Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Radiation-Induced Cerebro-Ophthalmic Effectsin Humans

: Exposure to ionizing radiation (IR) could affect the human brain and eyes leading to both cognitive and visual impairments. The aim of this paper was to review and analyze the current literature, and to comment on the ensuing findings in the light of our personal contributions in this field. The review was carried out according to the PRISMA guidelines by searching PubMed, Scopus, Embase, PsycINFO and Google Scholar English papers published from January 2000 to January 2020. The results showed that prenatally or childhood-exposed individuals are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. In adulthood and medical/interventional radiologists, the most frequent IR-induced ophthalmic effects include cataracts, glaucoma, optic neuropathy, retinopathy and angiopathy, sometimes associated with specific neurocognitive deficits. According to available information that eye alterations may induce or may be associated with brain dysfunctions and vice versa, we propose to label this relationship “eye-brain axis”, as well as to deepen the diagnosis of eye pathologies as early and easily obtainable markers of possible low dose IR-induced brain damage

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT: PART II – RADIATION CEREBRO-OPHTALMIC EFFECTS IN CHILDREN, PERSONS EXPOSED IN UTERO, ASTRONAUTS AND INTERVENTIONAL RADIOLOGISTS

Background. Ionizing radiation (IR) can affect the brain and the visual organ even at low doses, while provoking cognitive, emotional, behavioral, and visual disorders. We proposed to consider the brain and the visual organ as potential targets for the influence of IR with the definition of cerebro-ophthalmic relationships as the «eye-brain axis». Objective. The present work is a narrative review of current experimental, epidemiological and clinical data on radiation cerebro-ophthalmic effects in children, individuals exposed in utero, astronauts and interventional radiologists. Materials and methods. The review was performed according to PRISMA guidelines by searching the abstract and scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, Google Scholar, published from 1998 to 2021, as well as the results of manual search of peer-reviewed publications. Results. Epidemiological data on the effects of low doses of IR on neurodevelopment are quite contradictory, while data on clinical, neuropsychological and neurophysiological on cognitive and cerebral disorders, especially in the left, dominant hemisphere of the brain, are nore consistent. Cataracts (congenital – after in utero irradiation) and retinal angiopathy are more common in prenatally-exposed people and children. Astronauts, who carry out longterm space missions outside the protection of the Earth's magnetosphere, will be exposed to galactic cosmic radiation (heavy ions, protons), which leads to cerebro-ophthalmic disorders, primarily cognitive and behavioral disorders and cataracts. Interventional radiologists are a special risk group for cerebro-ophthalmic pathology – cognitive deficits, mainly due to dysfunction of the dominant and more radiosensitive left hemisphere of the brain, and cataracts, as well as early atherosclerosis and accelerated aging. Conclusions. Results of current studies indicate the high radiosensitivity of the brain and eye in different contingents of irradiated persons. Further research is needed to clarify the nature of cerebro-ophthalmic disorders in different exposure scenarios, to determine the molecular biological mechanisms of these disorders, reliable dosimetric support and taking into account the influence of non-radiation risk factors. Key words: ionizing radiation, brain, eye, cerebro-ophthalmic effects, radiation emergencies, prenatal irradiation, space flights, interventional radiology

Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study

Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HR) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% (HR: 0.28; 95% confidence intervals (CI): 0.16 to 0.50, P-trend <0.001). The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22 to 0.78, P-trend=0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (P-trend=0.009), but not decaffeinated (P-trend=0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multi-centre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects

Serum endotoxins and flagellin and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. Methods: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18). Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. Impact: Further studies are warranted to better clarify these preliminary observations

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK)

Prediagnostic concentrations of plasma genistein and prostate cancer risk in 1,605 men with prostate cancer and 1,697 matched control participants in EPIC

PURPOSE: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of genistein were estimated by conditional logistic regression. RESULTS: Plasma genistein concentrations were not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of genistein compared with men in the lowest fifth was 1.00 (95 % confidence interval: 0.79, 1.27; p linear trend = 0.82). There was no evidence of heterogeneity in this association by age at blood collection, country of recruitment, or cancer stage or histological grade. CONCLUSION: Plasma genistein concentration was not associated with prostate cancer risk in this large cohort of European men

Smoking, Alcohol, Diabetes, Obesity, Socioeconomic Status, and the Risk of Colorectal Cancer in a Population-Based Case–Control Study

Purpose: Although previous research has identified factors that may determine willingness to participate in research, relatively few studies have attempted to quantify the impact non-participation may have on exposure–disease associations. The aims of this study were to (a) investigate the associations between smoking, alcohol, diabetes, obesity, and socioeconomic status and the risk of colorectal cancer in a case–control study (59.7 and 47.2 % response fractions among cases and controls, respectively); and (b) perform sensitivity analyses to examine the possible influence of non-participation. Methods: Logistic regression was used to estimate the exposure–disease associations. We then investigated the associations between various demographic and health factors and the likelihood that an individual would participate in the case–control study and then performed two sensitivity analyses (sampling weights and multiple imputation) to examine whether non-participation bias may have influenced the exposure–disease associations. Results: The exposures alcohol, smoking, and diabetes were associated with an increased risk of colorectal cancer. We found some differences between cases and controls when examining the factors associated with the participation in the study, and in the sensitivity analyses, the exposure–disease associations were slightly attenuated when compared with those from the original analysis. Conclusion: Non-participation may have biased the risk estimates away from the null, but generally not enough to change the conclusions of the study