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Biomedical subjects

John C Mathers

Publications and source records attributed to John C Mathers.

At least 19 recordsLinked to original sources
PubMed2007

The biological revolution: understanding the impact of SNPs on diet-cancer interrelationships.

Evidence is accumulating that individual risk of neoplasia depends on complex interactions among genetic inheritance, a range of exposures both in utero and in postnatal life, and the play of chance. Knowledge of the portfolio of genetic variants that confer susceptibility or resistance to cancer is limited, and there is potential for genome-wide scans and hypothesis-driven studies to reveal novel polymorphisms and haplotypes that modify risk. There is only fragmentary evidence of the scale and nature of diet-gene interactions that modulate risk of neoplasia, but it seems probable that such interactions will play a significant role as they do in other complex diseases including cardiovascular disease and type 2 diabetes. All existing evidence about diet-gene interactions and cancer risk comes from observational studies, and it will be necessary to undertake intervention studies to test the hypotheses generated by epidemiologic investigations. Because it is very unlikely that primary cancer will be an endpoint in dietary intervention studies in the foreseeable future, development of robust surrogate endpoints is a high priority. Emerging biological science using epigenomics, proteomics, and other molecular technologies appears to offer novel approaches to the discovery and validation of surrogate endpoints.

Diet↗
PubMed2006

Healthy eating: perceptions and practice (the ASH30 study).

Perceptions of healthy eating may influence food intake. Anthropometric and dietary data were collected from 197 respondents (average age 32.5 years: 2000/2001) in Northumberland (78%) and elsewhere in the UK (22%). A questionnaire and two 3-day food diaries were completed. Foods consumed were assigned to one of five food categories from The Balance of Good Health. This paper explores respondents' concepts of 'healthy eating' and responses to the statement, 'My eating patterns are healthy' and compares responses with measured intakes for each of the five food categories. Fifty-three respondents disagreed, 62 neither agreed nor disagreed and 82 agreed with the statement. Intakes of foods containing fat and/or sugar, fruit and vegetables and meat, fish and alternatives were significantly different between the three response groups. The 'agree' group had the highest intake of fruit and vegetables and the lowest intake of foods containing fat and/or sugar and meat, fish and alternatives. A significantly higher proportion of individuals from the highest socio-economic group agreed with the statement. Significantly more individuals with Body Mass Indexes in the two lower quartiles agreed with the statement. This paper shows a relationship between perceptions of eating patterns and socio-economic status, adiposity and measured food intake.

Adult↗
PubMed2006

Proteomic analysis reveals field-wide changes in protein expression in the morphologically normal mucosa of patients with colorectal neoplasia.

Models for the pathogenesis of colorectal cancer tend to focus on the localized lesion, with less attention paid to changes in normal-appearing mucosa. Here we used two-dimensional gel electrophoresis and mass spectrometry to define patterns of protein expression in morphologically normal colonic mucosa from 13 healthy subjects, 9 patients with adenomatous polyps, and 9 with cancer. Tumor samples were also compared with the normal mucosa. Systematic gel comparisons identified a total of 839 spots that differed significantly between one or more groups (P < 0.05). Principle component analysis indicated that the first three components accounted for approximately 37% of the total variation and provided clear evidence that flat mucosa from healthy subjects differed significantly from that of patients with polyps or cancer. Sixty-one proteins differed significantly between mucosa from healthy subjects and all other tissue types, and 206 differed significantly between healthy mucosa and polyp mucosa. Several of the proteins showing significant underexpression in tumor tissue were cytokeratins and other cytoskeletal components. In contrast, cytokeratins, including several isoforms of cytokeratin 8, were overexpressed in apparently normal mucosa from polyp and cancer patients compared with mucosa from healthy subjects. These findings indicate that protein expression in the apparently normal colonic mucosal field is modified in individuals with neoplastic lesions at sites distant from the lesion. Recognition and further characterization of this field effect at the molecular level may provide protein biomarkers of susceptibility to colorectal cancer and facilitate development of hypotheses for the role of diet and other environmental factors in its causation.

Aged↗
PubMed2006

Nutritional modulation of ageing: genomic and epigenetic approaches.

Dietary factors have a profound effect on many aspects of health including ageing and do so, at least partly, through interactions with the genome which result in altered gene expression. The application of high throughput genomics technologies in nutritional research (nutrigenomics) offers a new approach to understanding the molecular mechanisms by which nutrition affects ageing. To date, transcriptional profiling techniques have been applied in studies of the mode of action of energy (caloric) restriction. Two further areas which appear to be particularly promising are (i) nutritional modulation of DNA damage and repair and (ii) nutritional modulation of epigenetic markings. Epigenetic-mediated changes in gene expression in response to dietary and other lifestyle exposures appear to be a major molecular mechanism linking environmental factors with the genome with consequences for cell function and health throughout the life course.

Aged↗
PubMed2006

Longitudinal change in food habits between adolescence (11-12 years) and adulthood (32-33 years): the ASH30 Study.

BACKGROUND: Links between diet in childhood and the prevention of disease in adulthood have been established. This longitudinal dietary survey provided quantitative evidence of dietary change from adolescence to adulthood, in Northumberland, England. OBJECTIVE: To report longitudinal dietary change in 198 respondents between the ages of 12 and 33 years, to explore dietary 'tracking' between the same time points and to describe the effects of gender, socio-economic status and location on dietary change. METHODS: A longitudinal study recorded dietary change from adolescence to adulthood. Two 3-day food diaries were collected in 1980 and 2000 from the same 198 respondents. Foods consumed were assigned to the five categories in the Balance of Good Health (BGH). Demographic and socio-economic information were obtained in 1980 and 2000. RESULTS: Intakes of foods containing fat and/ or sugar and milk and dairy foods decreased (p < 0.01 and p < 0.031, respectively), while intakes of fruits and vegetables increased (p < 0.01). Intakes of bread, other cereals and potatoes (p = 0.002, r = +0.219); fruits and vegetables (p < 0.01, r = +0.256) and meat, fish and alternatives (p = 0.026, r = +0.158) 'tracked' from adolescence to adulthood. Men had increased intake from meat, fish and alternatives and decreased milk and dairy foods more than female respondents (p = 0.003 and p = 0.019). Respondents who had moved away from Northumberland had a greater increase in intake of fruits and vegetables compared with those who remained in the local (p = 0.010). Individuals who had moved to a lower socio-economic group had increased their intake of bread, other cereals and potatoes (p = 0.040). CONCLUSION: Food intake changed considerably in a direction more in the line with current dietary recommendations. Food intake in adolescence was a significant, but not strong, predictor of intake in adulthood. Dietary change is influenced by variables including gender, location and socio-economic status.

Adult↗
PubMed2006

Bioethics in human nutrigenomics research: European Nutrigenomics Organisation workshop report.

As part of its work on setting standards and establishing guidelines for nutrigenomics research, the European Nutrigenomics Organisation (NuGO) is developing bioethical guidelines for those engaged in human nutrigenomics studies. A NuGO working group developed a set of draft guidelines addressing four areas: (1) information and consenting prior to a nutrigenomics study; (2) the generation and use of genotype information; (3) the establishment and maintenance of biobanks; (4) the exchange of samples and data. NuGO convened a workshop with a panel of invited external experts to assess the draft guidelines. The panel of experts confirmed that these areas are important and that the development of specific bioethical guidelines for nutrigenomics research would therefore enhance the application of established international guidelines in this field of biomedical research.

Biomedical Research↗
PubMed2006

Accuracy of estimates of food portion size using food photographs--the importance of using age-appropriate tools.

BACKGROUND: In order to obtain a measure of nutrient intake, a measure or estimate of the amount of food consumed is required. Weighing foods imposes a large burden on subjects, often resulting in underreporting. Tools are available to assist subjects in providing an estimate of portion size and these include food photographs. The application of these tools in improving portion size estimation by children has not been investigated systematically. OBJECTIVES: To assess the accuracy with which children are able to estimate food portion sizes using food photographs designed for use with adults, and to determine whether the accuracy of estimates is improved when age-appropriate portion size photographs are provided. DESIGN: Original data from three separate studies, on the accuracy of portion size estimates by adults using food photographs, by children using adult photographs and by children using age-appropriate photographs, are analysed and compared. SUBJECTS: One hundred and thirty-five adults aged 18 to 90 years and 210 children aged 4 to 11 years. RESULTS: Children's estimates of portion sizes using age-appropriate food photographs were significantly more accurate (an underestimate of 1% on average) than estimates using photographs designed for use with adults (an overestimate of 45% on average). Accuracy of children's estimates of portion size using age-appropriate photographs was not significantly different from that of adults. Children overestimated a food's weight by 18% on average and adults underestimated by 5%. CONCLUSIONS: Providing children with food photographs depicting age-appropriate portion sizes greatly increases the accuracy of portion size estimates compared with estimates using photographs designed for use with adults.

Adolescent↗
PubMed2006

Plant foods for human health: research challenges.

Plants provide the major part of human food intake. Whilst advances in agronomic characteristics (improved yield and better pest and disease resistance) continue to be a very high priority, there is increasing opportunity to enhance the nutritional value of plant based diets by improving the nutritional quality of staple foods. We now have proof of principle that genetic engineering can be used to produce plant-derived human vaccines. In relation to plant foods for human health, the research challenges include understanding: (1) why certain foods cause adverse reactions in some individuals but not in others; (2) the mechanisms of action of apparently 'protective' foods such as fruits and vegetables. There is also a need to develop much more informative and robust methods for measuring dietary exposure to specific plant foods or food constituents, including both recent exposure, for which a metabolomics approach may be particularly helpful, and long-term exposure.

Consumer Product Safety↗
PubMed2005

Randomised controlled trial evaluating lifestyle interventions in people with impaired glucose tolerance.

AIM: To evaluate the effectiveness of lifestyle interventions in people with impaired glucose tolerance (IGT). METHODS: Participants with IGT (n=78), diagnosed on two consecutive oral glucose tolerance tests (OGTTs), were randomly assigned to a 2-year lifestyle intervention or to a control group. Main outcome measures were changes from baseline in: nutrient intake; physical activity; anthropometry, glucose tolerance and insulin sensitivity. Measurements were repeated at 6, 12 and 24 months follow-up. RESULTS: After 24 months follow-up, there was a significant fall in total fat consumption (difference in change between groups (Delta intervention-Delta control)= -17.9, 95% confidence interval (CI) -33.6 to -2.1g/day) as a result of the intervention. Body mass was significantly lower in the intervention group compared with controls after 6 months (-1.6, 95% CI -2.9 to -0.4 kg) and 24 months (-3.3, 95% CI -5.7 to -0.89 kg). Whole body insulin sensitivity, assessed by the short insulin tolerance test (ITT), improved after 12 months in the intervention group (0.52, 95% CI 0.15-0.89%/min). CONCLUSIONS: These findings complement the findings of the Finnish Diabetes Prevention Study and the American Diabetes Prevention Study, both of which tested intensive interventions, by showing that pragmatic lifestyle interventions result in improvements in obesity and whole body insulin sensitivity in individuals with IGT, without change in other cardiovascular risk factors.

Adult↗
PubMed2005

Postprandial glycaemic, lipaemic and haemostatic responses to ingestion of rapidly and slowly digested starches in healthy young women.

The objective of the present study was to investigate the postprandial metabolism of two starches with contrasting rates of hydrolysis in vitro. Characterized using the Englyst method of in vitro starch classification, C*Set 06 598 contained predominantly rapidly digestible starch and C*Gel 04 201 contained predominantly slowly digestible starch. Each test starch, naturally enriched with 13C, was fed to ten healthy female volunteers as part of a moderate fat test meal (containing 75 g test starch and 21 g fat), in a double-blind randomized crossover design. The metabolic response to each starch was measured after an overnight fast, in an acute 6 h study, before and after 14 d of daily consumption of 75 g test starch. During each acute study, blood samples were taken at 15 min intervals for the first 2 h and at 30 min intervals for the remaining 4 h. Breath 13CO2 enrichment was measured at the same time points and indirect calorimetry was performed for 20 min every 40 min immediately before and throughout the study. Significantly more rapid, greater changes in postprandial plasma glucose, NEFA and serum insulin concentrations were observed after consumption of the rapidly digestible starch. Breath 13CO2 output over the first 3-4 h rose rapidly then began to decline following consumption of the rapidly digestible starch, but plateaued for the slowly digestible starch. The 14 d adaptation period did not affect any of the glycaemic or lipaemic variables but there was a reduction in postprandial plasminogen activator inhibitor-1 concentrations. These data confirm that starches characterized as predominantly rapidly digestible versus slowly digestible by the Englyst procedure provoke distinctly different patterns of metabolism postprandially.

Adult↗
PubMed2005

Impact of physical activity on intestinal cancer development in mice.

Observational epidemiology supports the hypothesis that variation in diet and other lifestyle exposures accounts for a large part of the variation in incidence of colorectal cancer (CRC). Physical inactivity is associated strongly with enhanced CRC risk, but no human intervention studies have shown causality. This paper reviews data from all available studies of the effects of exercise interventions on intestinal neoplasia using rat and mouse models. All 5 published studies of effects of increased physical activity (both forced and voluntary) using carcinogen-treated rat models show strong protection against CRC by greater physical activity. In contrast, there is little convincing evidence of reduced intestinal neoplasia after increased physical activity in the 3 published studies using Apc(Min) mice (which develop multiple intestinal polyps spontaneously) although the nature and amounts of physical activity imposed in rats and mice were similar. Major differences in protocol between the 2 groups of studies are that the rat studies were much longer (at least 20 wk and in most cases 38 wk compared with < or =9 wk for the mouse studies) and the primary endpoint was colorectal carcinoma (rats) rather than small bowel adenomas (mice). The epidemiological evidence for protection against adenoma formation by increased physical activity is weaker than that for carcinoma. The limited evidence available suggests that, compared with rats, mice may show a greater compensation for energy expenditure in exercise through reduction in nonexercise physical activity, thus ameliorating effects. The resulting smaller effects on body weight and body fatness may limit changes in intestinal neoplasia in Apc(Min) mice.

1,2-Dimethylhydrazine↗
PubMed2004

The biological revolution - towards a mechanistic understanding of the impact of diet on cancer risk.

There is strong epidemiological evidence to show that differences in diet explain a significant proportion of the variation in cancer incidence worldwide. However, because of the complex nature of eating behaviour and the chemical heterogeneity of foods, it remains very difficult to ascertain which aspects of diet, in what quantities and over what time-frames are responsible for modifying risk. In addition, there are few dietary intervention studies demonstrating reduction in cancer risk. Much faster progress has been made in understanding the biological basis of cancer. It is now clear that damage to the genome resulting in aberrant expression of genes (principally suppression of tumour suppressor genes (TSGs) and inappropriate expression of oncogenes) is fundamental to tumorigenesis. It is also becoming clear that much of the inter-individual variation in cancer experience is due to differences in the amount of damage experienced and/or the capacity to repair that damage. Both of these processes are influenced strongly by dietary factors and by genetic predisposition (polymorphisms in the requisite genes). It is possible that understanding diet:gene interactions in DNA damage and in repair will not only explain much of the inter-individual variation in risk but also offer opportunities to design better dietary intervention studies aimed at chemoprevention. The Human Genome maps and the SNPs databases, together with the rapid development of tools suitable for investigating genetic and epigenetic changes in small tissue biopsies provide the means to begin to test hypotheses about the mechanisms by which diet influences cancer risk directly in human subjects. This is likely to form a significant component of the emerging science of nutrigenomics.

Anticarcinogenic Agents↗
PubMed2004

Assessing the survival of transgenic plant DNA in the human gastrointestinal tract.

The inclusion of genetically modified (GM) plants in the human diet has raised concerns about the possible transfer of transgenes from GM plants to intestinal microflora and enterocytes. The persistence in the human gut of DNA from dietary GM plants is unknown. Here we study the survival of the transgene epsps from GM soya in the small intestine of human ileostomists (i.e., individuals in which the terminal ileum is resected and digesta are diverted from the body via a stoma to a colostomy bag). The amount of transgene that survived passage through the small bowel varied among individuals, with a maximum of 3.7% recovered at the stoma of one individual. The transgene did not survive passage through the intact gastrointestinal tract of human subjects fed GM soya. Three of seven ileostomists showed evidence of low-frequency gene transfer from GM soya to the microflora of the small bowel before their involvement in these experiments. As this low level of epsps in the intestinal microflora did not increase after consumption of the meal containing GM soya, we conclude that gene transfer did not occur during the feeding experiment.

Base Sequence↗
PubMed2004

Longitudinal dietary change from adolescence to adulthood: perceptions, attributions and evidence.

Dietary patterns and change in eating habits are influenced by multiple factors from an individual's internal and external environment. A longitudinal dietary survey study provided quantitative evidence of dietary change and investigated factors influencing dietary change from adolescence to adulthood, using sociodemographic data and participants' own perceptions of, and attributions for, their dietary change. Longitudinal dietary data were obtained in 1980 and 2000 (average age 11.6 and 32.5 years, respectively). Two questionnaires (2000) and 2 x 3-day food diaries (1980 and 2000) were collected from 198 participants. Foods consumed were assigned to one of the five food groups from The Balance of Good Health (a UK food guide). Questionnaire responses were used to examine how subjects perceived their own dietary change and the factors to which they attributed such change. Six key factors were identified from the questionnaire: parents, partners, children, nutritional awareness, employment and lack of time. Demographic and key factors were associated with degree of change in intake. The complex process of change in food consumption can be linked with an individual's attributions for change.

Adult↗
PubMed2004

Emerging diet-related surrogate end points for colorectal cancer: UK Food Standards Agency diet and colonic health workshop report.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating emerging diet-related surrogate end points for colorectal cancer (CRC). The workshop aimed to overview current research and establish priorities for future research. The workshop considered that the validation of current putative diet-related surrogate end points for CRC and the development of novel ones, particularly in the emerging fields of proteomics, genomics and epigenomics, should be a high priority for future research.

Biomarkers, Tumor↗
PubMed2004

Starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation in rats treated with the alpha-glucosidase inhibitor acarbose.

Acarbose (Glucobay; Bayer) is an alpha-glucosidase inhibitor used to treat diabetes and which may have a role in the prevention of type 2 diabetes. The present study investigated the effects of acarbose treatment on the site and extent of starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation. Eighteen young male Wistar rats were fed "Westernised" diets containing 0, 250 and 500 mg acarbose/kg (six rats/diet) for 21 d. For most variables measured, both acarbose doses had similar effects. Acarbose treatment suppressed starch digestion in the small bowel but there was compensatory salvage by bacterial fermentation in the large bowel. This was accompanied by a substantial hypertrophy of small- and large-bowel tissue and a consistent increase in crypt width along the intestine. Caecal total SCFA pool size was increased more than 4-fold, with even bigger increases for butyrate. These changes in butyrate were reflected in increased molar proportions of butyrate in blood from both the portal vein and heart. There was little effect of acarbose administration on crypt-cell proliferation (significant increase for mid-small intestine only). This is strong evidence against the hypothesis that increased fermentation and increased supply of butyrate enhances intestinal mucosal cell proliferation. In conclusion, apart from the increased faecal loss of starch, there was no evidence of adverse effects of acarbose on the aspects of large-bowel function investigated.

Acarbose↗