Smoking, hypertension, abdominal obesity and metabolic abnormalities have been considered individual factors involved in prostate cancer (PCa) pathogenesis. All of these factors are used to define ...the individual cardiovascular risk (CVR). The aim of our study was to evaluate the association between CVR and PCa diagnosis and grade among a consecutive series of men undergoing prostate biopsy.
From 2010 onwards, consecutive patients undergoing 12-core prostate biopsy were enrolled. Body mass index was measured before the biopsy. Blood samples were collected and tested for: PSA, fasting glucose, triglycerides and high-density lipoproteins. Blood pressure was also recorded. Metabolic syndrome was defined according to the Adult Treatment Panel III and CVR according to the European Association of Cardiologist Guidelines. We evaluated the association between CVR and PCa biopsy Gleason score using logistic regression analyses.
Five hundred and eighty-four patients were enrolled. Four hundred and six patients (70%) presented a moderate/high CVR. Two hundred and thirty-seven (40.6%) patients had cancer on biopsy; 157 with moderate/high CVR and 80 with low/no CVR (P=0.11). Out of the 237 patients with PCa, 113 had a Gleason score 6 and 124 a Gleason score ⩾7. Out of them, 92/124 (75%) presented a moderate/high CVR (P=0.004). Moderate/high CVR was not associated with an increased risk of PCa (odds ratio (OR): 0.741, confidence interval (CI): 0.474-1.156; P=0.186) but with an increased risk of Gleason score ⩾7 (OR: 2.154, CI: 1.076-4.314; P=0.030).
In our study, a moderate/high CVR is associated with an increased risk of a high-grade Gleason score when PCa is diagnosed on biopsy. Although these results should be confirmed in multicentre studies, patients with moderate/high CVR should be carefully evaluated for PCa diagnosis.
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype ...effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD45RO-; CD8CD45RO+ to CD8CD45RO-, NK CD56 dim to bright and monocyte numbers and percentages. Whole blood expression levels of IFNL3, IFNLR1 (interferon lambda receptor 1), IFNLR1-mem (a membrane-associated receptor), IFNLR1-sol (a truncated soluble receptor), MxA and T- and NK (natural killer) cell transcription factors TBX21, GATA3, RORC, FOXP3 and EOMES in two subjects were also determined. CHC patients demonstrated endogenous IFN activation with higher levels of MxA, IFNLR1, IFNLR1-mem and IFNLR1-sol, and IFNL3 genotype-associated differences in transcription factors. Taken together, these data provide evidence of an IFNL3 genotype association with differences in monocyte, T- and NK cell levels in the peripheral blood of patients with CHC. This could underpin genotype associations with spontaneous and treatment-induced HCV clearance and hepatic necroinflammation.
PDF
