Dietary assessment in Whitehall II: comparison of 7d diet diary and food-frequency questionnaire and validity against biomarkers

The aim of the present cross-sectional study was to examine the agreement and disagreement between a 7 d diet diary (7DD) and a self-administered machine-readable food-frequency questionnaire (FFQ) asking about diet in the previous year, and to validate both methods with biomarkers of nutrient intake. The subjects were an age- and employment-grade-stratified random subsample of London-based civil servants (457 men and 403 women), aged 39–61 years, who completed both a 7DD and a FFQ at phase 3 follow-up (1991–1993) of the Whitehall II study. Mean daily intakes of dietary energy, total fat, saturated, monounsaturated and polyunsaturated fatty acids, linoleic acid, total carbohydrate excluding fibre, sugars, starch, dietary fibre, protein, vitamin C, vitamin E (as α-tocopherol equivalents), folate, carotenes (as total β-carotene activity), Fe, Ca, Mg, K and alcohol were measured. Serum cholesteryl ester fatty acids (CEFA), plasma α-tocopherol and β-carotene were also measured as biomarkers. Estimates of mean energy intake from the two methods were similar in men, and some 10 % higher according to the FFQ in women. Compared with the 7DD, the FFQ tended to overestimate plant-derived micronutrient intakes (carotenes from FFQ v. 7DD men 2713 (SD 1455) V. 2180 (sd 1188) μg/d, women 3100 (sd 1656) v. 2221 (sd 1180) μg/d, both differences P<0·0001) and to underestimate fat intake. Against plasma β-carotene/cholesterol, carotene intake was as well estimated by the FFQ as the 7DD (Spearman rank correlations, men 0·32 v. 0·30, women 0·27 v. 0·22, all P≤0·0001, energy-adjusted data). Ranking of participants by other nutrient intakes tended to be of the same order according to the two dietary methods, e.g. rank correlations for CEFA linoleic acid against FFQ and 7DD estimates respectively, men 0·38 v. 0·41, women 0·53 v. 0·62, all P≤0·0001, energy-adjusted % fat). For α-tocopherol there were no correlations between plasma level and estimated intakes by either dietary method. Quartile agreement for energy-adjusted nutrient intakes between the two self-report methods was in the range 37–50 % for men and 32–44 % for women, and for alcohol, 57 % in both sexes. Disagreement (misclassification into extreme quartiles of intake) was in the range 0–6 % for both sexes. The dietary methods yielded similar prevalences (about 34 %) of low energy reporters. The two methods show satisfactory agreement, together with an expected level of systematic differences, in their estimates of nutrient intake. Against the available biomarkers, the machine-readable FFQ performed well in comparison with the manually coded 7DD in this study population. For both methods, regression-based adjustment of nutrient intake to mean dietary energy intake by gender appears on balance to be the optimal approach to data presentation and analysis, in view of the complex problem of low energy reporting

New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid

Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F2 (8-iso-PGF2), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF2 and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF2 increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2274–9

Antibody response to pneumococcal and influenza vaccination in patients with rheumatoid arthritis receiving abatacept

Background Patients with rheumatoid arthritis (RA), including those treated with biologics, are at increased risk of some vaccine-preventable infections. We evaluated the antibody response to standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 2011–2012 trivalent seasonal influenza vaccine in adults with RA receiving subcutaneous (SC) abatacept and background disease-modifying anti-rheumatic drugs (DMARDs). Methods Two multicenter, open-label sub-studies enrolled patients from the ACQUIRE (pneumococcal and influenza) and ATTUNE (pneumococcal) studies at any point during their SC abatacept treatment cycle following completion of ≥3 months’ SC abatacept. All patients received fixed-dose abatacept 125 mg/week with background DMARDs. A pre-vaccination blood sample was taken, and after 28 ± 3 days a final post- vaccination sample was collected. The primary endpoint was the proportion of patients achieving an immunologic response to the vaccine at Day 28 among patients without a protective antibody level to the vaccine antigens at baseline (pneumococcal: defined as ≥2-fold increase in post-vaccination titers to ≥3 of 5 antigens and protective antibody level of ≥1.6 μg/mL to ≥3 of 5 antigens; influenza: defined as ≥4-fold increase in post-vaccination titers to ≥2 of 3 antigens and protective antibody level of ≥1:40 to ≥2 of 3 antigens). Safety and tolerability were evaluated throughout the sub-studies. Results Pre- and post-vaccination titers were available for 113/125 and 186/191 enrolled patients receiving the PPSV23 and influenza vaccine, respectively. Among vaccinated patients, 47/113 pneumococcal and 121/186 influenza patients were without protective antibody levels at baseline. Among patients with available data, 73.9 % (34/46) and 61.3 % (73/119) met the primary endpoint and achieved an immunologic response to PPSV23 or influenza vaccine, respectively. In patients with pre- and post-vaccination data available, 83.9 % in the pneumococcal study demonstrated protective antibody levels with PPSV23 (titer ≥1.6 μg/mL to ≥3 of 5 antigens), and 81.2 % in the influenza study achieved protective antibody levels (titer ≥1:40 to ≥2 of 3 antigens) at Day 28 post-vaccination. Vaccines were well tolerated with SC abatacept with background DMARDs. Conclusions In these sub-studies, patients with RA receiving SC abatacept and background DMARDs were able to mount an appropriate immune response to pneumococcal and influenza vaccines. Trial registration NCT00559585 (registered 15 November 2007) and NCT00663702 (registered 18 April 2008)

Studies of jet quenching within a partonic transport model

Background: Finite mixture models posit the existence of a latent categorical variable and can be used for probabilistic classification. The authors illustrate the use of mixture models for dietary pattern analysis. An advantage of this approach is taking classification uncertainty into account. Methods: Participants were a random sample of women from the European Prospective Investigation into Cancer. Food consumption was measured using dietary questionnaires. Mixture models identified latent classes in food consumption data, which were interpreted as dietary patterns. Results: Among various assumptions examined, models allowing the variance of foods to vary within and between classes fit better than alternatives assuming constant variance (the K-means method of cluster analysis also makes the latter assumption). An eight-class model was best fitting and five patterns validated well in a second random sample. Patterns with lower classification uncertainty tended to be better validated. One pattern showed low consumption of foods despite being associated with moderate body mass index. Conclusion: Mixture modelling for dietary pattern analysis has advantages over both factor and cluster analysis. In contrast to these other methods, it is easy to estimate pattern prevalence, to describe patterns and to use patterns to predict disease taking classification uncertainty into account. Owing to substantial error in food consumptions, any analysis will usually find some patterns that cannot be well validated. While knowledge of classification uncertainty may aid pattern evaluation, any method will better identify patterns from food consumptions measured with less error. Mixture models may be useful to identify individuals who under-report food consumption

The ISB Cancer Genomics Cloud: A Flexible Cloud-Based Platform for Cancer Genomics Research.

The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute to explore new approaches to computing on large cancer datasets in a cloud environment. With a focus on Data as a Service, the ISB-CGC offers multiple avenues for accessing and analyzing The Cancer Genome Atlas, TARGET, and other important references such as GENCODE and COSMIC using the Google Cloud Platform. The open approach allows researchers to choose approaches best suited to the task at hand: from analyzing terabytes of data using complex workflows to developing new analysis methods in common languages such as Python, R, and SQL; to using an interactive web application to create synthetic patient cohorts and to explore the wealth of available genomic data. Links to resources and documentation can be found at www.isb-cgc.or

Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer

The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from colorectal cancer patients [SEARCH (n=case 192, controls 96)], breast cancer patients [ABC (n=case 364, controls 96)] and the European Prospective Investigation of Cancer [EPIC-Norfolk (n=breast 228, colorectal 225, controls 895)] were analysed. The EPIC samples were collected 2–5 years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population, the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus, IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI

Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.Published versio