Abstract
IL-6 is critical for tumorigenesis. However, previous studies on the association of IL-6 promoter polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed this meta-analysis regarding the relationship between IL-6 promoter single nucleotide polymorphisms and cancer susceptibility and prognosis. Up to April 2017, 97 original publications were identified covering three IL-6 promoter SNPs. Our results showed statistically significant association between IL-6 promoter and cancer risk and prognosis. Subgroup analysis indicated that rs1800795 was significantly associated with increased risk of cervical cancer, colorectal cancer, breast cancer, prostate cancer, lung cancer, glioma, non-Hodgkin’s lymphoma and Hodgkin’s lymphoma but not gastric cancer and multiple myeloma. Furthermore, rs1800796 was significantly associated with increased risk of lung cancer, prostate cancer and colorectal cancer but not gastric cancer. Additionally, rs1800797 was significantly association with breast cancer, non-Hodgkin’s lymphoma, B-cell lymphoma and diffuse large B-cell lymphoma but not gastric cancer. Simultaneously, rs1800795 and rs1800796 were associated with a significantly higher risk of cancer in Asia and Caucasian, rs1800797 was associated with a significantly risk of cancer in Caucasian but not in Asia. Furthermore, IL-6 promoter polymorphisms were significantly associated with the prognosis of cancer. Considering these promising results, IL-6 promoter including rs1800795, rs1800796 and rs1800797 may be a tumor marker for cancer therapy.
Highlights
Interleukin-6 (IL-6) is one of the most widely recognized cytokines
Previous studies on the association of IL-6 promoter polymorphisms with predisposition to different cancer types are somewhat contradictory. We performed this meta-analysis regarding the relationship between IL-6 promoter single nucleotide polymorphisms and cancer susceptibility and prognosis
Subgroup analysis indicated that rs1800795 was significantly associated with increased risk of cervical cancer, colorectal cancer, breast cancer, prostate cancer, lung cancer, glioma, non-Hodgkin’s lymphoma and Hodgkin’s lymphoma but not gastric cancer and multiple myeloma
Summary
Interleukin-6 (IL-6) is one of the most widely recognized cytokines. It can regulate immune responses and cell proliferation and differentiation [1]. IL-6 was originally studied as an inflammatory factor, which was later found to be closely related to tumorigenesis, invasion and metastasis [2]. IL-6 is closely related to tumor occurrence and development, and understanding the genetic diversity of IL-6 will be helpful for cancer risk prediction and gene therapy. The human IL-6 gene is located on chromosome 7p21 which is identified as pro-inflammatory cytokine [6], and plays an important role in the pathogenesis of several types of cancers. Previous studies have conflicting results www.impactjournals.com/oncotarget between IL-6 promoter (rs1800795, rs1800796 and rs1800797) and cancer susceptibility [10–99] and prognosis [40, 47, 53, 57, 63, 100-106]
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