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Non-Malignant Drivers of Elevated C-Reactive Protein Levels Differ in Patients With and Without a History of Cancer

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Abstract

Purpose: Elevations in C-reactive protein (CRP) levels predict metastasis and mortality in a number of malignancies. However, the impact of non-malignant factors on CRP levels in patients with cancer remains unknown. To address this issue, we conducted an investigation of the National Social Life, Health, and Aging Project (NSHAP) cohort.

Methods: NSHAP participants with a history of malignancy were included. The 222-participant cohort was subdivided by CRP levels into low-risk (CRP <3 mg/L) and high-risk (CRP ≥3 mg/L) groups. Univariate and multivariate binary logistic regression analyses examined the impact of variables spanning social factors, demographic characteristics, and past medical history on high-risk CRP levels.

Results: Of the cohort, 42.3% exhibited high-risk CRP levels. These participants were more likely to be unmarried (p = 0.013), to be a racial/ethnic minority (p = 0.012), to not use HMG-CoA reductase inhibitor (statin) medications (p = 0.032), and to be obese (p = 0.002). On multivariate logistic regression analysis, these variables were also significant predictors of high-risk CRP levels. For example, compared with participants who had a normal body mass index (BMI), obese participants were nearly 5 times more likely (odds ratio 5.725; 95% CI 1.848, 12.079; p = 0.001) to exhibit high-risk CRP levels.

Conclusions: CRP remains an important prognostic biomarker in the management of known malignancies. However, patients with a known history of cancer can also exhibit elevated CRP levels due to non-malignant factors such as race and ethnicity, statin use, marital status, and BMI. Consequently, further studies are needed to assess the predictive potential of CRP levels for cancer prognostication in the face of these social and biologic variables before use of this biomarker is widely adopted in clinical practice.

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References

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009; 59: 225–49

    Article  PubMed  Google Scholar 

  2. Canna K, McMillan DC, McKee RF, et al. Evaluation of a cumulative prognostic score based on the systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer. Br J Cancer 2004; 90: 1707–9

    PubMed  CAS  Google Scholar 

  3. Jabs WJ, Busse M, Kruger S, et al. Expression of C-reactive protein by renal cell carcinomas and unaffected surrounding renal tissue. Kidney Int 2005; 68: 2103–10

    Article  PubMed  CAS  Google Scholar 

  4. McKeown DJ, Brown DJ, Kelly A, et al. The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. Br J Cancer 2004; 91: 1993–5

    Article  PubMed  CAS  Google Scholar 

  5. Gagnon B, Abrahamowicz M, Xiao Y, et al. Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer. Br J Cancer 2010; 102: 1113–22

    Article  PubMed  CAS  Google Scholar 

  6. Hefler-Frischmuth K, Seebacher V, Polterauer S, et al. The inflammation-based modified Glasgow Prognostic Score in patients with vulvar cancer. Eur J Obstet Gynecol Reprod Biol 2010; 149: 102–5

    Article  PubMed  Google Scholar 

  7. Johnson TV, Abbasi A, Owen-Smith A, et al. Absolute preoperative C-reactive protein predicts metastasis and mortality in the first year following potentially curative nephrectomy for clear cell renal cell carcinoma. J Urol 2010; 183: 480–5

    Article  PubMed  CAS  Google Scholar 

  8. Johnson TV, Abbasi A, Owen-Smith A, et al. Postoperative better than preoperative C-reactive protein at predicting outcome after potentially curative nephrectomy for renal cell carcinoma. Urology 2010 Sep; 76(3): 766.e1–5

    Article  CAS  Google Scholar 

  9. Ljungberg B. Prognostic markers in renal cell carcinoma. Curr Opin Urol 2007; 17: 303–8

    Article  PubMed  Google Scholar 

  10. Iimura Y, Saito K, Fujii Y, et al. Development and external validation of a new outcome prediction model for patients with clear cell renal cell carcinoma treated with nephrectomy based on preoperative serum C-reactive protein and TNM classification: the TNM-C score. J Urol 2009 Mar; 181(3): 1004–12; discussion 1012

    Article  PubMed  Google Scholar 

  11. Karakiewicz PI, Hutterer GC, Trinh QD, et al. C-reactive protein is an informative predictor of renal cell carcinoma-specific mortality: a European study of 313 patients. Cancer 2007; 110: 1241–7

    Article  PubMed  CAS  Google Scholar 

  12. Ramsey S, Lamb GW, Aitchison M, et al. Prospective study of the relationship between the systemic inflammatory response, prognostic scoring systems and relapse-free and cancer-specific survival in patients undergoing potentially curative resection for renal cancer. BJU Int 2008; 101: 959–63

    Article  PubMed  CAS  Google Scholar 

  13. Johnson TV, Young AN, Osunkoya AO, et al. C-reactive protein as a clinically useful biomarker of metastasis of renal cell carcinoma. Mol Diagn Ther 2010; 14(3): 191–3

    Article  PubMed  Google Scholar 

  14. Tatokoro M, Saito K, Iimura Y, et al. Prognostic impact of postoperative C-reactive protein level in patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy. J Urol 2008; 180: 515–9

    Article  PubMed  CAS  Google Scholar 

  15. Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 2007; 21: 901–12

    Article  PubMed  CAS  Google Scholar 

  16. Johnson T, Abbasi A, Ehrlich S, et al. Nocturia associated with depressive symptoms. Urology. Epub 2010 Jul 2

  17. Johnson T, Abbasi A, Ehrlich S, et al. Major depression drives severity of American Urological Association Symptom Score. Urology. In press

  18. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24–31

    Article  PubMed  CAS  Google Scholar 

  19. Suzman R. The National Social Life, Health, and Aging Project: an introduction. J Gerontol B Psychol Sci Soc Sci 2009; 64Suppl. 1: i5–11

    Article  PubMed  Google Scholar 

  20. Sbarra DA. Marriage protects men from clinically meaningful elevations in C-reactive protein: results from the National Social Life, Health, and Aging Project (NSHAP). Psychosom Med 2009; 71: 828–35

    Article  PubMed  CAS  Google Scholar 

  21. Heikkila K, Ebrahim S, Lawlor DA. A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health 2007; 61: 824–33

    Article  PubMed  Google Scholar 

  22. Allin KH, Nordestgaard BG, Zacho J, et al. C-reactive protein and the risk of cancer: a Mendelian randomization study. J Natl Cancer Inst 2010; 102: 202–6

    Article  PubMed  CAS  Google Scholar 

  23. Ford ME, Kelly PA. Conceptualizing and categorizing race and ethnicity in health services research. Health Serv Res 2005; 40: 1658–75

    Article  PubMed  Google Scholar 

  24. Fullilove MT. Deconstructing race in medical research. Arch Pediatr Adolesc Med 1994; 148: 1014–5

    Article  PubMed  CAS  Google Scholar 

  25. LaVeist TA. Beyond dummy variables and sample selection: what health services researchers ought to know about race as a variable. Health Serv Res 1994; 29: 1–16

    PubMed  CAS  Google Scholar 

  26. McDade TW, Hawkley LC, Cacioppo JT. Psychosocial and behavioral predictors of inflammation in middle-aged and older adults: the Chicago Health, Aging, and Social Relations Study. Psychosom Med 2006; 68: 376–81

    Article  PubMed  Google Scholar 

  27. Kelley-Hedgepeth A, Lloyd-Jones DM, Colvin A, et al. Ethnic differences in C-reactive protein concentrations. Clin Chem 2008; 54: 1027–37

    Article  PubMed  CAS  Google Scholar 

  28. Goodwin JS, Hunt WC, Key CR, et al. The effect of marital status on stage, treatment, and survival of cancer patients. JAMA 1987; 258: 3125–30

    Article  PubMed  CAS  Google Scholar 

  29. Johnson NJ, Backlund E, Sorlie PD, et al. Marital status and mortality: the National Longitudinal Mortality Study. Ann Epidemiol 2000; 10: 224–38

    Article  PubMed  CAS  Google Scholar 

  30. Johnson T, Master V. Separated and other unmarried patients experience higher rates of cancer-specific mortality: a SEER Database study. Cancer. In press

  31. Sprehn GC, Chambers JE, Saykin AJ, et al. Decreased cancer survival in individuals separated at time of diagnosis: critical period for cancer pathophysiology? Cancer 2009; 115: 5108–16

    Article  PubMed  Google Scholar 

  32. Kiecolt-Glaser JK, McGuire L, Robles TF, et al. Psychoneuroimmunology and psychosomatic medicine: back to the future. Psychosom Med 2002; 64: 15–28

    PubMed  Google Scholar 

  33. O’Reilly DS, Upton MN, Caslake MJ, et al. Plasma C reactive protein concentration indicates a direct relation between systemic inflammation and social deprivation. Heart 2006; 92: 533–5

    Article  PubMed  Google Scholar 

  34. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195–207

    Article  PubMed  CAS  Google Scholar 

  35. Eder K, Baffy N, Falus A, et al. The major inflammatory mediator interleukin-6 and obesity. Inflamm Res 2009; 58: 727–36

    Article  PubMed  CAS  Google Scholar 

  36. Wilson AM, Ryan MC, Boyle AJ. The novel role of C-reactive protein in cardiovascular disease: risk marker or pathogen. Int J Cardiol 2006; 106: 291–7

    Article  PubMed  Google Scholar 

  37. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 2009; 12: 223–6

    Article  PubMed  Google Scholar 

  38. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol 2010; 6: 149–63

    Article  PubMed  CAS  Google Scholar 

  39. Erlinger TP, Platz EA, Rifai N, et al. C-reactive protein and the risk of incident colorectal cancer. JAMA 2004; 291: 585–90

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

No sources of funding were used to conduct this study or prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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  1. Department of Urology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA

    Timothy V. Johnson & Viraj A. Master

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  1. Timothy V. Johnson
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  2. Viraj A. Master
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Correspondence to Timothy V. Johnson.

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Johnson, T.V., Master, V.A. Non-Malignant Drivers of Elevated C-Reactive Protein Levels Differ in Patients With and Without a History of Cancer. Mol Diag Ther 14, 295–303 (2010). https://doi.org/10.1007/BF03256385

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