Relative validity of a semiquantitative food frequency questionnaire designed for schoolchildren in western Greece

<p>Abstract</p> <p>Background</p> <p>The use of food frequency questionnaires (FFQs) has become increasingly important in epidemiologic studies. During the past few decades, a wide variety of nutritional studies have used the semiquantitative FFQ as a tool for assessing and evaluating dietary intake. One of the main concerns in a dietary analysis is the validity of the collected dietary data.</p> <p>Methods</p> <p>This paper discusses several methodological and statistical issues related to the validation of a semiquantitative FFQ. This questionnaire was used to assess the nutritional habits of schoolchildren in western Greece. For validation purposes, we selected 200 schoolchildren and contacted their respective parents. We evaluated the relative validity of 400 FFQs (200 children's FFQs and 200 parents' FFQs).</p> <p>Results</p> <p>The correlations between the children's and the parents' questionnaire responses showed that the questionnaire we designed was appropriate for fulfilling the purposes of our study and in ranking subjects according to food group intake.</p> <p>Conclusion</p> <p>Our study shows that the semiquantitative FFQ provides a reasonably reliable measure of dietary intake and corroborates the relative validity of our questionnaire.</p

Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments

Influence of metastatic disease on the usefulness of uracil pharmacokinetics as a screening tool for DPD activity in colorectal cancer patients

Experimentele farmacotherapi

Group level validation of protein intakes estimated by 24-hour diet recall and dietary questionnaires against 24-hour urinary nitrogen in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

A calibration approach was developed to correct for systematic between-cohort dietary measurement errors in the European Prospective Investigation into Cancer and Nutrition (EPIC), a large multicenter cohort study. To validate the 24-h diet recalls (24-HDRs) as reference measurements for between-cohort calibration, we estimated the agreement between center mean nitrogen (N) and total energy intakes and mean 24-h urinary N. Similar analyses using N and energy intake data from different dietary questionnaires (DQs) used at study baseline were conducted to estimate the effect of the calibration approach. This study was conducted between 1995 and 1999, and involved 1103 volunteers of both genders from 12 centers participating in European Prospective Investigation into Cancer and Nutrition. Pearson's correlation coefficients were weighted for study center sample size. When both genders were considered together (n = 22), the correlation coefficients between the center mean log-transformed urinary estimates and the center mean log-transformed dietary N estimates from the 24-HDRs were 0.86 and 0.94 after exclusion of outliers. The corresponding correlation with the DQs was 0.53. When center mean total energy intakes were regressed on center mean urinary N, the correlation remained slightly higher with 24-HDRs (0.91; 0.95 after exclusion of outliers) than DQs (0.86). When stratified by gender, these correlations were systematically higher in men than women with both dietary methods. The beta regression coefficients were not significantly different from 1 when mean N (or total energy intakes) from 24-HDR or DQ were regressed on urinary estimates, except with N from 24-HDRs in men and, in most cases, after adjustment for age, body mass index, and sex with both genders together. This suggests that overall the systematic bias across centers is of uniform magnitude. Although relatively high correlations were observed between urinary N and both dietary methods in men, the errors in DQs tend to vary in both directions (under- and over-reporting) in contrast with 24-HDRs in women. This observation may have implications on the dietary measurement error characteristics and support the potential benefit of between-cohort calibration

Evaluation of predictive tests for screening for dihydropyrimidine dehydrogenase deficiency

5-Fluorouracil (5-FU) is rapidly degraded by dihyropyrimidine dehydrogenase (DPD). Therefore, DPD deficiency can lead to severe toxicity or even death following treatment with 5-FU or capecitabine. Different tests based on assessing DPD enzyme activity, genetic variants in DPYD and mRNA variants have been studied for screening for DPD deficiency, but none of these are implemented broadly into clinical practice. We give an overview of the tests that can be used to detect DPD deficiency and discuss the advantages and disadvantages of these test

Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients

Background: Dihydropyrimidine dehydrogenase (DPD) catabolizes approximately 85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. Methods: The TOSCA Italian randomized trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, ten 49 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, rs75017182 C>G), were retrospectively tested for associations with > grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False Discovery Rate (FDR) procedure was used. 55 Results: FAEs occurred in 194/508 assessable patients (38.2%). In the association analysis, FAEs 56 occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT 57 analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), 58 *2A rs3918290 A allele carriers (FDR <0.0001), rs2297595 GG genotype carriers (FDR=0.0014). 59 Neutropenia was the commonest FAEs (28.5%). *6 rs1801160 (FDR <.0001), and *2A 60 rs3918290 (FDR =0.0004) variant alleles were significantly associated with time to neutropenia. 61 Conclusions: This study adds evidence on the role of DPYD pharmacogenetics for safety of 62 patients undergoing fluoropyrimidine-based chemotherapy

European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics

The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres