Association of Promoter Region Polymorphisms of IL-10 Gene with Susceptibility to Lung Cancer: Systematic Review and Meta-Analysis

Abstract

Objective:Epidemiological studies have suggested that the promoter region polymorphisms of interleukin-10 (IL-10) gene may be associated with an increased risk of lung cancer. However, those studies results are controversial. Thus, a comprehensive meta-analysis was performed to evaluate the association of promoter region polymorphisms of IL-10 gene with susceptibility to lung cancer. Methods:a comprehensive search of PubMed, EMBASE, and CNKI databases was performed to find all eligible studies up to September 15, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. Results:A total number of 19 case-control studies with 4084 cases and 6,131 controls were selected. The overall meta-analysis results showed that the -592A>C polymorphism was significantly associated with lung cancer risk under four genetic models, i.e., allele (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02), homozygote (CC vs. AA: OR= 1.64, 95% CI 1.29-2.02, p≤0.001), heterozygote (CA vs. AA: OR= 1.26, 95% CI 1.06-1.50, p≤0.001), and dominant (CC+CA vs. AA: OR= 1.31, 95% CI 1.11-1.54, p=0.001). However, there was no significant association between -819T>C and -1082A>G polymorphisms of IL-10 and lung cancer risk. Similarly, subgroup analyses by ethnicity detected significant association between IL-10 -592A>C and lung cancer among Asians and Caucasians. Conclusions:Our meta-analysis suggests that the IL-10 -592A>C polymorphism might be risk factor for lung cancer, especially among Asian and Caucasians. In contrast, the IL-10 -819T>C and -1082A>G polymorphisms are not significantly associated with increased risk of lung cancer.

IL10 as Cancer Biomarker

“…Another meta-analysis suggests that the polymorphism associated with a risk factor for lung cancer was IL10 −592A > C polymorphism, especially among Asians and Caucasians. In contrast, the IL10 −819 T > C and −1082A > G polymorphisms are not significantly associated with an increased risk of lung cancer [87].…”

Association of IL-10-1082G > A, -819C > T and -592C > A Polymorphisms with susceptibility to asthma in children: a Systematic Review and Meta-Analysis

“…The IL-10 promoter is highly polymorphic [17][18][19][20], and three single nucleotide polymorphisms (SNPs) at positions -1082G>A, -819C>T and -592C>A polymorphisms within the promoter region have been shown to correlate with IL-10 production (22,24,25). To date, several genetic epidemiology studies have assessed the association between IL-10 -1082G>A, -819C>T and -592C>A polymorphisms and pediatric asthma in different populations (26,27).…”

“…Human IL-10 has a broad-spectrum antiinflammatory activity which is expressed by activated monocytes/macrophages, natural killer (NK) cells, dendritic cells (DCs), mast cells, B cells, and regulatory T cell subsets (16). Moreover, IL-10 is known to have macrophage-deactivating properties and undermines the Th1-driven pro-inflammatory response by down-regulating the production of several cytokines (17,18). Human IL-10 gene maps to chromosome 1q31-32, contains four introns and five exons, and spans about 4.7 kb (19).…”

Cytokine-based Cancer Immunotherapy: Challenges and Opportunities for IL-10

“…Yet, metaanalyses are conflicting on IL-10 rs1800896 and rs1800871 polymorphisms and breast cancer susceptibility (38,48,49). Equally, studies across prostate (50)(51)(52), skin (53,54), lung (55), gastric (56) and cervical cancers (57,58) have not been consistent.…”