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

• Published in: International journal of cancer Vol. 134; no. 1; pp. 154 - 163
• Main Authors: Ohishi, Waka, Cologne, John B., Fujiwara, Saeko, Suzuki, Gen, Hayashi, Tomonori, Niwa, Yasuharu, Akahoshi, Masazumi, Ueda, Keiko, Tsuge, Masataka, Chayama, Kazuaki
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.01.2014; Wiley Subscription Services, Inc
• Subjects: Alcohol; Biological and medical sciences; Biomarkers, Tumor - blood; Body mass index; Cancer; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - complications; Case-Control Studies; Cytokines; C‐reactive protein; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis; hepatocellular carcinoma; Humans; Infections; Interleukin-6 - blood; interleukin‐6; Life Style; Liver cancer; Liver Neoplasms - blood; Liver Neoplasms - complications; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical research; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms, Radiation-Induced - blood; nested case–control study; Nuclear Weapons; Obesity; Obesity - complications; Risk Factors; Survivors; Tumors; Obesity; C-reactive protein; Cytokine; Nutrition disorder; Hepatic disease; Hepatocellular carcinoma; Risk; nested case-control study; Malignant tumor; Case control study; interleukin-6; Interleukin 6; Liver cancer; Acute phase protein; Association; Cancerology; Risk factor; Digestive diseases; Serum; C reactive protein; Nutritional status; Cancer; hepatocellular carcinoma; obesity
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.28337

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. What's new? According to previous research, alcohol consumption, obesity, and radiation exposure as well as hepatitis virus infection are all independent risk factors for hepatocellular carcinoma (HCC). Inflammatory markers have also been associated with increased risk of liver cancer, but the evidence is inconsistent. In this nested case‐control study in the longitudinal cohort of atomic‐bomb survivors, which took into account hepatitis virus infection, lifestyle‐related factors, and radiation exposure, elevated IL‐6 levels were found to be associated with increased risk of HCC. The findings also indicated that association of IL‐6 levels with increased risk of HCC is especially pronounced among subjects with obesity.