C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk
(Eklund, Tammela et al. 2009) Download
Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (alpha=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA.
C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer: results from the ASCENT trial
(Beer, Lalani et al. 2008) Download
BACKGROUND: Studies of cancer risk and molecular carcinogenesis suggest a role for inflammation in cancer development and progression. The authors sought to determine whether specific blood proteins associated with inflammation predict for outcomes in men with metastatic androgen-independent prostate cancer (AIPC) who are initiating docetaxel-based chemotherapy. METHODS: Baseline plasma samples were stored (-80 degrees C) from 160 of 250 patients enrolled in the AIPC Study of Calcitriol ENhancing Taxotere (ASCENT) trial, a randomized, placebo-controlled trial comparing weekly docetaxel plus high-dose calcitriol with weekly docetaxel. Multiplex immunoassays measured 16 cytokine, chemokine, cardiovascular, or inflammatory markers. The Cox proportional hazards model was used to assess associations between baseline biomarkers, clinical characteristics, and survival. Logistic regression was used for analyses of associations with prostate-specific antigen (PSA) decline. RESULTS: C-reactive protein (CRP) was found to be significantly predictive of a shorter overall survival (hazards ratio [HR] of 1.41 for each natural logarithm [ln] [CRP] increase; 95% confidence interval [95% CI], 1.20-1.65 [P < .0001]). When CRP (continuous) was entered into a multivariate model using 13 baseline clinical variables, only elevated CRP remained a significant predictor (P < .0001) of shorter overall survival. When categorized as normal (<or=8 mg/L) or abnormal (>8 mg/L), elevated CRP was found to be a significant predictor of shorter overall survival (HR of 2.96; 95% CI, 1.52-5.77 [P = .001]), as was hemoglobin (P = .007). Elevated CRP was also associated with a lower probability of PSA decline (odds ratio of 0.74 for each ln(CRP) increase; 95% CI, 0.60-0.92 [P = .007]). CONCLUSIONS.: Elevated plasma CRP concentrations appear to be a strong predictor of poor survival and lower probability of PSA response to treatment in patients with AIPC who are receiving docetaxel-based therapy.
C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer
(Lehrer, Diamond et al. 2005) Download
OBJECTIVE: To further analyse the relationship of c-reactive protein (CRP) levels to prostate cancer, by measuring CRP in men with prostate cancer and benign prostatic hypertrophy (BPH), as chronic inflammation has long been linked to cancers with an infectious cause and CRP is a nonspecific marker for inflammation, associated with prostate cancer incidence and progression. PATIENTS AND METHODS: Data from 114 men, most of whom had had radioactive seeds implanted, were evaluated from November 1990 to April 2002. In addition, 27 men were included who had biopsy-confirmed BPH. CRP was assessed with an automated chemiluminometric high-sensitivity assay kit. RESULTS: There was no significant difference in CRP levels in men with localized prostate cancer or BPH but levels were significantly higher in men with bone metastases. There was also a significant correlation of CRP level with prostate-specific antigen (PSA) in those with cancer. Because PSA is correlated with disease stage, multiple linear regression was used with CRP as the dependent variable, and PSA and disease stage as independent variables. The regression was significant overall (P < 0.001) and the effect of disease stage on CRP (P < 0.001) was independent of the effect of PSA level (P = 0.001). CONCLUSION: The strong association of CRP with PSA, independent of tumour stage, suggests that inflammation might be fundamental in prostate cancer, and that chronic inflammation may be a legitimate target for prostate cancer chemoprevention and treatment.
Beer, T. M., A. S. Lalani, et al. (2008). "C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer: results from the ASCENT trial." Cancer 112(11): 2377-83.
Eklund, C. M., T. L. Tammela, et al. (2009). "C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk." Br J Cancer 100(12): 1846-51.
Lehrer, S., E. J. Diamond, et al. (2005). "C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer." BJU Int 95(7): 961-2.