The different results regarding the genetic effect of GSTM3 intron 6 A/B polymorphism on the risk of cancer were reported by individual researchers. For example, GSTM3 A/B polymorphism seems not to be linked to the risk of oral cancer in the African-American population , but not in the Indian population . In the present study, we searched the available case-control studies for the comprehensive assessment of the role of GSTM3 A/B polymorphism in the overall cancer.
Even though no meta-analysis of overall cancer and GSTM3 intron 6 A/B polymorphism were reported, there are several meta-analyses regarding the association between GSTM3 A/B polymorphism and specific cancer type, including head and neck cancer , lung cancer [4, 67], and osteosarcoma . In 2006, Ye, Z. enrolled a total of five case-control studies for a meta-analysis of head and neck cancer, reported the no significant overall association between GSTM3 A/B polymorphism and lung cancer risk . In 2012, Feng, X. performed an updated meta-analysis with eight case-control studies, and the similar negative result was detected . For the meta-analysis of osteosarcoma , only two case-control studies were included. In 2014, Xu, Y. conducted the meta-analysis of head and neck cancer with 14 case-control studies, and reported that GSTM3 A/B polymorphism seems to be linked the decreased risk of head and neck cancer. In the present study, a total of fifty-eight case-control studies (17,125 cases / 22,342 controls) from the fifty-three articles were enrolled. And the six genetic models, including the allelic B vs. A, BB vs. AA, AB vs. AA, AB + BB vs. AA, BB vs. AA + AB, carrier B vs. A, were applied. However, no positive genetic association between GSTM3 intron 6 A/B polymorphism and the risk of overall cancer was detected. We then performed the subgroup meta-analysis, based on the factors of ethnicity, control source, HWE and cancer type. The subgroup analysis of “brain cancer”, “head and neck cancer”, “lung cancer”, “skin cancer”, “urinary system cancer”, “breast cancer”, “digestive system cancer”, “oral cancer”, “glioma” and “colorectal cancer” were conducted. Our data suggested the potential association between BB genotype of GSTM3 and the decreased risk of head and neck cancer. Furthermore, we focused on the specific SCC or BCC type of cancer and performed the meta-analysis of “head and neck SCC”, “skin SCC”, or “skin BCC”. Our data supported the protective role of GSTM3 intron 6 A/B polymorphism on the risk of head and neck SCC cancer.
Our meta-analysis exhibits several advantages. First, more than fifty case-control studies were enrolled for our comprehensive assessment. Second, our results of Begg’s and Egger’s tests ruled out the presence of large publication bias. Third, our sensitivity analyses support the stability of pooling results.
Despite this, some disadvantages still may limit our statistical evaluation. First, as in other meta-analyses, a small sample size was enrolled in some subgroup analyses. For example, only three case-control studies were included in the subgroup meta-analysis of “breast cancer”, “glioma”, “colorectal cancer”, and “skin SCC”. Even though the positive result was observed in the subgroup analysis of “head and neck SCC”, no more than ten case-control studies were included. Moreover, due to the lack of enough genotypic data, we did not perform the subgroup of specific head and neck SCC in the Asian or Caucasian population. Second, a high heterogeneity level among studies was observed in the allelic, heterozygotic or dominant meta-analyses. Third, the genotypic distribution of control groups in some studies was not in line with the Hardy-Weinberg equilibrium. Fourth, of the eligible case-control studies, only the combined “AB + BB” genotypic frequency data were extracted in some studies [18, 20, 25, 31, 35, 44, 50, 58]. Fifth, in this study, we only study the GSTM3 intron 6 A/B polymorphism. And the role of other polymorphisms within GSTM3 gene in the risk of cancer, such as rs1055259, rs3814309, or 5776997, or the combined genetic effect of GSTM3 gene and other GST genes, such as GSTM1, GSTP1, GSTT1, should be investigated, when the enough genotypic data was available. Moreover, the additional adjusted clinical or environmental factors should be conducted when we can obtain access to more association investigation data for years to come.