Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers

We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.     

TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general population

The cytokines tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55 and p75, and interleukin 6 (IL-6) are involved in host defense against several microbiological agents, in the process of inflammation and also in body weight regulation. In the present study, we sought to assess the influence of age, gender, smoking, and body mass index on plasma levels of TNF-alpha, TNF receptors, and IL-6 in more than 550 adult subjects randomly selected from the Bavarian population. None of the cytokine parameters had a normal distribution and all distributions were significantly skewed. The cytokine plasma levels investigated increased significantly with age, while gender had a relatively weaker influence on the plasma levels. Plasma levels of TNF-alpha, TNF receptors, and IL-6 correlated significantly with the BMI. The study provides insights into factors influencing the cytokine levels investigated in a randomly chosen study sample.     

Calcium Intake and Serum Concentration in Relation to Risk of Cardiovascular Death in NHANES III

Background

Evidence for an association between calcium intake and risk of cardiovascular death remains controversial. By assessing dietary intake, use of supplements, and serum levels of calcium, we aimed to disentangle this link in the third National Health and Nutrition Examination Survey (NHANES III).

Methods

Mortality linkage of NHANES III to death certificate data for those aged 17 years or older (n = 20,024) was used to estimate risk of overall cardiovascular death as well as death from ischemic heart disease (IHD), acute myocardial infarction (AMI), heart failure (HF), and cerebrovascular disease (CD) with multivariate Cox proportional hazards regression analysis.

Results

About 10.0% of the population died of cardiovascular disease and the majority (5.4%) died of IHD. There was increased risk of overall CVD death for those in the bottom 5% of serum calcium compared to those in the mid 90% (HR: 1.51 (95% CI: 1.03–2.22)). For women there was a statistically significant increased risk of IHD death for those with serum calcium levels in the top 5% compared to those in the mid 90% (HR: 1.72 (95%CI: 1.13–2.61)), whereas in men, low serum calcium was related to increased IHD mortality (HR: 2.32 (95% CI 1.14–3.01), P_interaction: 0.306). No clear association with CVD death was observed for dietary or supplemental calcium intake.

Conclusions

Calcium as assessed by serum concentrations is involved in cardiovascular health, though differential effects by sex may exist. No clear evidence was found for an association between dietary or supplementary intake of calcium and cardiovascular death.     

The human peripheral blood mononuclear cell proteome responds to a dietary flaxseed-intervention and proteins identified suggest a protective effect in atherosclerosis

Flaxseed is one of the richest sources of lignans that are converted to enterolactone by the intestinal microflora. Enterolactone has been suggested to be the prime active compound mediating atherosclerosis-protective effects that were shown for flaxseed. The effects of a 1-wk intervention with 0.4 g of flaxseed/kg body weight per day on enterolactone plasma levels in seven healthy men revealed that all participants (PAs) responded with enhanced enterolactone plasma levels. Proteome analysis of peripheral blood mononuclear cells (PBMC) from donors before, during, and after the intervention showed that flaxseed consumption affected significantly the steady-state levels of 16 proteins of which four were altered in a similar manner when blood mononuclear cells were exposed ex vivo to enterolactone. Enhanced levels of peroxiredoxin and reduced levels of the long-chain fatty acid beta-oxidation multienzyme complex may be taken as indicators of a reduced oxidative stress whereas reduced levels of glycoprotein IIIa/II could indicate improved protection from thrombotic and inflammatory processes. In conclusion, the blood mononuclear cell proteome responds to dietary flaxseed intake with changes in a number of atherosclerosis-relevant proteins that may be taken as biomarkers of exposure and some of these changes observed can be attributed to the action of the lignan metabolite enterolactone.     

Validated application of a new high-performance liquid chromatographic method for the determination of selected flavonoids and phenolic acids in human plasma using electrochemical detection

We developed a sensitive method for determination of 23 flavonoids and phenolic acids, which represent phenolic acids and five subclasses of flavonoids. Plasma samples were extracted with selective solid-phase-extraction columns and separated by RP-high-performance liquid chromatography (HPLC). For detection an electrochemical detector was used. Identification and test of purity were carried out via retention times and spectra analyses. Limits of detection varied from 1.45 to 22.27 nmol/l. Recovery varied from 81% to 106%. Reproducibility for all analytes was below 10% (coefficient of variation, CV (%)) and ranged between 3.1% and 9.8%. This method can be applied to samples from interventional studies as well as observational studies.     

IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3)

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.     

Associations between thyroid hormones and serum metabolite profiles in an euthyroid population

Metabolomics - The aim was to characterise associations between circulating thyroid hormones—free thyroxine (FT4) and thyrotropin (TSH)—and the metabolite profiles in serum samples from...     

Differences in the physical properties of lipid monolayers and bilayers on a spherical solid support.

A monolayer of 1,2-dipalmitoyl-d62-glycero-3-phosphocholine (DPPC-d62) coated onto silanized silica beads (spherical supported monolayer: SSM) is studied by 2H-NMR and DSC. The results are compared with those obtained from a single bilayer on the same solid support (spherical supported vesicles: SSV) and from multilamellar vesicles (MLV). The phase transition temperature (Tm) of the SSMs is significantly higher than that of the bilayer systems and the extent of this difference depends on the lipid density in the monolayer that is determined during its preparation. 2H-NMR reveals a gel and fluid phase coexistence in the SSM transition region. A comparison of the 2H-NMR line shapes suggests the presence of highly curved structures for the fluid phase of the SSM samples. From a comparison of SSM and SSV transverse relaxation in the fluid phase we can conclude that the lateral diffusion coefficient D1 in supported monolayers is similar to that in bilayers.