Meta-analysis of the Correlation Between Interleukin-6 Promoter Polymorphism -174G/C and Interferon Regulatory Factor 4 rs12203592 Polymorphism With Skin Cancer Susceptibility

Abstract

Inflammation is a process whereby the immune system responds to a disease or injury. Chronic inflammation, however, has been linked to several types of cancers such as skin cancer. Molecular epidemiological studies were carried out in recent years evaluating interferon regulatory factor 4 (IRF4) rs12203592 and interleukin-6 (IL-6) gene -174G/C polymorphism associated with skin cancer risk for different groups of people. However, the results are still conflicting, not conclusive. We performed a meta-analysis to investigate the association between cancer susceptibility and IL-6 -174G/C (1130 cases and 1260 controls from 7 studies) and IRF4 rs12203592 polymorphisms (3879 cases and 6759 controls from 9 studies) in different inheritance models. We assess the strength of association of odds ratio (ORs), 95% confidence interval (CI). Overall, significantly elevated skin cancer risk was found when all studies were pooled into the meta-analysis of IL-6 -174G/C (For GC vs. GG: OR = 1.28, 95% CI, 1.06-1.54, I = 0, Pheterogeneity = 0.816; for CC/GC vs. GG: OR = 1.26, 95% CI, 1.05-1.50, I = 0, Pheterogeneity = 0.618). However, for IRF4 rs12203592 polymorphism, significantly increased risk of skin cancer was observed in TT versus CC (OR = 1.99, 95% CI, 1.30-3.07, I = 76.7%, Pheterogeneity < 0.001) and in recessive model (OR = 1.91, 95% CI, 1.31-2.77, I = 69.9%, Pheterogeneity < 0.001). This meta-analysis indicates that the IL-6 gene -174G/C and IRF4 rs12203592 polymorphisms may be associated with an increased skin cancer risk.

Association between single nucleotide polymorphisms of IL-6 and susceptibility to skin cancer: a meta-analysis and systematic review

“…Overall, we found that the risk of skin cancer was not related with both IL - 6 gene polymorphisms. The earlier meta-analysis by Wu et al found the IL - 6 gene 174G/C might be associated with increased skin cancer risk ( 15 ), which is contradictory as compared with ours. We considered that the reasons for the different results may be due to the newly published studies.…”

“…However, due to the limited research included in our study, this conclusion still needs to be confirmed by future research. In conclusion, none of the subgroups showed meaningful results except the subgroup of publication year before 2010 (GC + CC vs. GG: OR =1.255, P=0.012; GC vs. GG: OR =1.277, P=0.01), which is consistent with the previous meta-analysis by Wu et al (15). On the contrary, there is no statistical significance in the other subgroup of publication year after 2010 (P>0.05 for all genotypes).…”

“…On the contrary, Wang et al discovered that the G allele in rs1800795-174 might enhance the susceptibility to BCC (G vs. C: OR =1.38, P=0.012) ( 14 ). Five years earlier, a meta-analysis by Wu et al summarized and analyzed the association between IL-6 polymorphism and skin cancer, and found that rs1800795-174G/C was associated with the risk of skin cancer (for GC vs. GG: OR =1.28, P=0.816; for CC/GC vs. GG: OR =1.26, P=0.618) ( 15 ). However, the data in the meta-analysis by Wang et al could not draw a definite conclusion, and the included literatures were 10 years ago.…”

Susceptibility Loci-Associated Cutaneous Squamous Cell Carcinoma Invasiveness

“…We report three other SNPs that are associated with an invasive cSCC tumor phenotype. The minor T risk allele at rs12203592 in IRF4 has been shown to modulate an enhancer element that controls IRF4 expression (Visser et al, 2015) and has been previously shown to be associated with increased skin cancer susceptibility (Wu et al, 2016). IRF4 is associated with immune system development and response, and its transcription status in the epidermis is strongly correlated with the allelic status of rs12203592 (Visser et al, 2015).…”

IRF4 Polymorphism Is Associated with Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients: A Pigment-Independent Phenomenon

“…In a recent meta-analysis, the association between rs12203592 polymorphism and SCC was significant in dominant, recessive, and codominant models (Wu et al, 2016). The additive genetic model was selected a priori for our study, but exploration of the codominant model confirmed the association between SCC risk and the TT versus CC genotype (HR = 2.24, 95% confidence interval = 1.22–4.09, P = 0.009).…”