Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Baiziting 42, Nanjing, China.
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Rd, Nanjing, 211166, China.
BMC Med. 2022 Sep 19;20(1):301. doi: 10.1186/s12916-022-02506-x.
Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations.
We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them.
During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P < 0.001 and FDR-adjusted P < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P < 0.050 and FDR-adjusted P > 0.050). In addition, we also observed three different patterns of non-linear associations, including "fast-to-low increase" (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), "increase-to-decrease" (breast cancer), and "decrease-to-platform" (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers.
Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.
尽管观察性研究报告了血清 C 反应蛋白（CRP）浓度与肺癌、乳腺癌和结直肠癌风险之间的关联，但其他癌症的证据不一致或不存在。我们进行了泛癌分析，以全面评估 CRP 的作用，包括线性和非线性关联。
我们分析了来自英国生物库队列的 420964 名无癌症参与者。使用多变量调整的 Cox 比例风险模型评估 CRP 与总体癌症和 21 个部位特异性癌症风险的观察相关性。此外，我们进行了线性和非线性 Mendelian 随机化分析，以探讨它们之间潜在的因果关系。
在中位随访 7.1 年（四分位距：6.3，7.7）期间，观察到 34979 例新发癌症病例。观察性分析表明，较高的 CRP 浓度与总体癌症风险增加相关（风险比（HR）= 1.02，95%CI：1.01，1.02，每增加 1mg/L，P < 0.001）。CRP 与总体癌症风险之间存在非线性关联，拐点为 3mg/L（假发现率调整（FDR 调整）P < 0.001 和 FDR 调整 P < 0.001）。对于部位特异性癌症，我们观察到食管和胃癌症呈阳性线性关联（FDR 调整 P < 0.050 和 FDR 调整 P > 0.050）。此外，我们还观察到三种不同的非线性关联模式，包括“快速到低增加”（头颈部、结直肠、肝脏、肺部、肾脏癌症和非霍奇金淋巴瘤）、“增加到减少”（乳腺癌）和“减少到平台”（慢性淋巴细胞白血病）。此外，非线性关联模式的拐点均约为 3mg/L。相比之下，遗传预测的 CRP 与总体癌症或部位特异性癌症风险之间没有线性或非线性关联的证据。
我们的研究结果表明，CRP 是评估总体癌症和 12 种部位特异性癌症风险的潜在生物标志物，而遗传预测的 CRP 与癌症风险之间没有关联。
