Genetic Variability of the mTOR Pathway and Prostate Cancer Risk in the European Prospective Investigation on Cancer (EPIC)

The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78–0.94, p = 1.3×10−3 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.6×10−4 for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer

Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC).

BACKGROUND: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. OBJECTIVE: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. DESIGN: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m²) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. RESULTS: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. CONCLUSION: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.This article was originally published in American Journal of Clinical Nutrition March 2015 (published January 14, 2015), doi: 10.3945/​ajcn.114.100065

Comparison of Motor Difficulties Measured in the First Year of School among Children Who Attended Rural Outdoor or Urban Conventional Kindergartens

Background: Kindergartens can potentially contribute substantially to the daily level of physical activity and development of motor skills and might be an ideal setting for improving these as a public health initiative. We aimed to examine whether children from rural outdoor kindergartens had a lower risk of motor difficulties than children from urban conventional kindergartens. Methods: Motor test results were measured during the first school year by school health nurses using a six-item test of gross- and fine motor skills (jumping, handle a writing tool, cutting with a scissor following a line, one-leg stand on each leg, throwing and grabbing). Register-based information was available on potential confounding factors. Results: We included 901 children from outdoor kindergartens and 993 from conventional kindergartens with a mean (SD) age of 6.5 years (0.4). The children from the two types of kindergarten differed according to demographic information, with outdoor kindergarten children more often being from more affluent families (long maternal education level: 47.5% vs. 31.0%, p &lt; 0.0001) and fewer girls attending the outdoor kindergartens (42.7% vs. 49.5%, p = 0.003). In the adjusted models, we found no evidence of differences in the risk of motor difficulties between children attending either type of kindergarten (OR: 0.95, 95%CI: 0.71; 1.27, p = 0.72). Conclusion: Our results do not support outdoor kindergartens as a potential intervention to improve motor abilities among children. Randomized controlled trials are needed to confirm these findings

Exploring targeted preventive health check interventions – a realist synthesis

Abstract Background Preventive health checks are assumed to reduce the risk of the development of cardio-metabolic disease in the long term. Although no solid evidence of effect is shown on health checks targeting the general population, studies suggest positive effects if health checks target people or groups identified at risk of disease. The aim of this study is to explore why and how targeted preventive health checks work, for whom they work, and under which circumstances they can be expected to work. Methods The study is designed as a realist synthesis that consists of four phases, each including collection and analysis of empirical data: 1) Literature search of systematic reviews and meta-analysis, 2) Interviews with key-stakeholders, 3) Literature search of qualitative studies and grey literature, and 4) Workshops with key stakeholders and end-users. Through the iterative analysis we identified the interrelationship between contexts, mechanisms, and outcomes to develop a program theory encompassing hypotheses about targeted preventive health checks. Results Based on an iterative analysis of the data material, we developed a final program theory consisting of seven themes; Target group; Recruitment and participation; The encounter between professional and participants; Follow-up activities; Implementation and operation; Shared understanding of the intervention; and Unintended side effects. Overall, the data material showed that targeted preventive health checks need to be accessible, recognizable, and relevant for the participants’ everyday lives as well as meaningful to the professionals involved. The results showed that identifying a target group, that both benefit from attending and have the resources to participate pose a challenge for targeted preventive health check interventions. This challenge illustrates the importance of designing the recruitment and intervention activities according to the target groups particular life situation. Conclusion The results indicate that a one-size-fits-all model of targeted preventive health checks should be abandoned, and that intervention activities and implementation depend on for whom and under which circumstances the intervention is initiated. Based on the results we suggest that future initiatives conduct thorough needs assessment as the basis for decisions about where and how the preventive health checks are implemented

Additional file 1 of Exploring targeted preventive health check interventions – a realist synthesis

Additional file 1