C-Reactive Protein Levels, Variation in the C-Reactive Protein Gene, and Cancer Risk: The Rotterdam Study

PurposeIt remains unclear if inflammation itself may induce cancer, if inflammation is a result of tumor growth, or a combination of both exists. The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer.Patients and MethodsA total of 7,017 participants age ≥ 55 years from the Rotterdam Study were eligible for analyses. Mean follow-up time was 10.2 years. High-sensitivity CRP measurements were performed to identify additional values of 0.2 to 1.0 mg/L compared with standard procedures. Genotypes of the CRP gene were determined with an allelic discrimination assay.ResultsHigh levels (> 3 mg/L) of CRP were associated with an increased risk of incident cancer (hazard ratio, 1.4; 95% CI, 1.1 to 1.7) compared with persons with low levels (< 1 mg/L), even after a potential latent period of 5 years was introduced. Although CRP seems to affect several cancer sites, the association was strongest for lung cancer (hazard ratio, 2.8; 95% CI, 1.6 to 4.9). A CRP single nucleotide polymorphism associated with decreased CRP levels was associated with an increased lung cancer risk of 2.6 (95% CI, 1.6 to 4.4) in homozygous carriers.ConclusionBaseline CRP levels seem to be a biomarker of chronic inflammation preceding lung cancer, even after subtracting a 5-year latent period. Furthermore, CRP gene variation associated with low CRP blood levels was relatively common in patients with lung cancer. Both chronic inflammation and impaired defense mechanisms resulting in chronic inflammation might explain these results.

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Abstract 825: Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions

10.1158/1538-7445.am2021-825 ◽

2021 ◽

Author(s):

Su Yon Jung ◽

Herbert Yu ◽

Matteo Pellegrini ◽

Jeanette C. Papp ◽

Eric M. Sobel ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Chronic Inflammation ◽

Mendelian Randomization ◽

Colorectal Cancer Risk ◽

Primary Colorectal Cancer ◽

C Reactive Protein ◽

Protein Levels ◽

Reactive Protein ◽

Genetically Determined

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Gulf War Illness-associated increases in blood levels of interleukin 6 and C-reactive protein: biomarker evidence of inflammation

BMC Research Notes ◽

10.1186/s13104-019-4855-2 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 4

Author(s):

Tammy A. Butterick ◽

Janeen H. Trembley ◽

Laura L. Hocum Stone ◽

Clemma J. Muller ◽

Rebecca R. Rudquist ◽

...

Keyword(s):

Chronic Inflammation ◽

Interleukin 6 ◽

Well Being ◽

Gulf War ◽

Blood Levels ◽

C Reactive Protein ◽

Gulf War Illness ◽

Memory Impairments ◽

Reactive Protein ◽

Gastrointestinal Problems

Abstract Objective Gulf War Illness is a chronic multisymptom disorder severely impacting the health and well-being of many Veterans of the 1990–1991 Gulf War. Symptoms that define the disease include pain, fatigue, mood and memory impairments, gastrointestinal problems, lung disorders, and skin rashes. In our previous biomarker study, we discovered Gulf War Illness-associated proinflammatory blood biomarkers. Therefore, we hypothesized that chronic inflammation causes the symptoms that define this disorder. Testing the chronic inflammation hypothesis is the objective of this study. Results The biomarker fingerprint of Gulf War Illness is the end-product of a cascade of proinflammatory cytokine signals. In particular, the observed increase in C-reactive protein predicts a corresponding increase in interleukin 6, the cytokine that stimulates hepatocytes to produce C-reactive protein. Therefore, in this study we measured potential upstream cytokine signals in plasma samples from Gulf War Veterans. As predicted, a positive correlation between interleukin 6 and C-reactive protein was observed.

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Cardiorespiratory fitness, C-reactive protein and lung cancer risk: A prospective population-based cohort study

European Journal of Cancer ◽

10.1016/j.ejca.2015.04.020 ◽

2015 ◽

Vol 51 (11) ◽

pp. 1365-1370 ◽

Cited By ~ 6

Author(s):

Perfenia Paul Pletnikoff ◽

Jari A. Laukkanen ◽

Tomi-Pekka Tuomainen ◽

Jussi Kauhanen ◽

Rainer Rauramaa ◽

...

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

Cancer Risk ◽

Cardiorespiratory Fitness ◽

Lung Cancer Risk ◽

Population Based ◽

C Reactive Protein ◽

Reactive Protein

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C-reactive protein gene 1846C>T polymorphism is associated with increased risk and clinical features of lung cancer: a case–control study

Bioscience Reports ◽

10.1042/bsr20181936 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 2

Author(s):

Chen Chen ◽

Jing-Ni Liu ◽

Jian-Qiang Zhao ◽

Bao Zang

Keyword(s):

Lung Cancer ◽

Case Control Study ◽

Case Control ◽

Lung Carcinogenesis ◽

C Reactive Protein ◽

Chinese Han ◽

Reactive Protein ◽

Potential Marker ◽

Increased Risk ◽

Control Study

AbstractChronic inflammation plays an important role in lung carcinogenesis. Recently, several studies investigated the association of C-reactive protein (CRP) gene 1846C>T polymorphism and lung cancer (LC) risk, but with conflicting findings. In the present study, we conducted this case–control study with 408 LC patients and 472 healthy controls in a Chinese Han population. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLR) method. Our data found that CRP gene 1846C>T polymorphism increased the risk of LC. Subgroup analyses obtained significant associations among the groups of males, ≥50 years old, smoking, and non-drinkers. Bioinformatics analysis showed that the expression levels of CRP in LC tissues were significantly increased compared with normal tissues. Additionally, the present study found CRP mRNA high expression was associated with worse survival in LC patients. Furthermore, our data indicated that TT genotype of 1846C>T polymorphism was associated with a larger size of tumor and was related with lymphatic metastasis in LC patients. In conclusion, the present study suggests that CRP gene 1846C>T polymorphism is associated with increased risk of LC. CRP gene 1846C>T polymorphism may be a potential marker for the diagnosis of LC.

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C-Reactive Protein and Risk of Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.0454 ◽

2010 ◽

Vol 28 (16) ◽

pp. 2719-2726 ◽

Cited By ~ 121

Author(s):

Anil K. Chaturvedi ◽

Neil E. Caporaso ◽

Hormuzd A. Katki ◽

Hui-Lee Wong ◽

Nilanjan Chatterjee ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Lung Cancer Risk ◽

Smoking Status ◽

Lung Carcinogenesis ◽

C Reactive Protein ◽

Baseline Serum ◽

Reactive Protein ◽

Former Smokers

Purpose Chronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk. Patients and Methods We conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs. Results Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend < .001 for fourth quartile [Q4, ≥ 5.6 mg/L] v Q1 [< 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%). Conclusion Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.

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C-Reactive Protein, Interleukin 6 and Lung Cancer Risk: A Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0043075 ◽

2012 ◽

Vol 7 (8) ◽

pp. e43075 ◽

Cited By ~ 39

Author(s):

Bo Zhou ◽

Jing Liu ◽

Ze-Mu Wang ◽

Tao Xi

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Interleukin 6 ◽

Lung Cancer Risk ◽

Meta Analysis ◽

C Reactive Protein ◽

Reactive Protein

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Cerebrovascular comorbidity, high blood levels of C - reactive protein and D-dimer are associated with disease outcomes in COVID-19 patients

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-201002 ◽

2020 ◽

pp. 1-12

Author(s):

Foad Alzoughool ◽

Lo’ai Alanagreh ◽

Suhad Abumweis ◽

Manar Atoum

Keyword(s):

Case Reports ◽

Meta Analysis ◽

Serum Levels ◽

Blood Levels ◽

C Reactive Protein ◽

Reactive Protein ◽

Cerebrovascular Complications ◽

Increased Risk ◽

Risk Of Disease ◽

D Dimer

The emerging coronavirus disease (COVID-19) swept the world, affecting more than 200 countries and territories. As of August 22, 2020, the pandemic infected more than 23,329,752 including 807,054 patients who have died. Although the main clinical features of the pandemic disease are respiratory, cerebrovascular comorbidities emerged as one of the leading causes of death associated with COVID-19. Different case reports have indicated that C-reactive protein (CRP) and D-dimer (pro-inflammatory biomarkers) were elevated in COVID-19 patients, which can significantly increase the risk of ischemic stroke. Available data on cerebrovascular complications in COVID-19 patients were collected and a meta-analysis was designed and carried out to evaluate the risk of severity and mortality associated with high levels of CRP and D-dimer levels in COVID-19 patients. In addition, we aimed to describe the overall event rate of pre-existing cerebrovascular disease in COVID-19 patients. In our analysis, 5,614 cases have been studied, out of these patients 164 cases have developed cerebrovascular comorbities. Cerebrovascular comorbidity increased the risk of disease severity (odd ratio = 4.4; 95% CI: 1.48 to 12.84) and mortality (odd ratio = 7.0; 95% CI: 2.56 to 18.99). Statistical analyses showed that CRP and D-dimer serum levels were elevated by six-folds in the severe cases of COVID-19 patients. This significant increase in these two proteins levels can serve as a vital indicator for COVID-19 patients who are at increased risk of severe COVID-19 cerebrovascular complications, such as stroke.

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