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Long-term cancer survivors represent a sizeable portion of the population. Plant-based foods may enhance the prevention of cancer-related outcomes in these patients. We aimed to synthesize the current evidence regarding the impact of plant-based dietary patterns (PBDPs) on cancer-related outcomes in the general population and in cancer survivors. Considered outcomes included overall cancer mortality, cancer-specific mortality, and cancer recurrence. A rapid review was conducted, whereby 2234 original articles related to the topic were identified via Pubmed/Medline. We selected 26 articles, which were classified into studies on PBDPs and cancer outcomes at pre-diagnosis: vegan/vegetarian diet (N = 5), provegetarian diet (N = 2), Mediterranean diet (N = 13), and studies considering the same at post-diagnosis (N = 6). Pooled estimates of the associations between the aforementioned PBDPs and the different cancer outcomes were obtained by applying random effects meta-analysis. The few studies available on the vegetarian diet failed to support its prevention potential against overall cancer mortality when compared with a non-vegetarian diet (e.g., pooled hazard ratio (HR) = 0.97; 95% confidence interval (CI): 0.88–1.06). The insufficient number of studies evaluating provegetarian index scores in relation to cancer mortality did not permit a comprehensive assessment of this association. The association between adherence to the Mediterranean diet and cancer mortality reached statistical significance (e.g., pooled HR = 0.84; 95% CI: 0.79–0.89). However, no study considered the influence of prognostic factors on the associations. In contrast, post-diagnostic studies accounted for prognostic factors when assessing the chemoprevention potential of PBDPs, but also were inconclusive due to the limited number of studies on well-defined plant-based diets. Thus, whether plant-based diets before or after a cancer diagnosis prevent negative cancer-related outcomes needs to be researched further, in order to define dietary guidelines for cancer survivors.

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure 1 . The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion 2 , 3 . However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH) 4 – 8 . Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention. Individuals who are at high risk of developing acute myeloid leukaemia can be identified years before diagnosis using genetic information from blood samples.

Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM–10 µM). Oil Red staining was used to measure intracellular lipid accumulation, quantitative real-time polymerase chain reaction (qRT-PCR) to study gene expression of adipogenic markers (PPARγ, C/EBPα, LPL, and FABP4), and Western Blot to determine their corresponding proteins. The MIX promoted intracellular lipid accumulation in a dose-dependent manner with a maximal response at 10 µM. Co-incubation with pure antiestrogen (ICI 182,780) inhibited lipid accumulation, suggesting that the effect was mediated by the estrogen receptor. The MIX also significantly altered the expression of PPARγ, C/EBPα, LPL, and FABP4 markers, observing a non-monotonic (U-shaped) dose-response, with maximal gene expression at 10 nM and 10 µM and lesser expression at 1 µM. This pattern was not observed when bisphenols were tested individually. Exposure to MIX (1–10 µM) also increased all encoded proteins except for FABP4, which showed no changes. Evaluation of the combined effect of relevant chemical mixtures is needed rather than single chemical testing.

Diet may influence the development of inflammatory bowel disease through the modulation of inflammation. We investigated whether the inflammatory potential of the diet is associated with the risk of Crohn’s disease (CD) and ulcerative colitis (UC) in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The study included 32,633 participants aged 29–69 years. The inflammatory potential of the diet was measured by using an inflammatory score of the diet (ISD) based on a baseline dietary history questionnaire. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 21 years (674,547 person-years) of follow-up, 32 and 57 participants developed CD and UC, respectively. In multivariable analysis, a one-standard deviation (SD) increment in the ISD (two-unit increase) was associated with a higher risk of CD (HR of 1.71; 95% CI: 1.05–2.80; p = 0.031). By contrast, ISD was not associated with UC (HR for one-SD increment of 0.89; 95% CI: 0.66–1.19; p = 0.436). Our results suggest that consuming a more pro-inflammatory diet may contribute to the risk of CD, supporting that a healthy diet might be beneficial in its prevention. Further, larger studies are needed to verify these findings.

Background Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). Methods We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. Results Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 ( p  = 0.022), 37% increase for tertile 2 ( p  = 0.034) and 31% increase for tertile 3 ( p  = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. Conclusions We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk.

Despite regulatory actions, lead (Pb) exposure remains a major environmental health concern worldwide due to its widespread occurrence and potential adverse effects. The aims of this study were to explore internal Pb exposure in EU citizens, identify its main sociodemographic determinants, and investigate temporal variations over the last decades. Blood Pb data from a total of 17,790 individuals from 9 biomonitoring studies conducted between 2003 and 2019 in four European countries [Belgium (FLEHS I-IV), teenagers and adults; Czech Republic (SZU), children and adults; Spain (BIOAMBIENT.ES), adults; Germany (ESB, GerES IV and V), with all three age groups] were used. The European Human Biomonitoring Initiative (HBM4EU) harmonized and integrated the different datasets. Linear mixed-model analyses were performed to explore exposure determinants related to Pb concentrations. All participants showed detectable blood Pb concentrations, with an overall mean concentration (± standard deviation) of 20.6 (± 16.7) µg/L. In multivariable analyses, older age at recruitment, smoking habit and residence in more urbanized areas were associated with higher Pb levels, whereas more recent sampling year and higher educational level with lower concentrations. After pooled analysis of individual data, no significant differences were found in the Pb levels of the European citizens studied, probably due to the heterogeneity of the studies included. Collaborative efforts between public health agencies, environmental regulators and communities must continue to monitor trends, explore emerging sources of exposure and refine strategies to ensure sustained progress in reducing Pb levels and protecting the health of European population.

Colorectal cancer (CRC) is the most frequently diagnosed cancer in Spain. Socioeconomic inequalities in cancer survival are not documented in Spain. We aim to study the association of socioeconomic inequalities with overall mortality and survival among CRC patients in southern Spain. We conducted a multilevel population-based cohort study, including CRC cases for the period 2011-2013. The study time-to-event outcome was death, and the primary exposure was CRC patients' socioeconomic status assessed by the Spanish deprivation index at the census tract level. We used a mixed-effects flexible hazard model, including census tract as a random intercept, to derive overall survival estimates by deprivation. Among 3589 CRC patients and 12,148 person-years at risk (pyr), 964 patients died before the end of the follow-up. Mortality by deprivation showed the highest mortality rate for the most deprived group (96.2 per 1000 pyr, 95% CI: 84.0-110.2). After adjusting for sex, age, cancer stage, and the area of residence, the most deprived had a 60% higher excess mortality risk than the less deprived group (excess mortality risk ratio: 1.6, 95% CI: 1.1-2.3). We found a consistent association between deprivation and CRC excess mortality and survival. The reasons behind these inequalities need further investigation in order to improve equality cancer outcomes in all social groups.

PurposeThyroid cancer (TC) is the most common malignant disease of the endocrine system. The aim of this study was to analyze incidence and mortality trends of TC (C73 according to ICD-O-3) in Granada (Southern Spain) during the period 1985–2013, by sex, age, and histological type.MethodsThis is a population-based cross-sectional study. Incidence data were obtained from the population-based Cancer Registry of Granada. All newly diagnosed cases of thyroid cancer over the period 1985–2013 were included. Joinpoint regression analysis with age-standardized rates were used to estimate annual percentage change (APC), CI 95% and turning points in trends. Results are presented by sex, age group, and histological type.ResultsDuring the study period there were 1265 diagnosed cases of TC in Granada (72.6% in women). Incidence trends significantly increased in both men (APC: + 5.4%) and women (APC: + 4.7%). The most common histological types in both sexes were papillary (74.8%) and follicular (16.8%). The incidence has increased during the study period mainly due to papillary carcinoma, which has increased annually around 6% in both sexes. TC mortality trend during this period decreased in men (APC: −0.3%) and women (APC: −2.3%).ConclusionOur data showed an increasing trend in incidence of thyroid cancer in Granada, especially in women between 55–64 years. Mortality showed a slight decrease trend during the study period in both sexes. Papillary carcinoma was the most common histological type, with an increase of the relative weight of papillary microcarcinomas. Our study is in accordance with the European and worldwide trends in thyroid cancer incidence and mortality and sex differences.

Brain-derived neurotrophic factor (BDNF), a neurotrophic growth factor mainly expressed in the brain, has been proposed as a potential effect biomarker; that is, as a measurable biomarker whose values could be associated with several diseases, including neurological impairments. The European Human Biomonitoring Initiative (HBM4EU) has also recognized effect biomarkers as a useful tool for establishing link between exposure to environmental pollutants and human health. Despite the well-establish protocol for measuring serum BDNF, there is a need to validate its assessment in urine, a non-invasive sample that can be easily repeated over time. The aim of this study was to develop, standardize and validate a methodology to quantify BDNF protein levels in urine samples before its implementation in biomonitoring studies. Different experimental conditions and non-competitive commercial enzyme-linked immunosorbent assay (ELISA) kits were tested to determine the optimal analytical procedure, trying to minimize the shortcomings of ELISA kits. The fine-tune protocol was validated in a pilot study using both upon awakening (  = 150) and prior to sleeping (  = 106) urine samples from the same Spanish adolescent males in a well-characterized study population (the Spanish INMA-Granada cohort). The best results were obtained in 0.6 ml of urine after the acidification and extraction (pre-concentration) of samples. The highest reproducibility was obtained with the ELISA kit from Raybiotech. Urinary BDNF concentrations of adolescent males were within the previously reported range (morning = 0.047-6.801 ng/ml and night = 0.047-7.404 ng/ml). Urinary BDNF levels in the awakening and pre-sleep samples did not follow a normal distribution and were not correlated. The developed methodology offers good sensitivity and reproducibility. Having reliable markers in urine may facilitate both diagnosis and monitoring possible diseases (and treatment). Further studies are needed to implement urinary BDNF in biomonitoring studies to further elucidate its usefulness and biological significance for neurological impairments.

Zheng, J.-S., Imamura, F., Sharp, S.J., Van Der Schouw, Y.T., Sluijs, I., Gundersen, T.E., Ardanaz, E., Boeing, H., Bonet, C., Gómez, J.H., Dow, C., Fagherazzi, G., Franks, P.W., Jenab, M., Kuhn, T., Kaaks, R., Key, T.J., Khaw, K.-T., Lasheras, C., Mokoroa, O., Mancini, F.R., Nilsson, P.M., Overvad, K., Panico, S., Palli, D., Rolandsson, O., Sieri, S., Salamanca-Fernández, E., Sacerdote, C., Spijkerman, A.M.W., Stepien, M., Tjonneland, A., Tumino, R., Butterworth, A.S., Riboli, E., Danesh, J., Langenberg, C., Forouhi, N.G., Wareham, N.J.