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Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis.

ABSTRACT: Although flavonoid phytoestrogens have been suggested to be associated with reduced risk of colorectal cancer (CRC), their influence on CRC prognosis remains uncertain. A population-based cohort of 2051 patients diagnosed with stage I?III CRC in southwest Germany in 2003?2010 were followed for five years. Post-diagnostic serum concentration of genistein and luteolin were measured using Ultra-Performance Liquid Chromatography with mass spectrometry. Multivariable Cox regression analysis was conducted to calculate the Hazard Ratios (HRs) and 95% confidence interval (CI) for the association between flavonoids concentration and overall morality, CRC-specific mortality, CRC recurrence, and disease-free survival (DFS). Median (interquartile range) serum concentration of genistein and luteolin was 11.90 ng/µL (10.08?14.13) and 7.20 ng/µL (6.40?8.16), respectively. Neither serum genistein nor luteolin was associated with CRC prognosis. There was no clear evidence of departure from linearity. However, the association might be differential by adjuvant chemotherapy. Associations pointed towards lower risk in patients who received chemotherapy and higher risk in those without chemotherapy for overall mortality regarding serum genistein (P-interaction = 0.02) and correspondingly for CRC recurrence (P-interaction: 0.03) and DFS (P-interaction: 0.01) with respect to luteolin. Our study provides little evidence that serum genistein and luteolin are associated with colorectal cancer prognosis. Future studies are warranted to evaluate the potential interaction with adjuvant chemotherapy.

SUBMITTER: Jiang R

PROVIDER: S-EPMC6472030 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis.

Jiang Ruijingfang R Poschet Gernot G Owen Robert R Celik Muhabbet M Jansen Lina L Hell Rüdiger R Hoffmeister Michael M Brenner Hermann H Chang-Claude Jenny J

Nutrients 20190312 3

Although flavonoid phytoestrogens have been suggested to be associated with reduced risk of colorectal cancer (CRC), their influence on CRC prognosis remains uncertain. A population-based cohort of 2051 patients diagnosed with stage I⁻III CRC in southwest Germany in 2003⁻2010 were followed for five years. Post-diagnostic serum concentration of genistein and luteolin were measured using Ultra-Performance Liquid Chromatography with mass spectrometry. Multivariable Cox regression analysis was condu ...[more]

PMID: 30871032

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Project description:Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, -?9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation.We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998-2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test.Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17-2.52, P?=?0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23-2.64, P?=?0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33-0.98, P?=?0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS?=?0.229, P?<?0.001), and TIMP-1 (rS?=?0.280, P?<?0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10-2.53, P?=?0.017) and TIMP-1 (HR 1.59, 95% CI 1.05-2.42, P?=?0.029) were prognostic factors.MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis.

Dataset Information

Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis.

Publications

Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis.

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