Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.
ABSTRACT Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status.
We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.
A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity.
UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma β-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC.
Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC.
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ABSTRACT: Abstract Aim: DNA methylation plays important roles in various kinds of carcinogenesis. Vitamin C could induce Tet-dependent DNA demethylation in embryonic stem cells. Therefore, the antagonizing activity of vitamin C on ultraviolet (UV)-induced apoptosis was investigated in this study. Methods: Apoptosis of human epidermoid carcinoma A431 cells and p16-knockout (KO) or p21-KO fibroblasts was assessed by a fluorescence-activated cell sorter. Real-time PCR and western blot were used to determine the relative expression levels of p12, p21, and Tet1/2/3 genes. The global DNA methylation levels were determined using MethylFlash Methylated DNA Quantification Kit in A431 cells with or without vitamin C treatment. To examine the DNA demethylation activity of vitamin C, DNA immunoprecipitation (DIP)-qPCR was performed to determine the relative levels of 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) in p16 and p21 promoter regions containing cytosine-phosphorothiolated guanine (CpG) islands. Results: The increasing apoptosis of A431 cells under prolonged UV irradiation was remarkably decreased by the combination of vitamin C treatment, suggesting that vitamin C protects against UV-induced apoptosis. Concurrently, vitamin C induced a significant reduction of global DNA methylation in a time- and dose-dependent manner in A431 cells. Vitamin C also reactivated the expression of p16 and p21 at mRNA and protein levels. Mechanistically, about 27% 5hmC-positive cells were observed in vitamin C-treated A431 cells, and the 5hmC enrichment at p16 and p21 promoter regions was also largely increased by vitamin C. Moreover, the expression of p16 and p21 was decreased in Tet1/2 double-knockdown cells, in which the inhibitory effect of vitamin C on UV-induced apoptosis was dismissed. Furthermore, the inhibition of UV-induced apoptosis on vitamin C treatment nearly disappeared in p16- or p21-knockout primary cultured fibroblasts. Conclusion: These results demonstrate that vitamin C effectively antagonizes UV-induced apoptosis through regulation of Tet activity, DNA demethylation, and subsequent tumor suppressor gene activation in skin cancer cells.Cancer Biotherapy and Radiopharmaceuticals 07/2014; · 1.38 Impact Factor
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ABSTRACT: Background:There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.Results:During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.Conclusions:Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.British Journal of Cancer advance online publication, 14 August 2014; doi:10.1038/bjc.2014.459 www.bjcancer.com.Cancer 08/2014; · 5.20 Impact Factor
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ABSTRACT: Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20-25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC.International Journal of Molecular Sciences 01/2013; 15(1):1433-40. · 2.34 Impact Factor