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.
Highlights
Flavonoid phytoestrogens are bioactive, polyphenolic compounds found in plant-based food and share common chemical structural characteristics with endogenous estrogen
Of the 2051 patients diagnosed with stage of I to III colorectal cancer, serum genistein concentration was detected in 2029 participants, and luteolin concentration in 2011 participants
There were no significant differences across quartiles of either genistein or luteolin concentration according to gender, stage, colorectal cancer (CRC) sites, grade, BMI, education, tumor detection mode, and adjuvant chemotherapy
Summary
Polyphenolic compounds found in plant-based food and share common chemical structural characteristics with endogenous estrogen. Absorption occurs in both the small and large intestines, with a large portion of flavonoid metabolites reaching the colon [3]. Due to the limited surface for absorption in the colon, the absorption rate is very low and the urinary excretion rate of flavonoid subclasses ranges from 0.3–20% [4,5]. Both low oral bioavailability and low correlation between dietary intake and serum biomarker concentration have been observed in intervention studies [6,7]
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