Psychiatry has been, among medical disciplines, the one showing the highest conflict between a «positivist» model and the «hermeneutic» tradition. In particular, in recent years several authors have suggested that both the scientific method and a scientific mentality should be introduced in psychiatric practice and research. They claim that criteria like a strong correlation among clearly defined signs and symptoms, a high predictive value towards the outcome and therapeutical response, and a clearly defined relationship between the symptoms and etiology are necessary to accept a diagnositc entity. Since in the case of e.g. schizofrenia such requirements are not met, some authors even suggest that the concept of schizofrenia should be abandoned. The present paper aims to show that such problems are not unique to mental disease, but are common to several branches of medicine. For example, the definition and classification of cancer follow a «polythetic» criterion which is similar to the concept of «family resemblances». Also, diagnostic reproducibility is often low in other medical disciplines. The paper examines how such methodological problems could be dealt with using the tools of epidemiology.

Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case–control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.

Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north–south gradient. Vitamin B2 concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (Ptrend< 0·001). Vitamin B6 concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (Ptrend< 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.

Folate plays an important role in the synthesis and methylation of DNA as a cofactor in one-carbon metabolism. Inadequate folate intake has been linked to adverse health events. However, comparable information on dietary folate intake across European countries has never been reported. The objective of the present study was to describe the dietary folate intake and its food sources in ten countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cross-sectional analysis was conducted in 36 034 participants (aged 35–74 years) who completed a single 24 h dietary recall using a computerised interview software program, EPIC-Soft® (International Agency for Research on Cancer, Lyon). Dietary folate intake was estimated using the standardised EPIC Nutrient DataBase, adjusted for age, energy intake, weight and height and weighted by season and day of recall. Adjusted mean dietary folate intake in most centres ranged from 250 to 350 μg/d in men and 200 to 300 μg/d in women. Folate intake tended to be lower among current smokers and heavier alcohol drinkers and to increase with educational level, especially in women. Supplement users (any types) were likely to report higher dietary folate intake in most centres. Vegetables, cereals and fruits, nuts and seeds were the main contributors to folate intake. Nonetheless, the type and pattern of consumption of these main food items varied across the centres. These first comparisons of standardised dietary folate intakes across different European populations show moderate regional differences (except the UK health conscious group), and variation by sex, educational level, smoking and alcohol-drinking status, and supplement use.

In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0·02), vitamin E (P = 0·04) and alcohol (P = 0·03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0·03, 0·04, and 0·03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.

At least six types of gene–environment interactions (GEI) have been proposed (Kouhry and Wagener, 1993) In the first type, neither the environmental exposure (EE) nor the genetic risk factor (GRF) have any effect by themselves, but interaction between them causes disease. This is the case of phenylalanine exposure and the phenylketonuria genotype. Type 2 is a situation in which the GRF has no effect on disease in the absence of exposure, but exacerbates the effects of the latter. This is the most important type of GEI in relation to metabolic susceptibility genes and human carcinogenesis. The third type is the converse of the second (EE is ineffective per se, but enhances the effect of GRF). Type 4 occurs when both EE and GRF increase the risk for disease, but the combination is interactive or synergistic: an example is the interaction between Xeroderma Pigmentosum and UV radiation. Types 5 and 6, according to the classification proposed by Kouhry, refer to cases in which the GRF is protective.

The model of GEI that is emerging as the most important in chemical carcinogenesis refers to metabolic susceptibility genes. The general population can be divided into subgroups depending on their susceptibility to the action of carcinogens, based on their ability to metabolize such compounds to electrophilic, reactive metabolites (which form adducts with DNA), or, respectively, electrophobic metabolites that are excreted. The present contribution is a short review of the relevant literature, with particular emphasis on some polymorphisms involved in dietary exposures. In addition, the practical implications of genetic testing in this field are discussed.

A diet rich in fruit and vegetables can be effective in the reduction of oxidative stress, through the antioxidant effects of phytochemicals and other mechanisms. Protection against the carcinogenic effects of chemicals may also be exerted by an enhancement of detoxification and DNA damage repair mechanisms. To investigate a putative effect of flavonoids, a class of polyphenols, on the regulation of the gene expression of DNA repair and metabolic genes, a 1-month flavonoid-rich diet was administered to thirty healthy male smokers, nine of whom underwent gene expression analysis. We postulated that tobacco smoke is a powerful source of reactive oxygen species. The expression level of twelve genes (APEX, ERCC1, ERCC2, ERCC4, MGMT, OGG1, XPA, XPC, XRCC1, XRCC3, AHR, CYP1A1) was investigated. We found a significant increase (P < 0·001) in flavonoid intake. Urinary phenolic content and anti-mutagenicity did not significantly change after diet, nor was a correlation found between flavonoid intake and urinary phenolic levels or anti-mutagenicity. Phenolic levels showed a significant positive correlation with urinary anti-mutagenicity. AHR levels were significantly reduced after the diet (P = 0·038), whereas the other genes showed a generalized up regulation, significant for XRCC3 gene (P = 0·038). Also in the context of a generalized up regulation of DNA repair genes, we found a non-significant negative correlation between flavonoid intake and the expression of all the DNA repair genes. Larger studies are needed to clarify the possible effects of flavonoids in vivo; our preliminary results could help to better plan new studies on gene expression and diet.

Dietary habits play an important role in healthy ageing. We have investigated the role of dietary patterns on overall mortality in a large series of Italian elderly, recruited in five EPIC cohorts in Northern (Varese and Turin), Central (Florence) and Southern Italy (Naples and Ragusa).A total of 5611 subjects (72·6 % women) aged 60 years or older, enrolled in 1993–1998, were prospectively followed (median 6·2 years), with 152 deaths (98 women). Four major dietary patterns were identified by using an exploratory factor analysis based on dietary information collected at enrolment. The associations between these dietary patterns and overall mortality were evaluated by Cox models adjusted for potential confounders. The ‘Olive Oil & Salad’ pattern, characterised by a high consumption of olive oil, raw vegetables, soups and poultry, emerged as being inversely associated with overall mortality in both crude and adjusted models. After adjustment for gender, age and caloric intake, overall mortality was reduced by approximately 50 % in the highest quartile and a significant trend emerged (P = 0·008). This association persisted after adjusting for several additional confounders (hazard ratio (HR) 0·50; 95 % CI 0·29, 0·86; P for trend =  0·02). An association of the ‘Pasta & Meat’ pattern (characterised by pasta, tomato sauce, red meat, processed meat, added animal fat, white bread and wine) with increased overall mortality was also suggested, but only for the highest quartile in a multivariate model. Dietary recommendations aimed at the Italian elderly population should support a dietary pattern characterised by a high consumption of olive oil, raw vegetables and poultry.