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Sci Rep. 2015 Jun 22;5:11394. doi: 10.1038/srep11394.

Circulating interleukin-6 and cancer: A meta-analysis using Mendelian randomization.

Author information

1
Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
2
Institute of Anatomy, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
3
Clinic Institute, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
4
Institute of Pharmacology, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
5
Institute of Molecular Imaging, Binzhou Medical University, Laishan District, Yantai, Shandong, China.

Abstract

Interleukin-6 (IL-6) plays a contributory role in the progression and severity of many forms of cancer; it however remains unclear whether the relevance between circulating IL-6 and cancer is causal. We therefore meta-analyzed published articles in this regard using IL-6 gene -174G/C variant as an instrument. Seventy-eight and six articles were eligible for the association of -174G/C variant with cancer and circulating IL-6, respectively. Overall analyses failed to identify any significance between -174G/C and cancer risk. In Asians, carriers of the -174CC genotype had an 1.95-fold increased cancer risk compared with the -174GG genotype carriers (P = 0.009). By cancer type, significance was only attained for liver cancer with the -174C allele conferring a reduced risk under allelic (odds ratio or OR = 0.74; P = 0.001), homozygous genotypic (OR = 0.59; P = 0.029) and dominant (OR = 0.67; P = 0.004) models. Carriers of the -174CC genotype (weighted mean difference or WMD = -4.23 pg/mL; P < 0.001) and -174C allele (WMD = -3.43 pg/mL; P < 0.001) had circulating IL-6 reduced significantly compared with the non-carriers. In further Mendelian randomization analysis, a reduction of 1 pg/mL in circulating IL-6 was significantly associated with an 12% reduced risk of liver cancer. Long-term genetically-reduced circulating IL-6 might be causally associated with a lower risk of liver cancer.

PMID:
26096712
PMCID:
PMC4476043
DOI:
10.1038/srep11394
[Indexed for MEDLINE]
Free PMC Article

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