It is well recognized that there is a range of individual susceptibility to the same kind of cancer even with identical environmental exposure. Host factors, including polymorphisms of genes involved in carcinogenesis, may have accounted for this difference. Therefore, genetic susceptibility to cancer has been a research focus in scientific community.
This meta-analysis, including 4,828 cancer cases and 4,890 controls from 12 published case–control studies, explored the association between the XPC Lys939Gln polymorphism and bladder cancer risk. Overall, we found that there was evidence that the variant genotypes of the XPC Lys939Gln were associated with a significant increased overall risk of bladder cancer. In the subgroup analysis based on ethnicities, significant associations were found between both African and Asian populations for some genetic models, suggesting that XPD Lys939Gln polymorphism play similar roles in populations with different genetic backgrounds and living environment. Simultaneously, our results also showed that significantly increased bladder cancer risk in homozygous, heterozygous, recessive and allele comparison models were noted in the population-based studies but not in hospital-based studies.
There are some limitations should be acknowledged in this meta-analysis. Firstly, bladder cancer is a multi-factorial disease that results from complex interactions between many genetic and environmental factors. It suggests that there will not be single gene or single environmental factor that has large effects on bladder cancer susceptibility. Secondly, in the subgroup analyses by ethnicity and source of controls, the number of subjects was relatively small, not having enough statistical power to explore the real association. Thirdly, the controls were not uniformly defined. Although most of the controls were selected mainly from healthy populations, some had respiratory disease. Therefore, non-differential mis-classification bias was possible because these studies may have included the control groups who had different risks of developing bladder cancer. Fourth, our meta-analysis is similarly with other works[20–22], while a more precise analysis should be conducted if individual data were available, which would allow for the adjustment by other covariates including age, sex, family history, environmental factors and lifestyle. Furthermore, other pathological type of urinary bladder cancer should be considered [23–25], which may be the source of publication. In addition, as in most meta-analyses, publication bias must be considered because only published studies were included in the meta-analysis.
Despite some limitations listed above, our meta-analysis had several advantages. First, sufficient number of cases and controls were pooled from different studies, which significantly increased the statistical power of the analysis. Second, no publication biases were detected, indicating that there is no bias among the pooled results.