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Susceptibility of transgenic mice carrying human prototype c-Ha-ras gene in a short-term carcinogenicity study of vinyl carbamate and ras gene analyses of the induced tumors.

To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injection of 60 mg of vinyl carbamate (VC)/kg body weight or saline (vehicle control) and monitored for 16 wk without further treatment. At necropsy, grossly visible tumors were fixed for histopathologic diagnosis and, when of sufficient size, portions were frozen for subsequent molecular analysis. Nine of 31 male and nine of 29 female Hras2 mice treated with VC died within 16 wk as a result of lung tumor burden. At the termination of the study, lung tumors (alveolar-bronchiolar epithelial neoplasms and hemangiosarcomas) and focal alveolar-bronchiolar hyperplasias were present in both sexes of Hras2 and non-Tg mice treated with VC; there were significantly more proliferative lung lesions in Hras2 than non-Tg mice. Splenic hemangiosarcomas and squamous cell tumors of the forestomach were induced in male and female VC-treated Hras2 mice but not in VC-treated non-Tg mice. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing of the induced lung tumors revealed point mutations at codon 61 of the transgene in two of 29 lung tumors (one of 16 in males and one of 13 in females) from VC-treated Hras2 mice; no mutations in murine Ki-ras were found in these tumors. Point mutations at codons 12 and 61 of the murine Ki-ras gene were observed, however, in one of 10 and six of 10 lung tumors respectively, from VC-treated non-Tg mice. These findings indicate that Hras2 mice are highly sensitive to pulmonary neoplasms and splenic and lung hemangiosarcomas after treatment with VC. The molecular analyses suggest that point mutations of the transgene and the murine Ki-ras gene do not play a major role in VC induction of pulmonary neoplasms in these transgenic mice.

Adenocarcinoma, Bronchiolo-Alveolar↗

Risk of breast cancer among Greek women in relation to nutrient intake.

A case-control study of the role of diet in the cause of breast cancer was conducted in Athens, Greece. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12-month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion size for each specified food item by the frequency that the food was used per month and summing these estimates for all food items. Cases reported significantly less frequent consumption of vitamin A after controlling for total caloric intake, potential external confounding variables and other nutrients associated with breast cancer risk. The odds ratio estimated for consumption of vitamin A equal to the value of the 90th centile versus consumption equal to the value of the 10th centile was 0.46 with 90% confidence limits 0.26-0.82. There was no evidence that high intake of dietary fat increases the risk of breast cancer.

Breast Neoplasms↗

Obesity and metabolic efficiency.

Obesity has a strong genetic component, which should be viewed as a predisposition only if certain environmental factors are present. Impaired regulation of both sides of the energy balance equation plays a role in the propensity to gain weight and develop obesity. Overeating may be induced in susceptible individuals by high dietary fat content, large portion sizes and low meal frequency. Increased metabolic efficiency in the form of a low resting metabolic rate has been identified in pre- and post-obese subjects, and the impact on total energy expenditure may be amplified by a low level of physical activity. A low thermic effect of food has been shown not to be a risk factor for weight gain, and post-obese subjects have a normal thermic effect of food. A genetically determined enhanced metabolic efficiency during overfeeding has been reported to contribute to fat gain. The heterogeneous nature of obesity indicates that different mechanisms, such as changes in the partitioning of fat (due to lipoprotein lipase activity, fat oxidative muscle enzymes) and carbohydrate, and an altered responsiveness of the sympathoadrenal system and thyroid hormones to a positive energy balance, seem to be involved.

Body Temperature Regulation↗

Diet, reproductive factors and lung cancer risk among Chinese women in Singapore: evidence for a protective effect of soy in nonsmokers.

The factors associated with risk of lung cancer among nonsmokers have not been fully elucidated, but dietary factors have consistently been shown to play a role. Chinese women are unique in having a high incidence of lung cancer despite a low smoking prevalence. This population is also known to have a high intake of soy, a dietary source of phytoestrogens. We conducted a hospital-based case-control study among Singapore Chinese women, comprising 303 cases and 765 age-matched controls, of whom 176 cases and 663 controls were lifetime nonsmokers. Data on demographic background, reproductive factors and dietary intake of fruit, vegetables and soy foods were obtained by in-person interview. We observed an inverse association between intake of total, cruciferous and non-cruciferous vegetables and risk of lung cancer among smokers. Although smokers in the highest tertile of fruit intake also had a lower risk, this was not statistically significant. Higher intake of soy foods significantly reduced risk of lung cancer among lifetime nonsmokers, but not among smokers. When soy isoflavonoid intake in mg/week was computed based on frequency and portion size of intake of eight common local soy foods, the adjusted OR among nonsmokers for the highest tertile compared to the lowest was 0.56, 95% CI 0.37-0.85 (p for trend <0.01). Fruit intake was also significantly associated with reduced lung cancer risk among nonsmokers, but the effect was not significant after adjustment for soy intake. On the other hand, soy intake remained an independent predictor of risk after controlling for fruit intake. Reproductive effects were also primarily confined to lifetime nonsmokers, among whom having 3 or more livebirths (adjusted OR 0.65, 0.44-0.96) and a menstrual cycle length of more than 30 days (OR 0.46, 0.25-0.84) accorded a significantly reduced risk of lung cancer. Place of birth was significantly associated with risk among nonsmokers (OR 2.6, 1.7-3.9 for China-born vs. local born) but not among smokers. When analysis was restricted to nonsmokers with adenocarcinomas, the dietary effects were consistent or enhanced. On stepwise regression, soy intake and cycle length emerged as the independent dietary and reproductive predictors of lung cancer risk in nonsmokers. These findings are consistent with other evidence suggesting an involvement of estrogen-related pathways in lung cancer among non-smoking women.

Adult↗

A case-control study of diet and breast cancer in Argentina.

A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and whole-milk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and beta-carotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer.

Argentina↗

The role of fat, animal protein and some vitamin consumption in breast cancer: a case control study in southern France.

The role of the consumption of fat, animal protein and vitamins on breast-cancer risk was investigated in a hospital-based case-control study of 924 patients (409 cases and 515 controls) in Montpellier (France). A dietary history questionnaire, administered by interview, comprising 55 key food items as well as beverage consumption, and including food frequencies and portion sizes, was used to measure the intake of total fat and its constituents, animal protein, retinol, beta-carotene, vitamin E and alcohol consumption. The questionnaire also elicited information on relevant medical history and personal characteristics. All food items which showed significantly elevated odds ratio (high-fat cheese, desserts and chocolate and processed pork meat) in a multivariate analysis contained a high proportion of animal fat. This is reflected in the nutrient analysis, which showed a significant linear trend as well as an elevated odds ratio for the highest tertile of consumption of total fat [OR3 = 1.6 (1.1-2.2)], animal fat [OR3 = 1.6 (1.1-2.2)], saturated fat [OR3 = 1.9 (1.3-2.6)] and mono-unsaturated fat [OR3 = 1.7 (1.2-2.5)]. For post-menopausal women, there is a particularly strong association with saturated fat [OR3 = 3.3 (1.4-7.8)] in a multivariate analysis including all other significant nutrients. There is no evidence of an increase of risk with the intake of animal protein and no evidence of risk reduction with increased consumption of vegetables, beta-carotene or vitamin E. Along with some recent studies, our results give support to the hypothesis that dietary fat is a risk factor in breast carcinogenesis.

Adult↗

Nutritional factors in colorectal cancer risk: a case-control study in Majorca.

The relationship between energy intake, selected nutrients and colorectal cancer was investigated in the population of Majorca, a Spanish island in the Mediterranean basin. A population-based case-control study using food frequency questionnaires was conducted during the period 1984-1988 and included 286 cases of colorectal cancer, 295 population controls and 203 hospital controls. Food composition tables and ad-hoc estimates of portion sizes were used to derive intake estimates of 29 nutrients and of total calories. Relative risks were calculated for quartiles of consumption of each specific nutrient after adjustment for total calorie intake. Colorectal cancer was found associated with dietary intake of total calories (RRs = 1.0, 1.6, 1.6, 2.6) and cholesterol (RRs = 1.0, 0.9, 1.7, 1.7) and a protective effect was associated with the intake of fibre from legumes (pulses) and folic acid. The associations and the trends were statistically significant. Among the main energy-supplying nutrients, after adjustment for calories from other sources, increased risks were found for protein (RRs = 1.0, 1.1, 1.7, 2.5), notably animal protein, and carbohydrates (RRs = 1.0, 1.5, 1.4, 2.2), whereas no effects were found for increased consumption of lipids or saturated fats.

Case-Control Studies↗

Colon cancer in Argentina. II: Risk from fibre, fat and nutrients.

A case-control study has been conducted to investigate the relationship between total energy intake, fibre and nutrients and colon cancer in Argentina. Cases are 110 newly diagnosed patients from 10 hospitals between 1985 and 1986. Two neighbourhood controls per case were matched on age, sex and place of residence. The intake of calories, fibre and nutrients was estimated from the information collected on food consumption during the 5-year period up to 6 months prior to interview of subjects, based on a pilot study and standard portion sizes in Argentina. In conditional regression models, dietary fibre is highly protective (odds ratio (OR) = 0.07 per 19.02 g/day; 95% confidence interval (CI): 0.02 to 0.25) and total energy intake increases risk (RR = 1.82 per 1000 kcal/day; 95% CI: 1.20 to 2.77), each with adjustment for the other. Analysis of caloric components (fat, protein and carbohydrates) reveals that carbohydrates are the most important factor driving the total energy effect. Other nutrients make little apparent contribution to risk.

Adult↗

Diet and ovarian cancer: a case-control study in Greece.

In a hospital-based case-control study of common malignant epithelial tumors of the ovary, conducted in Athens (1989-1991), 189 cases were compared with 200 hospital visitor controls. Personal interviews were conducted in all cases and diet was ascertained through a semi-quantitative food frequency questionnaire. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a typical portion size for each specified food item by the frequency at which the food was consumed per month and summing these estimates for all food items. Data were analyzed using logistic regression, controlling for non-dietary confounding factors, total energy intake and, among nutrients, mutual confounding influences. Adjusted odds ratios (rate ratios) for ovarian cancer, associated with particular nutritional variables, were expressed in terms of increments approximately equal to the standard deviations of (the residual of) the respective nutrients, on a daily basis. The adjusted odds ratios (and 95% confidence intervals) were 0.80 (0.65-0.99) for mono-unsaturated fat and 0.73 (0.61-0.87) for crude fiber. No substantial, statistically significant or consistent independent associations were noted for total energy, total protein, saturated fat, polyunsaturated fat, dietary cholesterol, total carbohydrates, sucrose, vitamin C, vitamin A, riboflavin or calcium. These associations, if causal, could explain to some extent the relatively low incidence of ovarian cancer in Greece and other Mediterranean countries as well as the increasing incidence trends noted in these countries during the last few decades.

Adult↗

Temperature sex determination in the European sea bass, Dicentrarchus labrax (L., 1758) (Teleostei, Perciformes, Moronidae): critical sensitive ontogenetic phase.

The temperature sex determination (TSD) mechanism in the European sea bass (Dicentrarchus labrax L.) was studied in respect to: a) the TSD sensitivity during the different developmental stages; and b) the intrapopulation correlation of sex determination with the growth rate up to the end of the TSD-sensitive period. At the stage of half-epiboly, eggs from the same batch were divided into four groups and subjected to different thermal treatments: a) 15 degrees C (G15 group) and b) 20 degrees C (G20 group) up to the middle of metamorphosis stage; c) 15 degrees C up to the end of yolk-sac larval stage and subsequently to 20 degrees C (G15-5 group); and d) 15 degrees C up to the end of the preflexion stage and then to 20 degrees C (G15-10 group). At the end of the treatments, size grading was applied and four additional populations were established from the upper (L) and lower (S) size portions of the G15 and G20 populations: G15L, G15S, G20L, and G20S. During the following growing phase, all populations were subjected to common rearing conditions. The sex ratios of each population were macroscopically determined at 190-210 mm mean total length. Female incidence was significantly affected (P < 0.05) by the different thermal treatments: 66.1% in the G15, 47.1% in the G15-10, 37.6% in the G15-5, and 18.1% in the G20 group. In addition, sex ratio was correlated with the growth rate of the fish up to the end of the TSD-sensitive period, with the larger fish presenting a significantly higher (P < 0.01) female incidence than the smaller fish in both thermal regimes tested: 73.1% in G15L vs. 57% in G15S, and 36.6% in G20L vs. 22.5% in G20S group. Results provide, for the first time, clear evidence that the sea bass is sensitive to TSD during all different ontogenetic stages up to metamorphosis, and that sex ratio is correlated with the growth rate of the fish well before the differentiation and maturation of the gonads.

Animals↗

Gender and living alone as determinants of fruit and vegetable consumption among the elderly living at home in urban Nottingham.

Consumption of fruits and vegetables by a sample of 369 elderly people living in Nottingham, England, was analysed in relation to whether or not they were eating five portions a day. Living status was only of significance to men who, if single, consumed 2.66 portions of fruits and vegetables per day compared with an overall mean of 4.1. The salient question is therefore not "Are you living alone?" but " s there a woman in the household?". Those respondents who were older and less educated ate less vegetables and those respondents who had a lower income or social grade ate less fruit. Men were less likely to be able to cook a range of meals, to have had a job that involved cooking or to watch cookery programmes on television. Single men were more likely than single women to say that eating food that was easy to cook and prepare was an important influence on their food choice. Single women on the other hand were more influenced by body image. Finding foods that were the right portion size and easy to open, prepare and cook was more important to single men than married men, as was the amount of money left after paying the bills.

Aged↗

Reliability and relative validity of fish consumption data obtained in an exposure assessment study among Montreal-area sportfishers.

A two-season exercise was undertaken in 29 high-level sportfish consumers to evaluate the reliability and accuracy of study instruments. Fishers were invited to participate after completing the main study interview (Time 1) in fall 1995 or winter 1996. Over a 4-week period, they provided a nonconsecutive 7-day weighed food record, kept a fish consumption calendar, and responded to a shortened version of the Time 1 instrument at the end of this period (Time 2). A second blood sample (at Time 2) was analyzed for whole blood mercury (Hg) and the omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) in plasma and erythrocytes. Identical questions were compared in the Time 1 and Time 2 instruments. Reported sportfish consumption assessed by the different instruments was subjected to nutrient analysis. Three estimates of exposure to the target substances were derived from the dietary intake estimates and correlated with their respective Time 2 plasma (EPA, DHA) or blood (Hg) values, and with a kinetically derived interval-specific plasma/blood uptake value. Remarkable similarities were observed for the data derived from like questions in the Time 1 and 2 questionnaires in both seasons. However, frank discrepancies between some portion size estimates and measured values may signal cause for concern. The strongest correlations between the Time 2 plasma DHA and EPA, and blood Hg, and the three exposure indices emerged between estimates of retrospective DHA intake and DHA fish calendar values and their corresponding Time 2 plasma levels, and for Hg estimated both retrospectively and from the fish consumption calendar and correlated with Time 2 blood Hg, especially in the winter 1996 dataset. Overall, the results suggest that the main study instrument provides a reliable and relatively accurate indication of sportfishers' fishing practices, species selection, and sportfish consumption habits.

Adult↗

Nutrient intake and cancer of the pancreas: a case-control study in Athens, Greece.

In a hospital-based case-control study of pancreatic cancer conducted in Athens (1991-92), 181 patients with histologically confirmed cancer of the exocrine pancreas were compared with hospital patient controls and hospital visitor controls, individually matched to the cases by hospital, age, gender, and interviewer in a 1:1:1 ratio. All interviews were conducted in person in the respective hospitals. Diet was ascertained through a semiquantitative food-frequency questionnaire. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion-size for each specified food-item by the frequency that the food was used per month, and summing these estimates for all food items. Data were analyzed using conditional logistic regression, controlling for tobacco smoking and total energy intake as well as for mutual confounding influences among nutrients. Adjusted odds ratios (rate ratios) for pancreatic cancer, associated with particular nutritional variables, were expressed per increments approximately equal to the standard deviations of (the residual of) the respective nutrients, on a daily basis. The adjusted odds ratios (OR) and 95 percent confidence intervals (CI) compared with other patient and visitor controls respectively, were: for polyunsaturated fat, OR = 1.32 (CI = 1.07-1.63) and 1.21 (CI = 0.98-1.49); and for crude fibre, OR = 0.80 (CI = 0.64-1.00) and 0.65 (CI = 0.50-0.86). No substantial, statistically significant or consistent, independent associations were noted for total energy, total protein, total fat, saturated fat, monounsaturated fat, dietary cholesterol, total carbohydrates, sucrose, vitamin C, vitamin A, riboflavin, or calcium.

Ascorbic Acid↗

[What do you eat? Food frequency questionnaire for children and adolescents].

In the German Health Survey for Children and Adolescents (KiGGS), which started in May 2003, about 18,000 representatively chosen children and adolescents will be physically examined and interviewed about their health during a period of 3 years. Since nutrition is a main determinant of health, several aspects such as breastfeeding by the mother, dietary behavior, and eating disorders will be determined. In addition to some specific nutrition questions in the general health questionnaire, consumption frequency and portion sizes of the main food groups will be assessed with a newly developed questionnaire. This questionnaire is presented and its advantages and disadvantages are discussed.

Adolescent↗

[Current problems in determining children's nutritional needs].

Meeting children's nutritional needs is of fundamental importance for their immediate and later health, well-being, and performance. Age-adapted reference values of nutrient intake form the basis for analysis of the current situation and for policy planning, but for many nutrients they cannot be precisely defined due to inadequate scientific data. Therefore, such values are often extrapolated from adult reference values based on age-adapted mean body weight or body surface data, although such extrapolation does not reflect age-related physiological changes. There are considerable differences between various expert recommendations, in part also due to differences in definitions and underlying concepts for deriving reference values. Improvements and international harmonization are urgently needed. Nutritional needs of many children and adolescents are not adequately met at present. A particularly obvious indication is the epidemic-like increase of pediatric overweight and obesity, which could result in markedly increased prevalences of later metabolic syndrome, diabetes, and cardiovascular diseases. Contributing to increasing childhood obesity are low physical activity, changing eating culture and behavior, frequent consumption of high-fat foods with high energy density, and increasing portion sizes. Changes are urgently needed and might be achievable with close collaboration between scientists, public institutions, and industry.

Adolescent↗

[EPIC-SOFT a European computer program for 24-hour dietary protocols].

Within the EPIC study (European Prospective Investigation into Cancer and Nutrition) a calibration approach is applied to compare dietary data obtained by food frequency questionnaires from 9 European countries. A software for 24-h recalls was developed as the calibration instrument by the International Agency for Research on Cancer (IARC) in collaboration with all national EPIC centers. This computer program, called EPIC-SOFT, is an interview-based dietary assessment instrument that allows one to obtain a very detailed description and quantification of foods, recipes, and supplements consumed in the course of the preceding day. Probing questions and entering consumed foods in chronological order support the respondent's memory. The standardized structure prescribes--on the food group level--possibilities of description and quantification of food items to choose from. Quantification of consumed foods is supported by the EPIC-SOFT picture book that comprises colored photographs of foods in different portion sizes. The software provides an automatic coding of food items and recipe ingredients as well as calculation of nutrient intake. EPIC-SOFT is characterized by the obtained standardization of dietary data within Europe, a large number of available foods and recipes, and a very detailed description of consumed foods. Currently, EPIC-SOFT is one of the few dietary instruments providing comparable nutritional data within Europe.

Calibration↗

Validation of a self-administered 3-day estimated dietary record for use in the elderly.

AIM OF THIS STUDY: was to assess the validity of a 3-day estimated dietary record, especially developed for the longitudinal study on nutrition and health status in an aging population (aged > or = 60 years) in Giessen, Germany. METHODS: The dietary record comprises 146 food items. Portion sizes of the foods consumed were estimated by means of household measures and corresponding dimensions. The validity of the dietary record was evaluated by means of nitrogen excretion in the 24 h urine in 14 women and 9 men, and by comparing energy intake and basal metabolic rate determined by indirect calorimetry in 238 women and 105 men. RESULTS: Neither in women nor in men were any differences found between calculated nitrogen intake (13.4 +/- 2.2 g and 15.0 +/- 2.0 g, respectively) and nitrogen excretion (12.9 +/- 2.1 g and 15.7 +/- 3.0 g, respectively). The ratio between reported energy intake and basal metabolic rate was 1.62 +/- 0.46 in women and 1.53 +/- 0.46 in men. Regarding energy intake, 7.6% of the females and 16.2% of the males were classified as under-reporters. They show a significantly higher body weight and BMI than the adequate reporters. CONCLUSION: The results have proved the new 3-day estimated dietary record as suitable to determine energy and nutrient supply of the elderly.

Aged↗

Calcium balance in young adults on a vegan and lactovegetarian diet.

For people in Western countries, the vegan diet has the advantage of low energy intake, but the calcium status of this strictly plant-based diet is still unclear. The aim of this study was to determine the calcium balance of individuals on a vegan diet in comparison with a lactovegetarian diet in a short-term investigation. Seven women and one man, ranging in age from 19 to 24 years, received during the first 10 days a vegan diet based on plant foods and calcium-rich mineral water and a lactovegetarian diet during the following 10 days. Portion size was adapted to the subjects' individual energy requirements. Calcium status was assessed by means of calcium intake in food and calcium output in feces and urine as measured by flame atomic absorption spectrophotometry. In addition, deoxypyridinoline was measured in urine as a marker of bone resorption. The results show a significantly smaller daily calcium intake with an average of 843 +/- 140 mg in the vegan versus 1322 +/- 303 mg in the lactovegetarian diet. Apparent calcium absorption rates were calculated as 26% +/- 15% in the vegan and 24% +/- 8% in the lactovegetarian group (NS). The calcium balance was positive both in the vegan diet (119 +/- 113 mg/day) and in the lactovegetarian diet (211 +/- 136 mg/day) (NS). Deoxypyridinoline excretion showed no significant difference between the two diets (105 +/- 31 and 98 +/- 23 nmol/day). The present results indicate that calcium balance and a marker of bone turnover are not affected significantly when calcium is provided either solely by plant foods or by a diet including dairy products, despite the significantly different calcium intake levels in the diets. We conclude that a well-selected vegan diet maintains calcium status, at least for a short-term period.

Adult↗