Vitamin D Intake and the Risk of Colorectal Cancer: An Updated Meta-Analysis and Systematic Review of Case-Control and Prospective Cohort Studies

Obesity, a sedentary lifestyle, high red meat consumption and alcohol, and tobacco are considered the driving factors behind colorectal cancer (CRC) worldwide. Both diet and lifestyle are recognized to play an important role in the prevention of CRC. Forty years later, the vitamin D-cancer hypothesis is considered consistent. However, the relationship between low vitamin D intake and CRC is still controversial. The aim of this meta-analysis is to determine the associations between Vitamin D intake and CRC. MEDLINE-PubMed and Cochrane databases were searched up to May 2020 for studies evaluating the association between vitamin D intake (from foods and supplements) and CRC. Two reviewers, working independently, screened all titles and abstracts to identify the studies that met the inclusion criteria (case-control or prospective cohort (PC) studies published in English). Data were pooled by the generic inverse variance method using a random or fixed effect model. Heterogeneity was identified using the Cochran Q-test and quantified by the I2 statistic. A total of 31 original studies were included for the quantitative meta-analysis, comprising a total 47.540 cases and 70.567 controls in case-control studies, and a total of 14.676 CRC-incident cases (out of 808.130 subjects in PC studies) from 17 countries. A significant 25% lower risk was reported comparing the highest vs. the lowest dietary vitamin D consumption and CRC risk (odds ratio (95% confidence interval): 0.75 (0.67; 0.85)) in case-control studies, whereas a non-significant association was reported in case of prospective studies (hazard ratio (95% confidence interval): 0.94 (0.79; 1.11). The present meta-analysis demonstrates that high dietary vitamin D is associated to CRC prevention. However, larger and high-quality prospective studies and clinical trials are warranted to confirm this association. View Full-Text Keywords: vitamin D intake; meta-analysis; systematic review; colorectal cancer; incidence; case-control; prospectiv

Snail1 transcription factor controls telomere transcription and integrity

Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres. Remarkably, Snail1-deficient MSC present higher levels of both telomerase activity and the long non-coding RNA called telomeric repeat-containing RNA (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q, 11q and 18q. TERRA and TERT are transiently downregulated during TGF-induced EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome analysis indicates that ectopic expression of TERRA affects the transcription of some genes induced during EMT, such as fibronectin, whereas that of TERT does not modify those genes. We propose that Snail1 repression of TERRA is required not only for telomere maintenance but also for the expression of a subset of mesenchymal genes

Modulation of telomere length by Mediterranean diet, caloric restriction and exercise: Results from PREDIMED-Plus study

Telomere length (TL) has been associated with aging and is determined by lifestyle. However, the mechanisms by which a dietary pattern such as the Mediterranean diet (MedDiet) affects TL homeostasis are still unknown. Our aim was to analyse the effect of an energy-restricted MedDiet with physical activity promotion (intervention group) versus an unrestricted-caloric MedDiet with no weight-loss advice (control group) on TL and 8-hydroxydeoxyguanosine (8-OHdG) plasma levels. In total, 80 non-diabetic participants with metabolic syndrome were randomly selected from the PREDIMED (PREvención con DIeta MEDiterránea)-Plus-Reus study. TL was measured by a hybridisation method and 8-OHdG levels by ELISA at baseline and after one year of intervention. Linear mixed models (LMM) raw and after adjusting for potential confounders were used to examine the associations between TL or 8-OHdG plasma levels by intervention group and/or time. A total of 69 subjects with available DNA samples were included in the analyses. A significant β-coefficient was found for time towards increasing values through the year of follow-up for TL (unadjusted β of 0.740 (95% CI: 0.529 to 0.951), and multivariable model β of 0.700 (95% CI: 0.477 to 0.922)). No significant βs were found, neither for the intervention group nor for the interaction between the intervention group and time. Regarding 8-OHdG plasma levels, no significant βs were found for the intervention group, time, and its interaction. Our results suggest that MedDiet could have an important role in preventing telomere shortening, but calorie restriction and exercise promotion did not provide an additional advantage concerning telomere length after one year of MedDiet intervention

Snail1 transcription factor controls telomere transcription and integrity

Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres. Remarkably, Snail1-deficient MSC present higher levels of both telomerase activity and the long non-coding RNA called telomeric repeat-containing RNA (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q, 11q and 18q. TERRA and TERT are transiently downregulated during TGFβ-induced EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome analysis indicates that ectopic expression of TERRA affects the transcription of some genes induced during EMT, such as fibronectin, whereas that of TERT does not modify those genes. We propose that Snail1 repression of TERRA is required not only for telomere maintenance but also for the expression of a subset of mesenchymal genes

Snail1 transcription factor controls telomere transcription and integrity

Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres. Remarkably, Snail1-deficient MSC present higher levels of both telomerase activity and the long non-coding RNA called telomeric repeat-containing RNA (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q, 11q and 18q. TERRA and TERT are transiently downregulated during TGFβ-induced EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome analysis indicates that ectopic expression of TERRA affects the transcription of some genes induced during EMT, such as fibronectin, whereas that of TERT does not modify those genes. We propose that Snail1 repression of TERRA is required not only for telomere maintenance but also for the expression of a subset of mesenchymal genes

Extra virgin olive oil consumption reduces the risk of osteoporotic fractures in the PREDIMED trial

BACKGROUND & AIMS: The incidence of osteoporotic fractures is lower in countries in the Mediterranean basin. Virgin olive oil, a key component of the Mediterranean Diet (MDiet), with recognised beneficial effects on metabolism and cardiovascular health, may decrease the risk of osteoporotic fractures. The aim to this study was to explore the effect of chronic consumption of total olive oil and its varieties on the risk of osteoporosis-related fractures in a middle-aged and elderly Mediterranean population. METHODS: We included all participants (n = 870) recruited in the Reus (Spain) centre of the PREvención con DIeta MEDiterránea (PREDIMED) trial. Individuals, aged 55-80 years at high cardiovascular risk, were randomized to a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or a low-fat diet. The present analysis was an observational cohort study nested in the trial. A validated food frequency questionnaire was used to assess dietary habits and olive oil consumption. Information on total osteoporotic fractures was obtained from a systematic review of medical records. The association between yearly repeated measurements of olive oil consumption and fracture risk was assessed by multivariate Cox proportional hazards. RESULTS: We documented 114 incident cases of osteoporosis-related fractures during a median follow-up of 8.9 years. Treatment allocation had no effect on fracture risk. Participants in the highest tertile of extra-virgin olive oil consumption had a 51% lower risk of fractures (HR:0.49; 95% CI:0.29-0.81. P for trend = 0.004) compared to those in the lowest tertile after adjusting for potential confounders. Total and common olive oil consumption was not associated with fracture risk. CONCLUSIONS: Higher consumption of extra-virgin olive oil is associated with a lower risk of osteoporosis-related fractures in middle-aged and elderly Mediterranean population at high cardiovascular risk

Cancer signaling transcriptome is upregulated in type 2 diabetes mellitus

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini-Hochberg-adjusted p-value were >1.30 and their absolute z-scores were >2.0 (≥2.0 meant "upregulation" and ≤ -2.0 "downregulation"). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, -log(p-value) = 32.3; 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, -log(p-value) = 2.03) and paxillin (z-score = 2.33, -log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = -2.14, -log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation

Baseline drinking water consumption and changes in body weight and waist circumference at 2-years of follow-up in a senior Mediterranean population

The PREDIMEDPlus trial was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigacion para la Salud (FIS) and cofunded by European Union ERDF/ESF, "A way to make Europe"/"Investing in your future" (five coordinated FIS projects led by JS-S and JVid, including the following: PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/00728, PI14/01722, PI14/00636, PI14/01206, PI14/01919, PI14/01374, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00366, PI17/00764, PI17/01827, PI17/01441, PI17/01732, PI17/00926, PI19/00309, PI19/01032, PI19/00576, PI19/00017, and PI19/00781) , the Special Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to JSS, the European Research Council (Advanced Research Grant 2013-2018, 340918) to MAMG, the Recercaixa Grant to JS-S (2013ACUP00194) , a grant from the Generalitat Valenciana (PROMETEO/2017/017) , a SEMER-GEN grant, and funds from the European Regional Development Fund (CB06/03) . Study resulting from the SLT006/17/00246 grant, funded by the Department of Health of the Generalitat de Catalunya by the call "Accio instrumental de programes de recerca orientats en l'ambit de la recerca i la innovacio en salut". We thank the CERCA Programme/Generalitat de Catalunya for institutional support. This publication has been possible with the support of the Ministerio de Ciencia, Innovacion y Universidades (MICINN) (FPU 17/01925) . Jordi SalasSalvado, senior author of this study, is partially supported by ICREA under the ICREA Academia programme. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU 17/01925) . Dr. NB-T is supported by a postdoctoral fellowship (Juan de la Cierva-Formacion, FJC2018-036016-I) . I.M GimenezAlba received an FPU grant from the Ministry of Science, Innovation and Universities (reference FPU 18/01703) . C.B. received a Fernando Tarongi Bauza PhD Grant.Background & aims: The association between drinking water consumption and adiposity has been poorly explored. Therefore, we aimed to analyse the associations between the frequency of drinking water consumption and body weight and waist circumference changes in an elderly Mediterranean cohort. Methods: A total of 1832 elderly participants (aged 55e75 years) with metabolic syndrome from the PREDIMED-Plus study with baseline data on drinking water and other beverages assessed by a validated 32-item Spanish fluid-intake questionnaire and with data on body weight (BW) and waist circumference (WC) at 1-year and 2-year were included in these prospective analyses. Multivariable linear regression models were fitted to assess the b-coefficients and 95% confidence interval (CI) for BWand WC changes in terms of categories of baseline drinking water consumption (tap water and bottled water). The theoretical effect on BWand WC of replacing several beverages with drinking water was assessed using mathematical models. Results: The baseline frequency of drinking water consumptionwas inversely associated with 1-year and 2- year changes in BW. b-coefficients (95%CI) across categories ofwater consumption (<2.5, 2.5 to <5, 5 to < 7.5, 7.5 servings/d) expressed in % of weight changes at 2 years of follow-up were 0.0, 0.80 ( 1.48, 0.12), 1.36 ( 2.18, 0.54), and 1.97 ( 3.09, 0.86), respectively. Individuals in the two highest categories of drinkingwater consumption (5 to < 7, and 7.5 servings/d) also showed a higher decrease inWC (expressed as % of change) after 2 years of follow-up: 1.11 ( 1.96, 0.25) and 1.45 ( 2.66, 0.24) compared to the reference intake (<2.5 servings/day), after adjustment for potential confounding factors. The theoretical replacement of soups, beers, spirits, hot beverages, dairy beverages, and other beverages group with drinking water was associated with greater reductions in BWat one- and two-years of follow-up. Conclusions: Drinking water consumption was inversely associated with 2-year adiposity changes in an elderly Mediterranean cohort at high cardiovascular risk. Our results also suggest that the consumption of drinking water instead of energy-containing beverages is associated with lower weight gain.Spanish Government European CommissionEuropean Union ERDF/ESF, "A way to make Europe"/"Investing in your future" PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/00728 PI14/01722 PI14/00636 PI14/01206 PI14/01919 PI14/01374 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00366Special Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grantEuropean Research Council (ERC)European Commission 340918Recercaixa Grant 2013ACUP00194Generalitat Valenciana European Commission PROMETEO/2017/017SEMER-GEN grant European Commission CB06/03Department of Health of the Generalitat de Catalunya SLT006/17/00246Ministerio de Ciencia, Innovacion y Universidades (MICINN) FPU 17/01925ICREA under the ICREA Academia programmeSpanish Ministry of Education, Culture and Sports FPU 17/01925Juan de la Cierva-Formacion FJC2018-036016-IMinistry of Science, Innovation and Universities FPU 18/01703Fernando Tarongi Bauza PhD GrantThe European Union ERDF/ESF, "A way to make Europe"/"Investing in your future" PI17/00764 PI17/01827 PI17/01441 PI17/01732 PI17/00926 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/0078