In randomly selected human genomes, approximately 0.1% of the gene sequences are different. The cause of this change is a genetic mutation called polymorphism. There is no doubt that the identification of genes underlying polygenic and complex diseases can be used by clinicians and geneticists for the diagnosis and treatment of disease, evolutionary biology studies, and gene discovery and mapping[30].
SNPs are relatively stable and not affected by disease activity and remain unchanged over time. For analyzing complex diseases such as cancer, biogenetic research is a powerful method of determining low-penetrance susceptibility genes that can affect biological processes, which can be used for linkage analysis[31].
Inflammatory response plays an important role in host response against infection and participates in tissue repair, in case of damage. Chronic inflammation causes repeated tissue damage and repair, which alters the immune system and ultimately leads to cancer[32]. In recent years, cytokines are receiving increasing attention due to their function in adjusting and balancing the immune response including inflammation. They can also regulate the pro-inflammatory and anti-inflammatory network and participate in tissue damage and repair to stimulate signaling pathways involved in malignancy development[33]. In 1982, IL-16 was initially identified as a T cell chemoattractant factor produced from mitogen- or antigen-stimulated human peripheral blood mononuclear cells [34]. As a cytokine, IL-16 participates in various cellular biological processes, including the chemotaxis of immune cells, initiation of inflammatory responses, and production of proangiogenic cytokines [35]. Therefore, it may be involved in the occurrence and development of cancer.
Many scientists have reported the association between IL-16 rs4778889 T > C gene polymorphism and cancer risk. However, the results are contradictory. In addition, the molecular and biological mechanism behind the association between IL-16 rs4778889 T > C gene polymorphism and cancer risk is not completely understood. Therefore, a larger sample size and subgroup analysis are needed to evaluate the potential role of IL-16 rs4778889 T > C polymorphism as a genetic risk factor for cancer. A large sample size with statistical robustness can decrease random errors by combining ORs from many early published researches[36]. Meta-analyses address a wide variety of clinical problems using early published data. The present meta-analysis included 12 case–control studies with 3066 cases and 4433 controls and analyzed the pooled ORs and P-value to determine the precise relationship between IL-16 rs4778889 T > C gene polymorphism and cancer risk. The results showed no association between the IL-16 rs4778889 T > C gene polymorphism and cancer susceptibility by any genetic model. At the same time, the results of subgroup analysis showed that the IL-16 rs4778889 T > C gene polymorphism was not associated with renal cell carcinoma, digestive cancer, and nasopharyngeal carcinoma.
An early meta-analysis by Xu et al.[11] did not find any association between the IL-16 rs4778889 T > C polymorphism and cancer. Generally, this meta-analysis yielded the same results, making our study redundant. However, the present study has the following advantages: first, this meta-analysis added new published studies that increased the number of included subjects in both cases and controls. A total of 12 studies were analyzed, which was more representative of rs4778889 than the previous meta-analysis. Hence, our results provide strong evidence to draw accurate and robust conclusions that make our results more credible. Second, the subgroup analyses were performed in accordance with the type of cancer (renal cell carcinoma, digestive cancer, nasopharyngeal carcinoma) to explore the possible sources of heterogeneity, measure the stability of studies, and investigate the role of IL-16 in the pathogenesis of different cancers. Therefore, to a certain extent, our meta-analysis provides a more precise result that the IL-16 rs4778889 T > C gene polymorphism is not significantly associated with cancer risk.
Although case-control studies were included, the results of the current meta-analysis should be interpreted carefully due to the following limitations. First, interstudy heterogeneity was discovered in the overall comparison from each genetic model, which may be due to differences in countries, ethnicities, and sources of controls. Therefore, we minimized the likelihood of this problem by performing data analysis using the random-effects model. Second, the study included only Asian populations. The results may require further verified in multiple ethnic groups. Third, the occurrence of cancer is the result of multiple factors. Gene and environment interactions may play important roles in the pathology of cancer. We did not analyze gene and environment interactions and epigenetic inheritance. Other risk factors, including age, ethnic groups, body mass index, and smoking and drinking status, are also associated with the occurrence of cancer.