Explore the vast range of titles available.

Background Intake of lycopene has been proposed as a protective dietary factor against prostate cancer development. Cardiovascular disease and prostate cancer share risk factors, which may modulate the effect of lycopene in high-risk individuals. This study aimed to examine the association between lycopene intake and prostate cancer risk in a Mediterranean population at high cardiovascular risk. Methods A prospective cohort analysis was conducted among 2970 men aged 55–80 years at high cardiovascular risk from the PREDIMED trial, a multicenter study in Spain. Lycopene intake was assessed using repeated food frequency questionnaires. Prostate cancer cases were identified through medical records and death certificates. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) across lycopene intake quartiles. Results Over a mean follow-up of 5.8 years, 104 prostate cancer cases were identified. Participants in the highest quartile of lycopene intake had a significantly lower risk of prostate cancer than those in the lowest quartile (HR: 0.46; 95% CI: 0.23–0.95; p -trend = 0.035). A nonlinear dose–response relationship was observed, with a significant inverse association emerging at intakes above 4.9 mg/day (HR: 0.36; 95% CI: 0.13–0.98). Conclusions Higher lycopene intake suggested a protective association with a lower incidence of prostate cancer in men at high cardiovascular risk. These findings support the role of lycopene-rich diets in prostate cancer prevention, which may be particularly relevant for high cardiovascular risk populations. Trial registration ISRCTN registry: ISRCTN35739639 (PREDIMED trial).

Precision nutrition aims to make dietary recommendations of a more personalized nature possible, to optimize the prevention or delay of a disease and to improve health. Therefore, the characteristics (including sex) of an individual have to be taken into account as well as a series of omics markers. The results of nutritional genomics studies are crucial to generate the evidence needed so that precision nutrition can be applied. Although sex is one of the fundamental variables for making recommendations, at present, the nutritional genomics studies undertaken have not analyzed, systematically and with a gender perspective, the heterogeneity/homogeneity in gene-diet interactions on the different phenotypes studied, thus there is little information available on this issue and needs to be improved. Here we argue for the need to incorporate the gender perspective in nutritional genomics studies, present the general context, analyze the differences between sex and gender, as well as the limitations to measuring them and to detecting specific sex-gene or sex-phenotype associations, both at the specific gene level or in genome-wide-association studies. We analyzed the main sex-specific gene-diet interactions published to date and their main limitations and present guidelines with recommendations to be followed when undertaking new nutritional genomics studies incorporating the gender perspective.

There is adherence to a healthy Mediterranean diet (MedDiet), but adherence varies widely. Precision nutrition is increasingly interested in individual characteristics influencing diet adherence, but few studies have examined personality traits. Our main aim was to investigate the association between personality traits and MedDiet adherence. Our secondary aims were to explore genome-wide genetic variants associated with neuroticism, including replication of previous findings, as well as to explore gene-MedDiet interactions. We analyzed participants (aged 55-75) in the PREDIMED-Plus-Valencia study and measured clinical, lifestyle, and genetic factors. The Eysenck Personality Questionnaire-Revised (EPQ-R) was used to measure neuroticism, psychoticism, and extraversion. Genotyping was undertaken, and associations with candidate SNPs, genome-wide association studies (GWAS), genetic risk scores (GRS), and gene-MedDiet interactions were explored. Neuroticism was inversely (beta = -0.09; = 0.001) associated with adherence to the Mediterranean diet (MEDAS-17). Likewise, the probability of low MedDiet adherence increased neuroticism (OR: 1.27; 95% CI: 1.02-1.60; = 0.031 per SD). In the GWAS for this trait, several SNPs surpassed the suggestive level of statistical significance. The most strongly associated was rs10181407- (NADH dehydrogenase 1 alpha subcomplex subunit 10) (beta = -2.39; = 2.70 × 10 ). The GRS for neuroticism was significantly associated with MedDiet adherence (beta = -0.18; = 0.020), increasing the causality level. We replicated some candidate SNPs, and among them, the rs2243873- (euchromatic histone lysine methyltransferase 2) gene. The analysis of gene-MedDiet interactions revealed the role of these dietary modulations. Neuroticism was the personality trait most inversely associated with MedDiet adherence, suggesting its integration in precision nutrition analysis. Moreover, neuroticism-related genetics and MedDiet modulations will also be important.

Purpose We evaluated whether the intake of dietary vitamin D is associated with the incidence of both colorectal cancer (CRC) and colon cancer in the framework of the PREDIMED cohort of older adults at high cardiovascular risk. Methods We analyzed data from 7216 men and women (55–80 years) without CRC at baseline from the PREvención con DIeta MEDiterránea study. Baseline consumption of vitamin D was assessed using a validated 137-item food frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC and colon cancer incidence were estimated for quartiles and per 1-SD of baseline vitamin D intake. Results During a median follow-up of 6 years, we documented 97 incident CRC cases after the exclusion of subjects with no baseline dietary data and/or outliers of energy intake. A non-significant HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme quartiles (4th vs 1st) of vitamin D intake were observed [0.55 (0.30–1.00), P for trend = 0.072], whereas it was significant for colon cancer incidence alone [0.44 (0.22–0.90), P for trend = 0.032]. However, this association became significant in CRC and colon cancer incidence, after excluding 391 subjects consuming baseline vitamin D and/or calcium medication or prescribed supplements [0.52 (0.28–0.96) and 0.41 (0.12–0.85), respectively]. Conclusion A higher dietary intake of vitamin D was significantly associated with a reduced CRC risk in individuals at high cardiovascular risk.

Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the FADS cluster and omega-3 concentrations (top-ranked in the adjusted model: FADS1-rs174547, p = 3.34 × 10−14; FADS1-rs174550, p = 5.35 × 10−14; FADS2-rs1535, p = 5.85 × 10−14; FADS1-rs174546, p = 6.72 × 10−14; FADS2-rs174546, p = 9.75 × 10−14; FADS2-rs174576, p = 1.17 × 10−13; FADS2-rs174577, p = 1.12 × 10−12, among others). We also detected a genome-wide significant association with other genes in chromosome 11: MYRF (myelin regulatory factor)-rs174535, p = 1.49 × 10−12; TMEM258 (transmembrane protein 258)-rs102275, p = 2.43 × 10−12; FEN1 (flap structure-specific endonuclease 1)-rs174538, p = 1.96 × 10−11). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the DNTTIP2 (deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965 p = 1.36 × 10−8. For adherence to MedDiet, we obtained a relevant interaction with the ME1 (malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was ME1-rs3798890 (p = 2.15 × 10−7). In the regional-wide association study, specifically focused on the FADS1/FASD2/FADS3 and ELOVL (fatty acid elongase) 2/ELOVL 5 regions, we detected several statistically significant associations at p < 0.05. In conclusion, our results confirm a robust role of the FADS cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) reported in a GWAS meta-analysis in other populations (including an SNP in/near each of these LEP, SLC32A1, GCKR, CCNL, COBLL1, and FTO genes); (2) Investigating additional SNPs in/near those genes, also including the RLEP gene; and (3) Undertaking a GWAS to discover new genes. We did not find any statistically significant associations between the previously published SNPs and plasma leptin (Ln) in the whole population adjusting for sex and age. However, on undertaking an extensive screening of other gene variants in those genes to capture a more complete set of SNPs, we found more associations. Outstanding among the findings was the heterogeneity per sex. We detected several statistically significant interaction terms with sex for these SNPs in the candidate genes. The gene most associated with plasma leptin levels was the FTO gene in men (specifically the rs1075440 SNP) and the LEPR in women (specifically the rs12145690 SNP). In the GWAS on the whole population, we found several new associations at the p < 1 × 10−5 level, among them with the rs245908-CHN2 SNP (p = 1.6 × 10−6). We also detected a SNP*sex interaction at the GWAS significance level (p < 5 × 10−8), involving the SLIT3 gene, a gene regulated by estrogens. In conclusion, our study shows that the SNPs selected as relevant for plasma leptin levels in other populations, are not good markers for this Mediterranean population, so supporting those studies claiming a bias when generalizing GWAS results to different populations. These population-specific differences may include not only genetic characteristics, but also age, health status, and the influence of other environmental variables. In addition, we have detected several sex-specific effects. These results suggest that genomic analyses, involving leptin, should be estimated by sex and consider population-specificity for more precise estimations.

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4–7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63–0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64–0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future.

Biomarkers based on DNA methylation are relevant in the field of environmental health for precision health. Although tobacco smoking is one of the factors with a strong and consistent impact on DNA methylation, there are very few studies analyzing its methylation signature in southern European populations and none examining its modulation by the Mediterranean diet at the epigenome-wide level. We examined blood methylation smoking signatures on the EPIC 850 K array in this population (n = 414 high cardiovascular risk subjects). Epigenome-wide methylation studies (EWASs) were performed analyzing differential methylation CpG sites by smoking status (never, former, and current smokers) and the modulation by adherence to a Mediterranean diet score was explored. Gene-set enrichment analysis was performed for biological and functional interpretation. The predictive value of the top differentially methylated CpGs was analyzed using receiver operative curves. We characterized the DNA methylation signature of smoking in this Mediterranean population by identifying 46 differentially methylated CpGs at the EWAS level in the whole population. The strongest association was observed at the cg21566642 (p = 2.2 × 10−32) in the 2q37.1 region. We also detected other CpGs that have been consistently reported in prior research and discovered some novel differentially methylated CpG sites in subgroup analyses. In addition, we found distinct methylation profiles based on the adherence to the Mediterranean diet. Particularly, we obtained a significant interaction between smoking and diet modulating the cg5575921 methylation in the AHRR gene. In conclusion, we have characterized biomarkers of the methylation signature of tobacco smoking in this population, and suggest that the Mediterranean diet can increase methylation of certain hypomethylated sites.