Toenail selenium, plasma selenoprotein P and risk of advanced prostate cancer: A nested case-control study.

Low selenium status may be associated with increased risk of prostate cancer (PC), particularly aggressive PC, and variation in selenoprotein genes may constitute an important modifying factor. We aimed to investigate the association between two selenium status biomarkers [toenail selenium, plasma selenoprotein P (SELENOP)] and risk of advanced, high-grade and advanced-stage PC. We further studied whether variations in selenoprotein genes were associated with PC risk and selenium biomarker concentrations. In the "Diet, Cancer and Health" cohort, 27 178 men aged 50 to 65 years were enrolled from 1993 to 1997. Between baseline and 2012, 1160 cohort participants were diagnosed with advanced PC; among these 462 had high-grade and 281 had advanced-stage disease at diagnosis. Each case was risk set-matched to one control. Toenail selenium and plasma SELENOP concentrations were measured by neutron activation analysis and a SELENOP-ELISA, respectively, and genotyping was performed for 27 selected single nucleotide polymorphisms (SNPs) in 12 selenium pathway genes (including seven selenoproteins) by allele-specific PCR. Toenail selenium and circulating SELENOP concentrations were not associated with advanced, high-grade or advanced-stage PC. After adjustment for multiple testing, none of the genes were associated with PC risk. Neither toenail selenium nor plasma SELENOP was associated with advanced, high-grade or advanced-stage PC.

Genome-wide association study of selenium concentrations.

Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis of toenail Se concentrations, which reflect a longer duration of exposure than blood Se concentrations, including 4162 European descendants from four US cohorts. Toenail Se was measured using neutron activation analysis. We identified a GW-significant locus at 5q14 (P < 1 × 10(-16)), the same locus identified in the published GWAS of blood Se based on independent cohorts. The lead single-nucleotide polymorphism (SNP) explained ∼1% of the variance in toenail Se concentrations. Using GW-summary statistics from both toenail and blood Se, we observed statistical evidence of polygenic overlap (P < 0.001) and meta-analysis of results from studies of either trait (n = 9639) yielded a second GW-significant locus at 21q22.3, harboring CBS (P < 4 × 10(-8)). Proteins encoded by genes at 5q14 and 21q22.3 function in homocysteine (Hcy) metabolism, and index SNPs for each have previously been associated with betaine and Hcy levels in GWAS. Our findings show evidence of a genetic link between Se and Hcy pathways, both involved in cardiometabolic disease.

Scoping the impact of the national child measurement programme feedback on the child obesity pathway: study protocol.

BACKGROUND: The National Child Measurement Programme was established to measure the height and weight of children at primary school in England and provides parents with feedback about their child's weight status. In this study we will evaluate the impact of the National Child Measurement Programme feedback on parental risk perceptions of overweight, lifestyle behaviour and health service use. METHODS: The study will be a prospective cohort study of parents of children enrolled in the National Child Measurement Programme and key service providers from 5 primary care trusts (administrative bodies responsible for providing primary and secondary care services). We will conduct baseline questionnaires, followed by provision of weight feedback and 3 follow up questionnaires over the course of a year. Questionnaires will measure change in parental risk perception of overweight, health behaviours and health service use. Qualitative interviews will be used to identify barriers and facilitators to change. This study will produce preliminary data on National Health Service costs associated with weight feedback and determine which feedback approach (letter and letter plus telephone) is more effective. DISCUSSION: This study will provide the first large scale evaluation of the National Child Measurement Programme feedback. Findings from this evaluation will inform future planning of the National Child Measurement Programme.

Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania.

Selenium deficiency has been implicated in accelerated disease progression and poorer survival among populations infected with HIV in developed countries, yet these associations remain unexamined in developing countries. Among 949 HIV-1-infected Tanzanian women who were pregnant, we prospectively examined the association between plasma selenium levels and survival and CD4 counts over time. Over the 5.7-y median follow-up time, 306 of 949 women died. In a Cox multivariate model, lower plasma selenium levels were significantly associated with an increased risk of mortality (P-value, test for trend = 0.01). Each 0.1 micromol/L increase in plasma selenium levels was related to a 5% (95% CI = 0%-9%) decreased risk of mortality. Plasma selenium levels were not associated with time to progression to CD4 cell count < 200 cells/mm(3) but were weakly and positively related to CD4 cell count in the first years of follow up. Selenium status may be important for clinical outcomes related to HIV disease in sub-Saharan Africa.