Inflammatory Markers of CRP, IL6, TNFα, and Soluble TNFR2 and the Risk of Ovarian Cancer: A Meta-analysis of Prospective Studies.
There has been growing evidence showing that inflammatory markers play an important role in the development of ovarian cancer. We conducted a meta-analysis on the associations between circulating levels of C-reactive protein (CRP), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and soluble TNFα receptor 2 (TNFR2), and the risk of ovarian cancer.



A systematic search of PubMed and EMBASE up until January 19, 2016 was conducted to retrieve prospective studies. The summary risk estimates were pooled using random-effects models. The dose-response relationship was assessed using generalized least-squares trend estimation.



Seven nested case-control studies and one prospective cohort study were included in the review. For circulating CRP, women in the highest category had a significantly increased risk of ovarian cancer than women in the lowest category, with no significant between-study heterogeneity [pooled relative risk (RR) = 1.91; 95% confidence intervals (CI) 1.51-2.40; P < 0.001; I(2) = 0.0%]. Influence analyses further supported this positive association. A positive dose-response relationship was also observed (pooled RR = 1.15; 95% CI, 1.03-1.30 per 5 mg/L of CRP). Publication bias was found. However, the association persisted after correction using the trim-and-fill method. No significant association was observed for circulating IL6, TNFα, and soluble TNFR2.



This meta-analysis provides evidence that elevated levels of CRP, but not circulating IL6, TNFα, or soluble TNFR2, are significantly associated with an increased risk of ovarian cancer.



These results suggest that circulating CRP may play a role in the etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(8); 1231-9. ©2016 AACR.
School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. CUHK Shenzhen Research Institute, Shenzhen, China.
Fangfang
F
Zeng
School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. CUHK Shenzhen Research Institute, Shenzhen, China.
Huishan
H
Wei
School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. CUHK Shenzhen Research Institute, Shenzhen, China.
Engkiong
E
Yeoh
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
Zheqing
Z
Zhang
School of Public Health, Sun Yat-sen University, Guangzhou, China.
Ze-Fang
ZF
Ren
Alvin J. Siteman Cancer Center and Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
Graham A
GA
Colditz
Channing Division of Network Medicine, Harvard Medical School and the Brigham and Women's Hospital, Boston, Massachusetts. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. xuefensu@cuhk.edu.hk nhsst@channing.harvard.edu.
Shelley S
SS
Tworoger
School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. CUHK Shenzhen Research Institute, Shenzhen, China. xuefensu@cuhk.edu.hk nhsst@channing.harvard.edu.
Xuefen
X
Su
D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein