Racial differences in serum chemokines in prostate cancer patients

Abstract

BackgroundThis study aimed to understand the differential levels of inflammatory chemokines in association with higher prostate cancer incidence and mortality in African American (AA) men than in Caucasians (CA).MethodsThe authors used a chemokine assay to simultaneously measure 40 chemokines and cytokines levels in the serum of preoperative prostate cancer patients and healthy controls of AA and CA races. Selected chemokines (CXCL2, CXCL5, and CCL23) serum level was validated in 211 serum samples from prostate cancer patients and healthy controls. Differential expression of CXCL5 and CCL23 was analyzed using immunohistochemistry in a representative cohort of prostate tumor tissues of AA and CA races.ResultsRace‐specific comparisons from 211 serum samples showed significantly higher levels of CXCL2 (control: 3104.0 pg/mL vs. cancer: 2451.0 pg/mL) and CXCL5 (control: 5189.0 pg/mL vs. cancer: 5459.0 pg/mL) in AA men than in CAs (CXCL2; control: 1155.0 pg/mL vs. cancer: 889.3 pg/mL, and CXCL5; control: 1183.0 pg/mL vs. cancer: 977.5 pg/mL). CCL23 differed significantly within and between the races with a lower level in AA cancer cases (454.5 vs. 966.6 pg/mL) than healthy controls (740.5 vs. 1263.0 pg/mL). Patient age, prostate‐specific antigen, or Gleason scores were not significantly associated with these chemokines. Immunostaining for CXCL5 and CCL23 in a representative cohort of archival prostate tissues displayed significantly higher CXCL5 in prostate tumors than in adjacent benign tissues, whereas CCL23 was nondetectable in most of the analyzed tumor tissues.ConclusionLower levels of CCL23 in AA prostate cancer patient sera and tumor tissues and high CXCL2 and CXCL5 may contribute to aggressive prostate cancer, as often seen in AA men. The disproportionate levels of serum chemokines associated with race warrant further exploration to improve equitability in precision oncology to benefit prostate cancer patients.

Contextualizing racial associations in prostate cancer to expose structural causes

“…the results, the authors do not mention racism or structural forces that are known to be the primary drivers of prostate cancer inequities, [2][3][4][5][6] and instead they propose genetic mechanisms of racial difference. 1 Biomedical research must start from the fact that race is a social construct: Racial categories are not a scientific way to describe genetic differences. Self-identified racial categories such as African American describe heterogenous groups of people with varying lived experiences and social and environmental exposures.…”

“…7,8 In their article, the authors describe racial inequities in prostate cancer and mention unequal access to care as a possible mechanism, but they then claim that "even after adjusting for nonbiological factors, prostate cancer mortality rates remain significantly higher" in African American men versus White men. 1 Because this statement could imply that nonbiological factors were all accounted for, it may be more appropriate to state that after adjustments for some nonbiological factors, inequities remain; this would better acknowledge the possibility of unmeasured confounders. The statement in the article also suggests that in contrast to nonbiological factors, race is somehow a biological factor rather than a social construct.…”

“…We also note that despite focusing on racial differences, this article does not use the word racism. 1 The article's finding would be better contextualized by referencing studies that have demonstrated how inequities in environmental exposures, discrimination, racism, poverty, and "toxic stress" lead to prostate cancer inequities. [2][3][4][5][6]9,10 Because of the strong published evidence for the role of structural racism in the racial inequities in prostate cancer outcomes, not mentioning racism and instead discussing genetic differences in the allelic frequency of Duffy antigen receptor for chemokines (DARC) could lead readers to misattribute the cause of prostate cancer inequities to some inherent genetic difference between socially constructed racial groups.…”

“…11,12 The described racial differences in serum levels of CXCL2, CXCL2, and CCL23 could help to guide new therapeutic targets and help patients who are suffering from prostate cancer. 1 Moreover, if these serum cytokines are associated with prostate cancer outcomes, they could help to better elucidate biological pathways of disease.…”