Experimental evidence indicates that exercise performed at different times of the day may affect circadian rhythms and circadian disruption has been linked to breast and prostate cancer. We examined ...in a population‐based case‐control study (MCC‐Spain) if the time‐of‐day when physical activity is done affects prostate and breast cancer risk. Lifetime recreational and household physical activity was assessed by in‐person interviews. Information on time‐of‐day of activity (assessed approximately 3 years after the assessment of lifetime physical activity and confounders) was available for 781 breast cancer cases, 865 population female controls, 504 prostate cases and 645 population male controls from 10 Spanish regions, 2008‐2013. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for different activity timings compared to inactive subjects using unconditional logistic regression adjusting for confounders. Early morning (8‐10 am) activity was associated with a protective effect compared to no physical activity for both breast (OR = 0.74, 95% CI = 0.48‐1.15) and prostate cancer (OR = 0.73, 95% CI = 0.44‐1.20); meta‐OR for the two cancers combined 0.74 (95%CI = 0.53‐1.02). There was no effect observed for breast or prostate cancer for late morning to afternoon activity while a protective effect was also observed for evening activity only for prostate cancer (OR = 0.75, 95% CI = 0.45‐1.24). Protective effects of early morning activity were more pronounced for intermediate/evening chronotypes for both cancers. This is the first population‐based investigation identifying a differential effect of timing of physical activity on cancer risk with more pronounced effects for morning hour activity. Our results, if confirmed, may improve current physical activity recommendations for cancer prevention.
What's new?
Exercise protects against a variety of cancers, but does time of day matter? Disrupting the body's circadian rhythm can boost cancer risk. Here, the authors compared breast and prostate cancer risk among people who exercised in the early morning, late morning, afternoon, and evening. They conducted a population‐based case‐control study, in which participants filled out a questionnaire about their patterns of sleeping, eating, and exercising. Exercising in the early morning appeared to be more strongly protective against breast and prostate cancer than exercising later in the day. Evening exercise appeared to have a moderate protective effect on prostate cancer.
This study sought to compare the efficacy of drug-eluting balloons (DEB) with that of everolimus-eluting stents (EES) in patients with bare-metal stents (BMS) in-stent restenosis (ISR).
Treatment of ...patients with ISR remains a challenge.
This was a prospective, multicenter, randomized trial comparing DEB with EES in patients with bare-metal stents (BMS) in-stent restenosis (ISR). The primary endpoint was the minimal lumen diameter at 9 months' follow-up.
A total of 189 patients with BMS-ISR from 25 Spanish sites were included (95 were allocated to DEB and 94 to EES). Procedural success was achieved in all patients. At late angiography (median 249 days; 92% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm, p < 0.001; absolute mean difference: 0.35 mm; 95% confidence interval CI: 0.16 to 0.53) and a lower percent of diameter stenosis (13 ± 17% vs. 25 ± 20%, p < 0.001). However, late loss (0.04 ± 0.5 mm vs. 0.14 ± 0.5 mm, p = 0.14) and binary restenosis rate (4.7% vs. 9.5%, p = 0.22) were very low and similar in both groups. Clinical follow-up (median 365 days) was obtained in all (100%) patients. Occurrences of the combined clinical outcome measure (cardiac death, myocardial infarction, and target vessel revascularization; 6% vs. 8%; hazard ratio HR: 0.76; 95% CI: 0.26 to 2.18, p = 0.6) and the need for target vessel revascularization (2% vs. 6%; HR: 0.32: 95% CI: 0.07 to 1.59, p = 0.17) were similar in the 2 groups.
In patients with BMS-ISR, both DEB and EES provided excellent clinical results with a very low rate of clinical and angiographic recurrences. However, compared with DEB, EES provide superior late angiographic findings. (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs. Everolimus-eluting Stent RIBS V; NCT01239953).
Somatic mutational mosaicism is a common feature of monogenic genetic disorders, particularly in diseases such as retinoblastoma, with high rates of de novo mutations. The detection and ...quantification of mosaicism is particularly relevant in these diseases, since it has important implications for genetic counseling, patient management, and probably also on disease onset and progression. In order to assess the rate of somatic mosaicism (high- and low-level mosaicism) in sporadic retinoblastoma patients, we analyzed a cohort of 153 patients with sporadic retinoblastoma using ultra deep next-generation sequencing. High-level mosaicism was detected in 14 out of 100 (14%) bilateral patients and in 11 out of 29 (38%) unilateral patients in whom conventional Sanger sequencing identified a pathogenic mutation in blood DNA. In addition, low-level mosaicism was detected in 3 out of 16 (19%) unilateral patients in whom conventional screening was negative in blood DNA. Our results also reveal that mosaicism was associated to delayed retinoblastoma onset particularly in unilateral patients. Finally we compared the level of mosaicism in different tissues to identify the best DNA source to identify mosaicism in retinoblastoma patients. In light of these results we recommended analyzing the mosaic status in all retinoblastoma patients using accurate techniques such as next-generation sequencing, even in those cases in which conventional Sanger sequencing identified a pathogenic mutation in blood DNA. Our results suggest that a significant proportion of those cases are truly mosaics that could have been overlooked. This information should be taking into consideration in the management and genetic counseling of retinoblastoma patients and families.
Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in ...patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer.
•Association between colorectal cancer and proximity to industries was investigated.•Colorectal cancer was detected near industries overall for all distances.•Excess risk was higher near industries ...releasing pollution to air than water.•Industry of metal, glass, chemical, food and organic solvents showed excess risks.•Risk found near plants releasing nonylphenol, antimony, naphthalene, and manganese.
Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary.
To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain).
MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects’ residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders.
Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44–2.87) to 3 km (1.26; 1.00–1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77–4.00), surface treatment of metals (1.48; 1.08–2.02), glass and mineral fibers (2.06; 1.39–3.07), organic chemical industry (4.80; 3.20–7.20), inorganic chemical industry (6.74; 4.38–10.36), food/beverage sector (3.34; 2.38–4.68), and surface treatment using organic solvents (6.16; 4.06–9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91–14.28), antimony (5.30; 3.45–8.15), naphthalene (3.11; 2.16–4.49), organotin compounds (2.64; 1.76–3.98), manganese (2.53; 1.63–3.93), dichloromethane (2.52; 1.74–3.66), and vanadium (2.49; 1.59–3.91).
Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer.
Objectives This study sought to compare the efficacy of drug-eluting balloons (DEB) with that of everolimus-eluting stents (EES) in patients with bare-metal stents (BMS) in-stent restenosis (ISR). ...Background Treatment of patients with ISR remains a challenge. Methods This was a prospective, multicenter, randomized trial comparing DEB with EES in patients with bare-metal stents (BMS) in-stent restenosis (ISR). The primary endpoint was the minimal lumen diameter at 9 months' follow-up. Results A total of 189 patients with BMS-ISR from 25 Spanish sites were included (95 were allocated to DEB and 94 to EES). Procedural success was achieved in all patients. At late angiography (median 249 days; 92% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm, p < 0.001; absolute mean difference: 0.35 mm; 95% confidence interval CI: 0.16 to 0.53) and a lower percent of diameter stenosis (13 ± 17% vs. 25 ± 20%, p < 0.001). However, late loss (0.04 ± 0.5 mm vs. 0.14 ± 0.5 mm, p = 0.14) and binary restenosis rate (4.7% vs. 9.5%, p = 0.22) were very low and similar in both groups. Clinical follow-up (median 365 days) was obtained in all (100%) patients. Occurrences of the combined clinical outcome measure (cardiac death, myocardial infarction, and target vessel revascularization; 6% vs. 8%; hazard ratio HR: 0.76; 95% CI: 0.26 to 2.18, p = 0.6) and the need for target vessel revascularization (2% vs. 6%; HR: 0.32: 95% CI: 0.07 to 1.59, p = 0.17) were similar in the 2 groups. Conclusions In patients with BMS-ISR, both DEB and EES provided excellent clinical results with a very low rate of clinical and angiographic recurrences. However, compared with DEB, EES provide superior late angiographic findings. (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs. Everolimus-eluting Stent RIBS V; NCT01239953 )
Abstract
Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have ...shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with ...advanced lung disease.
Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations.
Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV
% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia.
ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.
The most representative indicator of vitamin D status in clinical practice is 25(OH)D
, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study ...is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39-50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE-LC-MS/MS platform. The association between participant's characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D
concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)
D
/25(OH)D
) and a higher R4 (24,25(OH)
D
/1,25(OH)
D
) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D
/Vit D
) and R3 (24,25(OH)
D
/25(OH)D
), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.
The actual usefulness of cardiovascular (CV) risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Prospective multicentre ...study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk.
A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples, and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of cancer therapy. At baseline, 893 patients (67.4%) presented at least one risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity (CTox) and all-cause mortality hazard ratio (HR) 1.79 (95% confidence interval, CI 1.16-2.76) for SCORE 5-9 and HR 4.90 (95% CI 2.44-9.82) for SCORE ≥10 when compared with patients with lower SCORE (0-4).
This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline CV risk assessment using SCORE predicted severe CTox and all-cause mortality. Therefore, its use should be considered in the evaluation of cancer patients.
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