The link between IL-6 rs2069840 SNP and cancer risk: Evidence from a systematic review and meta-analysis

Cancer is the second leading global health burden in terms of incidence and mortality. The association between IL-6 rs2069840 variant and cancer risk has been evaluated previously by genome-wide association studies and case-control studies, but the results remained controversial. Our present meta-analysis aimed to reveal the association of IL-6 rs2069840 polymorphism with cancer risk for the first time. Review Manager 5.4 software was used for performing the meta-analysis, and heterogeneity was assessed using I². A total of 13 retrospective studies with 22,487 cases and 26,540 controls were selected for performing this meta-analysis. Our study showed that rs2069840 is not significantly associated with overall cancer risk. After stratification with population subgroups, no relationship was observed in Asians, Caucasians, Africans, or mixed populations. Subgroup analyses based on the cancer types revealed a significant correlation of rs2069840 with breast cancer in COD3 (OR = 1.13, p = 0.008), RM (OR = 1.10, p = 0.023), and OD (OR = 0.94, p = 0.029). A significant correlation was also found in COD1 (OR = 1.08, p = 0.020) and OD (OR = 1.07, p = 0.022) models for the development of other cancers (multiple myeloma, prostate cancer, gastric cancer). The findings of the present study suggest that IL-6 rs2069840 polymorphism is not linked with overall cancer risk. However, this polymorphism may be associated with breast cancer, multiple myeloma, prostate cancer, and gastric cancer.