Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study

Abstract

Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02-1.86) and overall death (HR : 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.

Inflammatory serum markers and risk and severity of prostate cancer: The PROCA‐life study

“…Results from previous studies of the association between hs-CRP or WBC and prostate cancer risk have been inconsistent. Our findings that hs-CRP measured at one time point were associated with prostate cancer risk are supported by some studies, 7,17,24 but our results are also in contrast to others. 16,18,19,[21][22][23] In a nested case-control study including 622 prostate cancer cases, a positive association was observed between prediagnostic CRP and prostate cancer risk among men with BMI <25 kg/m 2 , even when CRP was measured several years before the diagnosis.…”

“…11,12 Furthermore, local inflammation has been observed in 35-100% of prostate cancer biopsies. 2,[13][14][15] Previous studies investigating the association between CRP and risk for prostate cancer development have shown conflicting results, as some studies found positive associations between level of inflammation-related biomarkers and risk of prostate cancer 7,16,17 ; others have not. [16][17][18][19][20][21][22][23][24] However, most studies have included only one single measurement of CRP, with a limited number of prostate cancer cases and short follow-up time.…”

“…2,[13][14][15] Previous studies investigating the association between CRP and risk for prostate cancer development have shown conflicting results, as some studies found positive associations between level of inflammation-related biomarkers and risk of prostate cancer 7,16,17 ; others have not. [16][17][18][19][20][21][22][23][24] However, most studies have included only one single measurement of CRP, with a limited number of prostate cancer cases and short follow-up time. 7,[16][17][18][19][20][21][22][23][24] The aim of the present study was to investigate associations between the inflammation-related biomarkers CRP and WBC and risk of prostate cancer development and severity.…”

“…[16][17][18][19][20][21][22][23][24] However, most studies have included only one single measurement of CRP, with a limited number of prostate cancer cases and short follow-up time. 7,[16][17][18][19][20][21][22][23][24] The aim of the present study was to investigate associations between the inflammation-related biomarkers CRP and WBC and risk of prostate cancer development and severity. A second aim is to determine whether markers of inflammation (WBC and high sensitivity-CRP, hs-CRP) independently or in combination were associated with risk and severity of prostate cancer, and to look at change in CRP and risk of prostate cancer development and severity.…”

Circulating inflammation markers and prostate cancer

“…A direct pro‐oncogenic effect of inflammatory signal molecules has, in addition to oxidative stress and perpetuated growth‐signaling, been proposed as a possible mechanism underlying the association between inflammation and cancer . Elevated prediagnostic markers of inflammation have been associated with prostate cancer severity, and a prediagnostic cytokine profile indicative of a type‐1 T helper cell‐shifted immune response has been observed to be inversely associated with prostate cancer risk …”