Statistical meta-analysis to investigate the association between the Interleukin-6 (IL-6) gene polymorphisms and cancer risk

Abstract

A good number of genome-wide association studies (GWAS), including meta-analyses, reported that single nucleotide polymorphisms (SNPs) of the IL-6 gene are significantly associated with various types of cancer risks, though some other studies reported insignificant association with cancers, in the literature. These contradictory results may be due to variations in sample sizes and/or deficiency of statistical modeling. Therefore, an attempt is made to provide a more comprehensive understanding of the association between the IL-6 gene SNPs (rs1800795, rs1800796, rs1800797) and different cancer risks, giving the weight on a large sample size, including different cancer types and appropriate statistical modeling with the meta-dataset. In order to attain a more reliable consensus decision about the association between the IL-6 gene polymorphisms and different cancer risks, in this study, we performed a multi-case statistical meta-analysis based on the collected information of 118 GWAS studies comprising of 50053 cases and 65204 control samples. Results from this Meta-analysis indicated a significant association (p-value < 0.05) of the IL-6 gene rs1800796 polymorphism with an overall increased cancer risk. The subgroup analysis data based on cancer types exhibited significant association (p-value < 0.05) of the rs1800795 polymorphism with an overall increased risk of cervical, liver and prostate cancers; the rs1800796 polymorphism with lung, prostate and stomach cancers; and the rs1800797 polymorphism with cervical cancer. The subgroup analysis of ethnicity data showed a significant association (p-value < 0.05) of an overall cancer risk with the rs1800795 polymorphism for the African and Asian populations, the rs1800796 polymorphism for the Asian only and the rs1800797 polymorphism in the African population. Comparative discussion showed that our multi-case meta-analyses received more support than any previously reported individual meta-analysis about the association between the IL-6 gene polymorphisms and cancer risks. Results from this study, more confidently showed that the IL-6 gene SNPs (rs1800795, rs1800796 and rs1800797) in humans are associated with increased cancer risks. Therefore, these three polymorphisms of the IL-6 gene have the potential to be evaluated as a population based rapid, low-cost PCR prognostic biomarkers for different types of cancers diagnosis and research.

Interleukin-1β, interleukin-6 and interleukin-10 polymorphisms in Tunisian patients with colorectal cancer and liver metastasis

“…For IL-10 (-592 C>A), comparison of genotype frequencies between CRC cases and healthy controls showed that carriers of the C/A genotype were negatively associated with CRC occurrence. This was consistent with the meta-analysis conducted in a Chinese population where it was stated that this variant was associated with a significantly reduced CRC risk [31]; similar findings were reported in an ethnic Kashmiri population where the carriers of the minor allele A were associated with a reduced CRC risk [40]. Conversely, two meta-analyses found no correlation [24,41].…”

“…In this context, the pro-and anti-inflammatory interleukins IL-1β, IL-6 and IL-10 are the most involved in the development of these neoplasms and are activated by various signaling pathways during CRC progression, supporting their crucial role in pathogenesis [7,12,13]. In this regard, several studies have reported the association of different interleukin gene polymorphisms, particularly those involved in modulating cytokine expression, such as IL-1β (-31C>T), IL-6 (-174G>C) and IL-10 (-592C>A) variants with CRC risk [24,[29][30][31][32]. However, to date there have been only a few studies focusing on CRLM.…”

Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

“…Therefore, a consensus decision about the association of HIF1A gene polymorphisms with multiple disease risk is required to make a treatment plan against this genetic effect. To make a consensus decision about the contradictory findings of different studies more accurately, researchers usually consider statistical meta-analysis [ 15 , 55 – 60 ]. The meta-analysis makes a decision about the association more accurately compared to SGA studies.…”

Role of IGF2 in the Study of Development and Evolution of Prostate Cancer

“…Additionally, recent data support the role of several SNPs in IL-6 (Interleukin 6) gene (rs1800795, rs1800796 and rs1800797) as biomarkers of an increased cancer risk in several tumors. Specially, variants rs1800795 and rs1800796 are associated with an overall increased risk of PC ( Harun-Or-Roshid et al, 2021 ).…”