are based on unadjusted estimates and a more precise analysis stratified by age, different lifestyle related habits and different grades of cervical cancer could be performed if individual data were available. Second, lack of the original data of the reviewed studies limited our precise estimation of the relation, which might cause some bias. Third, the lack of original study limited our further evaluation of potential interactions because the interactions between gene-environment interactions may modulate cancer risk.
Despite these limitations or disadvantages, our meta-analysis still had some advantages. First, a systematic review of the association of Fas rs180082 polymorphism with cervical cancer risk is statistically more powerful than any single study. Second, the studies retrieved were the latest, half of which were published in the recent 3 years. Third, the quality of case–control studies included in our Meta analysis was satisfactory and met our inclusion criteria.