Association Between Baseline C-Reactive Protein and the Risk of Lung Cancer: A Prospective Population-Based Cohort Study

Yin, Jian; Wang, Gang; Wu, Zheng; Lyu, Zhangyan; Su, Kai; Li, Fang; Feng, Xiaoshuang; Guo, Lanwei; Chen, Yuheng; Xie, Shuanghua; Cui, Hong; Li, Jiang; Ren, Jiansong; Shi, Jufang; Chen, Shuohua; Wang, Anxin; Dai, Min; Li, Ni; He, Jie

doi:10.1158/1940-6207.capr-21-0533

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Our study was conducted in predominantly never-smokers and light-smokers and our observed inverse DEE-CRP association is consistent with some previous evidence linking lower CRP levels to increased lung cancer risk among never-smokers 8 34. Previous prospective cohort studies have suggested effect modification of CRP-lung cancer associations by smoking status, histological subtype and potentially sex 8 34–38. The seminal meta-analysis in the Lung Cancer Cohort Consortium found positive associations between CRP and lung cancer risk among former smokers and current smokers, and inverse associations among never-smokers 34.…”

Section: Discussionsupporting

confidence: 91%

Alterations to biomarkers related to long-term exposure to diesel exhaust at concentrations below occupational exposure limits in the European Union and the USA

et al. 2023

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BackgroundWe previously found that occupational exposure to diesel engine exhaust (DEE) was associated with alterations to 19 biomarkers that potentially reflect the mechanisms of carcinogenesis. Whether DEE is associated with biological alterations at concentrations under existing or recommended occupational exposure limits (OELs) is unclear.MethodsIn a cross-sectional study of 54 factory workers exposed long-term to DEE and 55 unexposed controls, we reanalysed the 19 previously identified biomarkers. Multivariable linear regression was used to compare biomarker levels between DEE-exposed versus unexposed subjects and to assess elemental carbon (EC) exposure-response relationships, adjusted for age and smoking status. We analysed each biomarker at EC concentrations below the US Mine Safety and Health Administration (MSHA) OEL (<106 µg/m3), below the European Union (EU) OEL (<50 µg/m3) and below the American Conference of Governmental Industrial Hygienists (ACGIH) recommendation (<20 µg/m3).ResultsBelow the MSHA OEL, 17 biomarkers were altered between DEE-exposed workers and unexposed controls. Below the EU OEL, DEE-exposed workers had elevated lymphocytes (p=9E-03, false discovery rate (FDR)=0.04), CD4+ count (p=0.02, FDR=0.05), CD8+ count (p=5E-03, FDR=0.03) and miR-92a-3p (p=0.02, FDR=0.05), and nasal turbinate gene expression (first principal component: p=1E-06, FDR=2E-05), as well as decreased C-reactive protein (p=0.02, FDR=0.05), macrophage inflammatory protein-1β (p=0.04, FDR=0.09), miR-423-3p (p=0.04, FDR=0.09) and miR-122-5p (p=2E-03, FDR=0.02). Even at EC concentrations under the ACGIH recommendation, we found some evidence of exposure-response relationships for miR-423-3p (ptrend=0.01, FDR=0.19) and gene expression (ptrend=0.02, FDR=0.19).ConclusionsDEE exposure under existing or recommended OELs may be associated with biomarkers reflective of cancer-related processes, including inflammatory/immune response.

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Section: Discussionsupporting

confidence: 91%

Alterations to biomarkers related to long-term exposure to diesel exhaust at concentrations below occupational exposure limits in the European Union and the USA

et al. 2023

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Association between C-reactive protein variability and cancer incidence: a longitudinal prospective cohort study

Chen,

Wang,

Zheng

et al. 2024

Preprint

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Background The association between inflammation and cancer has been widely studied, but research on the relationship between the magnitude of inflammatory fluctuations and cancer remains limited. Therefore, this study aims to investigate the association between C-reactive protein (CRP) variability and the occurrence of cancer. Methods A total of 42,514 participants were included, and their CRP levels were measured over a 4-year period. We used the coefficient of variation (CV) of CRP to quantify the variability in inflammation. Cox regression analysis was used to assess the association between CRP variability and cancer risk after adjusting for potential confounding factors. Results High CV of CRP significantly associated with reduced cancer risk (hazard ratio (HR) = 0.84; 95% CI: 0.75–0.94, P = 0.003). Participants with high CRP and low CV had a significantly increased risk of cancer (HR = 1.42; 95% CI: 1.18–1.70, P < 0.001). In the population with long-term stable CRP levels, there is a significant association between the CV and the risk of cancer (HR = 0.81; 95% CI: 0.72–0.92, P = 0.001). Furthermore, the association between the CV and lung cancer was most pronounced. Sensitivity analyses confirmed the stability of the association between CRP variability and cancer. Conclusion High CRP variability is significantly associated with reduced risk of cancer, particularly in the case of lung cancer. This provides a new perspective and evidence for exploring the relationship between inflammation and cancer.

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Mendelian randomization study of the relationship between blood and urine biomarkers and lung cancer

Huang,

Zheng

2024

Front. Oncol.

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IntroductionIdentifying suitable biomarkers is crucial for exploring the pathogenesis, early screening, and therapeutic monitoring of lung cancer. This study aims to analyze comprehensively the associations between lung cancer and biomarkers in blood and urine.MethodsBidirectional two-sample Mendelian randomization (MR) was used to evaluate the potential causal relationships between blood and urine biomarkers and lung cancer. We obtained Single nucleotide polymorphisms (SNPs) related to lung cancer from the 2021 Finnish database of genome-wide association studies, including small cell lung cancer (SCLC), total non-small cell lung cancer (NSCLC), lung adenocarcinoma (LAC), and lung squamous cell carcinoma (LSCC).Data on blood and urine biomarkers were derived from the UK Biobank cohort, comprising 376,807 participants.ResultsWe found a potential inverse causal relationship between total bilirubin and SCLC (β=-0.285, P=0.015, FDR=0.12). Urate was inversely associated with NSCLC (β=-0.158, P=0.004, FDR=0.036*). Serum calcium showed a possible inverse relationship with lung squamous cell carcinoma (β=-0.256, P=0.046, FDR=0.138), while urinary creatinine was positively associated (β=1.233, P=0.024, FDR=0.216). Non-albumin proteins (β=-0.272, P=0.020, FDR=0.180) and total protein (β=-0.402, P=0.009, FDR=0.072) were inversely related to lung squamous cell carcinoma. The AST/ALT ratio was positively associated with lung adenocarcinoma (β=0.293, P=0.009, FDR=0.072). Our reverse Mendelian randomization study found a positive causal association between small cell lung cancer and serum creatinine (β=0.022, P=0.002, FDR=0.018*), while it was inversely associated with the estimated glomerular filtration rate(eGFR)(β=-0.022, P=0.003, FDR=0.027*). A positive causal relationship was also observed with cystatin C (β=0.026, P=0.005, FDR=0.045*) and glycated hemoglobin HbA1c (β=0.013, P=0.014, FDR=0.028*). A negative causal relationship was observed with Gamma_glutamyltransferase (β=-0.013, P=0.019, FDR=0.152). For non-small cell lung cancer, a negative causal relationship was found with albumin (β=-0.024, P=0.002, FDR=0.016*), while a potentially positive causal relationship was observed with cystatin C (β=0.022, P=0.006, FDR=0.054). Possible negative causal relationships were also observed with phosphate (β=-0.013, P=0.008, FDR=0.072) and urinary potassium (β=-0.011, P=0.012, FDR=0.108), while a potential positive causal relationship was observed with C-reactive protein (β=0.013, P=0.040, FDR=0.280).Regarding lung squamous cell carcinoma, an inverse causal relationship was found with eGFR (β=-0.022, P=9.58e-06, FDR=8.62×10-5*), while a positive causal relationship was observed with serum creatinine (β=0.021, P=1.16e−4, FDR=1.05×10-3*). Potential positive causal relationships were observed with Urate (β=0.012, P=0.020, FDR=0.180), urea (β=0.010, P=0.046, FDR=0.141), and glycated hemoglobin HbA1c (β=0.020, P=0.049, FDR P=0.098), whereas a potential negative causal relationship was observed with sex hormone-binding globulin(SHBG) (β=-0.020, P=0.036, FDR=0.108).Lastly, adenocarcinoma was found to have a positive causal association with alkaline phosphatase (β=0.015, P=0.006, FDR=0.033*).ConclusionOur study provides a robust theoretical basis for the early screening and therapeutic monitoring of lung cancer and contributes to understanding the pathogenesis of the disease.

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Association Between Baseline C-Reactive Protein and the Risk of Lung Cancer: A Prospective Population-Based Cohort Study

Cited by 3 publications

References 36 publications

Alterations to biomarkers related to long-term exposure to diesel exhaust at concentrations below occupational exposure limits in the European Union and the USA

Alterations to biomarkers related to long-term exposure to diesel exhaust at concentrations below occupational exposure limits in the European Union and the USA

Association between C-reactive protein variability and cancer incidence: a longitudinal prospective cohort study

Mendelian randomization study of the relationship between blood and urine biomarkers and lung cancer

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