Serum interleukin‐6 associated with hepatocellular carcinoma risk: A nested case–control study

Inflammatory markers have been associated with increased risk of several cancers, including colon, lung, breast and liver, but the evidence is inconsistent. We conducted a nested case–control study in the longitudinal cohort of atomic‐bomb survivors. The study included 224 hepatocellular carcinoma (HCC) cases and 644 controls individually matched to cases on gender, age, city and time and method of serum storage, and countermatched on radiation dose. We measured C‐reactive protein (CRP) and interleukin (IL)‐6 using stored sera obtained within 6 years before HCC diagnosis from 188 HCC cases and 605 controls with adequate volumes of donated blood. Analyses with adjustment for hepatitis virus infection, alcohol consumption, smoking habit, body mass index (BMI) and radiation dose showed that relative risk (RR) of HCC 95% confidence interval (CI)] in the highest tertile of CRP levels was 1.94 (0.72–5.51) compared to the lowest tertile (p = 0.20). RR of HCC (95% CI) in the highest tertile of IL‐6 levels was 5.12 (1.54–20.1) compared to the lowest tertile (p = 0.007). Among subjects with BMI > 25.0 kg/m², a stronger association was found between a 1‐standard deviation (SD) increase in log IL‐6 and HCC risk compared to subjects in the middle quintile of BMI (21.3–22.9 kg/m²), resulting in adjusted RR (95% CI) of 3.09 (1.78–5.81; p = 0.015). The results indicate that higher serum levels of IL‐6 are associated with increased HCC risk, independently of hepatitis virus infection, lifestyle‐related factors and radiation exposure. The association is especially pronounced among subjects with obesity.