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

Area of Science:

• Genetics
• Oncology
• Epidemiology

Background:

• Interleukin-6 (IL-6) is implicated in cancer progression and severity.
• The causal relationship between circulating IL-6 and cancer risk remains uncertain.

Purpose of the Study:

• To investigate the causal relevance between circulating IL-6 and cancer risk.
• Utilize a Mendelian randomization approach employing the IL-6 gene -174G/C variant.

Main Methods:

• Meta-analysis of published articles on the -174G/C variant and cancer risk.
• Meta-analysis of articles on the -174G/C variant and circulating IL-6 levels.
• Mendelian randomization analysis to assess causality.

Main Results:

• Overall, no significant association was found between the -174G/C variant and cancer risk.
• In Asians, the -174CC genotype was associated with a 1.95-fold increased cancer risk.
• The -174C allele showed a reduced risk for liver cancer (OR=0.74).
• Carriers of the -174CC genotype and -174C allele had significantly reduced circulating IL-6 levels.
• A 1 pg/mL reduction in IL-6 was associated with a 12% reduced risk of liver cancer.

Conclusions:

• Genetically reduced circulating IL-6 may be causally linked to a lower risk of liver cancer.
• The IL-6 -174G/C polymorphism influences IL-6 levels and potentially liver cancer risk.