Dietary antioxidant supplements and risk of keratinocyte cancers in women: a prospective cohort study.

PURPOSE: Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk. METHODS: E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40-65 years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors. RESULTS: Over 1995-2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15-1.62), particularly with BCC (HR = 1.40, 95% CI 1.17-1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03-1.52) and SCC (HR = 1.43, 95% CI 1.03-1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00-2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake. CONCLUSIONS: Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed.

Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials.

Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22; P = 0.03, I2= 87.9%, P < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65; P = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54; P = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose-response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose-response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17-1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13-1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19-1.67), and 1.57 (0.64-3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk.

Patterns of Omega-3 and Omega-6 Fatty Acid Dietary Intake and Melanoma Thickness at Diagnosis.

BACKGROUND: Experimental evidence suggests that dietary intakes of omega-3 and omega-6 polyunsaturated fatty acids have divergent effects on melanoma growth, but epidemiologic evidence on their combined effect is lacking. METHODS: In 634 Australian patients with primary melanoma, we assessed prediagnosis consumption of 39 food groups by food frequency questionnaires completed within 2 months of diagnosis. We derived, by reduced rank regression, dietary patterns that explained variability in selected omega-3 and omega-6 fatty acid intakes. Prevalence ratios (PR) and 95% confidence intervals (CI) for the association between tertiles of dietary patterns and melanoma thickness >2 mm versus ≤2 mm were estimated using Poisson regression. RESULTS: Overall omega-3 fatty acid intakes were low. Two major fatty acid dietary patterns were identified: "meat, fish, and fat," positively correlated with intakes of all fatty acids; and "fish, low-meat, and low-fat," positively correlated with long-chain omega-3 fatty acid intake, and inversely with medium-chain omega-3 and omega-6 fatty acid intakes. Prevalence of thick melanomas was significantly higher in those in the highest compared with lowest tertile of the "meat, fish, and fat" pattern (PR, 1.40; 95% CI, 1.01-1.94), especially those with serious comorbidity (PR, 1.83; 95% CI, 1.15-2.92) or a family history (PR, 2.32; 95% CI, 1.00-5.35). The "fish, low-meat, and low-fat" pattern was not associated with melanoma thickness. CONCLUSIONS: People with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. IMPACT: High omega-3 and omega-6 fatty acid intakes may contribute to patients' presentation with thick melanomas.

A Metabolomic Study of Biomarkers of Habitual Coffee Intake in Four European Countries.

SCOPE: The goal of this work is to identify circulating biomarkers of habitual coffee intake using a metabolomic approach, and to investigate their associations with coffee intake in four European countries. METHODS AND RESULTS: Untargeted mass spectrometry-based metabolic profiling is performed on serum samples from 451 participants of the European Prospective Investigation on Cancer and Nutrition (EPIC) originating from France, Germany, Greece, and Italy. Eleven coffee metabolites are found to be associated with self-reported habitual coffee intake, including eight more strongly correlated (r = 0.25-0.51, p < 10E-07 ). Trigonelline shows the highest correlation, followed by caffeine, two caffeine metabolites (paraxanthine and 5-Acetylamino-6-amino-3-methyluracil), quinic acid, and three compounds derived from coffee roasting (cyclo(prolyl-valyl), cyclo(isoleucyl-prolyl), cyclo(leucyl-prolyl), and pyrocatechol sulfate). Differences in the magnitude of correlations are observed between countries, with trigonelline most highly correlated with coffee intake in France and Germany, quinic acid in Greece, and cyclo(isoleucyl-prolyl) in Italy. CONCLUSION: Several biomarkers of habitual coffee intake are identified. No unique biomarker is found to be optimal for all tested populations. Instead, optimal biomarkers are shown to depend on the population and on the type of coffee consumed. These biomarkers should help to further explore the role of coffee in disease risk.

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

Coffee and Tea Consumption and the Contribution of Their Added Ingredients to Total Energy and Nutrient Intakes in 10 European Countries: Benchmark Data from the Late 1990s.

BACKGROUND: Coffee and tea are among the most commonly consumed nonalcoholic beverages worldwide, but methodological differences in assessing intake often hamper comparisons across populations. We aimed to (i) describe coffee and tea intakes and (ii) assess their contribution to intakes of selected nutrients in adults across 10 European countries. METHOD: Between 1995 and 2000, a standardized 24-h dietary recall was conducted among 36,018 men and women from 27 European Prospective Investigation into Cancer and Nutrition (EPIC) study centres. Adjusted arithmetic means of intakes were estimated in grams (=volume) per day by sex and centre. Means of intake across centres were compared by sociodemographic characteristics and lifestyle factors. RESULTS: In women, the mean daily intake of coffee ranged from 94 g/day (~0.6 cups) in Greece to 781 g/day (~4.4 cups) in Aarhus (Denmark), and tea from 14 g/day (~0.1 cups) in Navarra (Spain) to 788 g/day (~4.3 cups) in the UK general population. Similar geographical patterns for mean daily intakes of both coffee and tea were observed in men. Current smokers as compared with those who reported never smoking tended to drink on average up to 500 g/day more coffee and tea combined, but with substantial variation across centres. Other individuals' characteristics such as educational attainment or age were less predictive. In all centres, coffee and tea contributed to less than 10% of the energy intake. The greatest contribution to total sugar intakes was observed in Southern European centres (up to ~20%). CONCLUSION: Coffee and tea intake and their contribution to energy and sugar intake differed greatly among European adults. Variation in consumption was mostly driven by geographical region.

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2 = 1.06, 95% CI 0.99-1.14) or in men (HRlog2 = 0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2 = 0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HRlog2 = 1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.