Nutrigénomique: cas pour un terrain commun à la maladie cardiovasculaire et au cancer

The border between health and disease is often set by a complex equilibrium between two elements genetics on one hand, lifestyle on the other, To know it better, means to give new weapons, often crucial, in the hands of the doctors and their patients. It also means to adjust therapies, to find out which drug is good for a patient and which prevention strategy will work better for him/her. Nutrigenomics is an approach to individualize or personalize food and nutrition, and ultimately health, by tailoring the food to the individual genotype. In this review, we present the interaction between certain genetic polymorphisms and diet and increased cardiovascular or cancer risk. It is, indeed, now clear that a large number of bioactive food components may provide risk or protection at several stages of both atherosclerosis and cancer formation processes. We are giving here few examples of gene-food interactions relevant for both the risk of cardiovascular disease and cancer, since a common soil could exist in the genesis of cardiovascular disease and of some types of cancer (mainly gastrointestinal tract and hormonedependent).     

Nutrigenomics: integrating genomic approaches into nutrition research

It has been suggested that the supermarket of today will be the pharmacy of tomorrow. Such statements have been derived from recognition of our increasing ability to optimize nutrition, and maintain a state of good health through longer periods of life. The new field of nutrigenomics, which focuses on the interaction between bioactive dietary components and the genome, recognizes that current nutritional guidelines may be ideal for only a relatively small proportion of the population. There is good evidence that nutrition has significant influences on the expression of genes, and, likewise, genetic variation can have a significant effect on food intake, metabolic response to food, individual nutrient requirements, food safety, and the efficacy of disease-protective dietary factors. For example, a significant number of human studies in various areas are increasing the evidence for interactions between single nucleotide polymorphisms (SNPs) in various genes and the metabolic response to diet, including the risk of obesity. Many of the same genetic polymorphisms and dietary patterns that influence obesity or cardiovascular disease also affect cancer, since overweight individuals are at increased risk of cancer development. The control of food intake is profoundly affected by polymorphisms either in genes encoding taste receptors or in genes encoding a number of peripheral signaling peptides such as insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors. Total dietary intake, and the satiety value of various foods, will profoundly influence the effects of these genes. Identifying key SNPs that are likely to influence the health of an individual provides an approach to understanding and, ultimately, to optimizing nutrition at the population or individual level. Traditional methods for identification of SNPs may involve consideration of individual variants, using methodologies such as restriction fragment length polymorphisms or quantitative real-time PCR assays. New developments allow identification of up to 500,000 SNPs in an individual, and with increasingly lowered pricings these developments may explode the population-level potential for dietary optimization based on nutrigenomic approaches.     

Differentiation of human pre-adipocytes by recombinant adiponectin

Obesity has become a global health problem and it is linked to a higher risk of diseases and metabolic disorders such as diabetes, cardiovascular disease, and cancer. The adipose tissue plays an important role in monitoring and controlling whole-body metabolism by secreting a variety of bioactive molecules such as adiponectin. Deficiencies of this hormone can cause type II diabetes and cardiovascular disease both in mice and in humans. Therefore, adiponectin is an attractive molecule to use in human therapy, particularly in a recombinant form. The source of recombinant adiponectin could be the expression of full-length adiponectin either in Escherichia coli, or in baculovirus. In this work we express and purify human adiponectin in both systems. The adiponectin produced by baculovirus was found to be 10 times more active as far as oligomerization and human pre-adipocyte differentiation are concerned, when compared with adiponectin produced by E. coli. We presume that adiponectin expressed in baculovirus has post-translation modifications not made by bacteria which may be responsible for these differences in activity. This renders adiponectin produced by baculovirus a better candidate for the treatment of type II diabetes and cardiovascular disease.     

Correlations of insulin resistance and neoplasms

Insulin resistance is a worldwide risk factor for the two most dangerous human disease groups; namely, for cardiovascular lesions and malignancies. The insulin resistance syndrome have five basic criteria: hyperglycemia, visceral obesity, elevated serum triglyceride level, low HDL-cholesterol level (dyslipidemia) and hypertension. Each of these criteria alone are risk factors for cancer, and they mean together a multiple risk. Insulin resistance of the liver, skeletal muscles, and fatty tissue leads to a reactive hyperinsulinemia by the increased secretory activity of the beta-cells. Insulin has diverse metabolic effects, and at the same time is a growth factor. It enhances the production and mitogenic activity of other, insulin-like growth factors, and leads to pathological cell proliferation. In the uncompensated phase of insulin resistance hyperglycemia appears, which promotes tumor genesis by several pathways. The elevated serum glucose level is advantageous for the increased DNA synthesis of the tumor cells. It provokes deliberation of free radicals, which will cause derangement of both the DNA and the enzymes having a role in the repair mechanisms. Hyperglycemia leads to a nonenzymatic glycation of protein structures, and the glycated products enhance the deliberation of free radicals, cytokines and growth factors. Insulin resistance means an enhanced risk for breast, pancreas, liver, colon, bladder, prostate and oral cavity cancers. The moderately increased fasting glucose level is also a risk factor for breast, stomach and colon cancers, even without manifestation of type 2 diabetes. Insulin resistance promotes tumor progression as well. In cancer patients with hyperglycemia or type 2 diabetes, the rate of tumor recurrence, metastatic spread and fatal outcome is higher as compared with the tumor patients without metabolic disease. The correlation between insulin resistance and tumor promotion reveals new possibilities in the prevention and treatment of cancer. The healthy diet, physical activity and weight loss increase insulin sensitivity, and decrease the risk for both cardiovascular diseases and malignancies.     

The vascular implications of post-prandial lipoprotein metabolism

Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Assessment is usually made in the fasting state, and particular attention is directed towards the measurement of the cholesterol content of both the low and high-density lipoprotein fractions. By comparison, a massive amount of lipid fluxes through the intra-vascular compartment during the post-prandial period. This has led to the hypothesis that atherosclerosis could be partially, or even predominantly, due to the pathological effects of this flux of post-prandial lipoproteins on the vessel wall. This justifies efforts to systematically study the relationship between the lipoprotein responses to food (particularly fat) ingestion and cardiovascular disease or its surrogate markers. This review will consider the mechanisms by which post-prandial metabolism might affect the risk of CVD. It will examine the evidence for and against such an association. It will also consider the practical and methodological issues that are likely to determine the future utility of post-prandial lipoprotein assessment.     

Does microbiological testing of foods and the food environment have a role in the control of foodborne disease in England and Wales?

This review looks at the contribution of microbiological sampling to the safety of retail foods in England and Wales. It compares sampling methods available and assesses the value of testing as part of outbreaks of foodborne disease, as part of routine management by local authorities, as part of work done or commissioned by the food industry, and as part of research. It confirms that microbiological testing has a role during outbreaks as it makes a significant contribution to help identify foods and other areas of greatest risk for future study. The review suggests that routine testing by local authorities is often of limited use and could be improved by more targeted surveillance. Testing could be better used to validate primary control methods, such as Hazard Analysis and Critical Control Point (HACCP) system. Any public health benefit from testing in the food industry is often restricted by client confidentiality. Microbial research on foods is important as it can lead to significant improvements in safety. Current microbiological methods are slow and, in future, rapid molecular methods may make an even bigger contribution to the control of foodborne disease.     

Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased?

OBJECTIVE--To quantify the effect of selection of relatively healthy women in studies reporting reduced relative risk for cardiovascular disease in postmenopausal women taking hormone replacement therapy. DESIGN--Review of the follow up studies reported in three recent meta-analyses to determine the effect of oestrogen therapy on both total cancer and cardiovascular disease. The same standard statistical methods as in the original analyses were used. MAIN OUTCOME MEASURES--Relative risks of total cancer and cardiovascular disease. RESULTS--In most of the follow up studies the relative risk for total cancer was below 1. The studies that showed the largest reduction in cardiovascular disease also showed the largest reduction in cancer, indicating a healthy cohort effect. Although heterogeneity within the studies prevented pooling, the best estimate for the protective effect on total cancer was a relative risk of 0.83 among women taking oestrogen (95% confidence interval 0.71 to 0.96), while in the same studies the relative risk for cardiovascular disease was 0.57 (0.50 to 0.64). CONCLUSIONS--Unintended selection of relatively healthy women for oestrogen therapy may have influenced the reported beneficial effect of oestrogen therapy on cardiovascular disease. It is unclear how much of the cardioprotection is due to this selection. Universal preventive hormonal replacement therapy for postmenopausal women is unwarranted at present.     

Socioeconomic status during childhood and health status in adulthood: the Wrocław growth study

It has been widely observed that socioeconomic status (SES) is associated with frequency of cardiovascular disease. Both men and women of low socioeconomic position have increased risk of cardiovascular disease morbidity and premature death. In this study the relationship between SES in childhood, and health status at the age of 50 years was examined. Socioeconomic status in childhood was measured using objective (father's educational level and number of children in the family) and subjective (self-assessed SES in childhood declared in early adulthood) indicators. Data from the Wroclaw Growth Study were completed when subjects were 50 years old, and information concerning health status was added. The results indicated that the objective, universally used measures of SES in childhood such as father's educational level and size of family did not show any essential relationships with health outcomes in adulthood, both for men and women. By contrast, retrospective, self-assessed SES (as better, average or worse as compared with peers) in childhood was significantly associated with the appearance of cardiovascular disease among women aged 50 years. Women who at the beginning of their adult life declared better socioeconomic condition in childhood were significantly healthier at the age of 50 years (OR=3.43; p=0.02). Moreover, this appeared to be independent of BMI, SES and life-style in adulthood. For men, retrospective self-assessed SES showed no relation to health status at the age of 50 years. The gender differences in the relationships between self-assessed SES in childhood and health status in adulthood are explained by possible selective premature mortality among men from lower childhood SES and/or sex differences in cognitive abilities.     

Pharmaco-écho-doppler pénien: méthodologie, critères diagnostiques et indications actuelles dans l’exploration d’une dysfonction érectile

Erectile dysfunction (ED) is a common multifactorial disease, whose organic or mixed origin is currently considered as dominant in men aged 50 years and older. Most ED classified as arterial are linked to endothelial dysfunction in relation to the key factors of cardiovascular risk. ED is an indicator of vascular health in general. It is also a predictor of cardiovascular events, including coronary heart disease. It has also been associated with lower peripheral arterial disease and stroke. The penile doppler ultrasound examination is actually used relatively infrequently in the management of ED, the etiologic factors being considered most often not necessary for the therapeutic management, but also because of the absence of standardization. Nonetheless, large recent studies have shown that the vascular nature of ED, basis on doppler parameters recorded after intracavernous injection of vasoactive drugs, strengthened the predictive value of ED on events and cardiovascular mortality, justifying a highest interest in this test.     

Gastrointestinal microflora,food components and colon cancer prevention

Evidence that the intestinal microbiota is intrinsically linked with overall health, including cancer risk, is emerging. Moreover, its composition is not fixed but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics) and indigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota can also influence both sides of the energy balance equation, namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex complexion deserves greater attention. Overall, a dynamic interrelationship exists between the intestinal microbiota and colon cancer risk, which can be modified by dietary components and eating behaviors.     

Physiological effects of broccoli consumption

Epidemiological studies suggest that broccoli can decrease risk for cancer. Broccoli contains many bioactives, including vitamins C and E, quercetin and kaempferol glycosides and, like other members of the Brassicaceae, several glucosinolates, including glucobrassicin (3-indolylmethyl glucosinolate) and glucoraphanin (4-methylsulphinylbutyl glucosinolate). A key bioactive component responsible for much of this activity may be sulforaphane (1-isothiocyanato-4-methylsulfinylbutane), a hydrolysis product of glucoraphanin. Sulforaphane not only upregulates a number of phase II detoxification enzymes involved in clearance of chemical carcinogens and reactive oxygen species, but has anti-tumorigenic properties, causing cell cycle arrest and apoptosis of cancer cells. The bioequivalency of sulforaphane and whole broccoli have not been fully evaluated, leaving it unclear whether whole broccoli provides a similar effect to purified sulforaphane, or whether the presence of other components in broccoli, such as indole-3-carbinol from glucobrassicin, is an added health benefit. Dietary indole-3-carbinol is known to alter estrogen metabolism, to cause cell cycle arrest and apoptosis of cancer cells and, in animals, to decrease risk for breast cancer. Recent research suggests that both dietary broccoli and the individual components sulforaphane and indole-3-carbinol may offer protection from a far broader array of diseases than cancer, including cardiovascular and neurodegenerative diseases. A common link between these oxidative degenerative diseases and cancer may be aggravation by inflammation. A small body of literature is forming suggesting that both indole-3-carbinol and sulforaphane may protect against inflammation, inhibiting cytokine production. It remains to be seen whether cancer, cardiovascular disease, dementia and other diseases of aging can all benefit from a diet rich in broccoli and other crucifers.     

Exercise, oxidative stress and risk of cardiovascular disease in the elderly. Protective role of antioxidant functional foods

Free radicals and oxidative stress are involved in the pathogenic mechanisms of cardiovascular disease (CVD), diabetes and cancer. Exercise is a useful strategy for preventing CVD but in elderly persons it can enhance oxidative stress, which is why some studies recommend antioxidant supplementation for exercising elderly subjects. This intervention study was performed on 320 elderly subjects following a Geriatric Revitalization Program (GEREPRO) to maintain physical health and reduce CVD risk. GEREPRO was based on regular exercise concurrent with a nutritional antioxidant treatment based on daily intake of a functional antioxidant food, Biofrutas. Sustained exercise (10 months, 3 sessions/week) significantly increased cardiorespiratory fitness and plasma HDL-cholesterol; it reduced some predictors of cardiovascular risk (arterial pressure, LDL-cholesterol, total cholesterol/LDL-C, LDL-C/HDL-C), but significantly enhanced some biomarkers of oxidative stress. Concurrent antioxidant supplementation did not produce any ergogenic effects but, meaningfully, enhanced some positive effects of exercise on physical health and the CDV risk index, and it totally prevented the exercise-induced oxidative stress. Our results show that regular and moderate exercise improves cardiorespiratory function and reduces CVD risk in elderly people, while concurrent antioxidant supplementation modulates oxidative insult during exercise in the elderly and enhances the beneficial effects of exercise.     

Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis

Objective To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia.Design Systematic review and meta-analysis.Data sources Embase and Medline without language restrictions, including papers published between 1960 and December 2006, and hand searching of reference lists of relevant articles and reviews for additional reports.Review methods Prospective and retrospective cohort studies were included, providing a dataset of 3 488 160 women, with 198 252 affected by pre-eclampsia (exposure group) and 29 495 episodes of cardiovascular disease and cancer (study outcomes).Results After pre-eclampsia women have an increased risk of vascular disease. The relative risks (95% confidence intervals) for hypertension were 3.70 (2.70 to 5.05) after 14.1 years weighted mean follow-up, for ischaemic heart disease 2.16 (1.86 to 2.52) after 11.7 years, for stroke 1.81 (1.45 to 2.27) after 10.4 years, and for venous thromboembolism 1.79 (1.37 to 2.33) after 4.7 years. No increase in risk of any cancer was found (0.96, 0.73 to 1.27), including breast cancer (1.04, 0.78 to 1.39) 17 years after pre-eclampsia. Overall mortality after pre-eclampsia was increased: 1.49 (1.05 to 2.14) after 14.5 years.Conclusions A history of pre-eclampsia should be considered when evaluating risk of cardiovascular disease in women. This association might reflect a common cause for pre-eclampsia and cardiovascular disease, or an effect of pre-eclampsia on disease development, or both. No association was found between pre-eclampsia and future cancer.     

Climate change and health with an emphasis on interactions with ultraviolet radiation: a review

Climate change is increasingly recognized as a major risk to human health, and health concerns are assuming more importance in international debates on mitigation and adaptation strategies. Health consequences of climate change will occur through direct and indirect routes, and as a result of interactions with other environmental exposures. Heatwaves will become more common and are associated with higher mortality particularly in the elderly and those with pre‐existing cardiovascular and respiratory illnesses. Warmer ambient temperatures will result in more dehydration episodes and increased risks of renal disease and, through effects on pollen seasons, there may be an increase in allergic disease such as asthma and hayfever. Other adverse effects including on air quality, food safety and security and an expanding distribution of some infectious diseases, including vector‐borne diseases, are postulated. A related but separate environmental exposure is that of ultraviolet radiation (UVR). Interactions between climate change and stratospheric ozone (and the causes of ozone depletion) will cause changes to levels of ambient UVR in the future and warmer temperatures are likely to change sun exposure behaviour. Co‐occurring effects on aquatic and terrestrial ecosystems have potential consequences for food safety, quality and supply. Climate change‐related exposures are likely to affect the incidence and distribution of diseases usually considered as caused by UVR exposure; and changes in UVR exposure will modulate the climate change effects on human health. For example, in some regions warmer temperatures due to climate change will encourage more outdoor behaviour, with likely consequences for increasing skin cancer incidence. Although many of the health outcomes of both climate change and the interaction of climate change and UVR exposure are somewhat speculative, there are risks to over‐ or under‐estimations of health risks if synergistic and antagonistic effects of co‐occurring environmental changes are not considered.     

Human nutrition and food research: opportunities and challenges in the post-genomic era

Sequencing of the human genome has opened the door to the most exciting new era for nutritional science. It is now possible to study the underlying mechanisms for diet-health relationships, and in the near future dietary advice (and possibly tailored food products) for promoting optimal health could be provided on an individual basis, in relation to genotype and lifestyle. The role of food in human evolution is briefly reviewed, from palaeolithic times to modern-day hunter-gatherer societies. The aetiology of 'diseases of modern civilization', such as diabetes, heart disease and cancer, and the effect of changes in dietary patterns are discussed. The risk of disease is often associated with common single nucleotide polymorphisms, but the effect is dependent on dietary intake and nutritional status, and is often more apparent in intervention studies employing a metabolic challenge. To understand the link between diet and health, nutritional research must cover a broad range of areas, from molecular to whole body studies, and is an excellent example of integrative biology, requiring a systems biology approach. The annual cost to the National Health Service of diet-related diseases is estimated to be in excess of 15 billion, and although diet is a key component of any preventative strategy, it is not given the prominence it deserves. For example, less than 1% of the pound 1.6 billion budget for coronary heart disease is spent on prevention. The polygenic and multifactorial nature of chronic diseases requires substantial resources but the potential rewards, in terms of quality of life and economics, are enormous. It is timely therefore to consider investing in a long-term coordinated national programme for nutrition research, combining nutritional genomics with established approaches, to improve the health of individuals and of the nation.     

Vegan diet in physiological health promotion

We have performed a number of studies including dietary interventions and cross-sectional studies on subjects consuming uncooked vegan food called living food (LF) and clarified the changes in several parameters related to health risk factors. LF consists of germinated seeds, cereals, sprouts, vegetables, fruits, berries and nuts. Some items are fermented and contain a lot of lactobacilli. The diet is rich in fiber. It has very little sodium, and it contains no cholesterol. Food items like berries and wheat grass juice are rich in antioxidants such as carotenoids and flavonoids. The subjects eating living food show increased levels of carotenoids and vitamins C and E and lowered cholesterol concentration in their sera. Urinary excretion of sodium is only a fraction of the omnivorous controls. Also urinary output of phenol and p-cresol is lowered as are several fecal enzyme levels which are considered harmful. The rheumatoid arthritis patients eating the LF diet reported amelioration of their pain, swelling of joints and morning stiffness which all got worse after finishing LF diet. The composite indices of objective measures showed also improvement of the rheumatoid arthritis patients during the intervention. The fibromyalgic subjects eating LF lost weight compared to their omnivorous controls. The results on their joint stiffness and pain (visual analogue scale), on their quality of sleep, on health assessment questionnaire and on general health questionnaire all improved. It appears that the adoption of vegan diet exemplified by the living food leads to a lessening of several health risk factors to cardiovascular diseases and cancer. Rheumatoid patients subjectively benefited from the vegan diet which was also seen in serum parameters and fecal analyses.     

Multistate modeling and structure selection for multitype recurrent events and terminal event data

In cardiovascular disease studies, a large number of risk factors are measured but it often remains unknown whether all of them are relevant variables and whether the impact of these variables is changing with time or remains constant. In addition, more than one kind of cardiovascular disease events can be observed in the same patient and events of different types are possibly correlated. It is expected that different kinds of events are associated with different covariates and the forms of covariate effects also vary between event types. To tackle these problems, we proposed a multistate modeling framework for the joint analysis of multitype recurrent events and terminal event. Model structure selection is performed to identify covariates with time-varying coefficients, time-independent coefficients, and null effects. This helps in understanding the disease process as it can detect relevant covariates and identify the temporal dynamics of the covariate effects. It also provides a more parsimonious model to achieve better risk prediction. The performance of the proposed model and selection method is evaluated in numerical studies and illustrated on a real dataset from the Atherosclerosis Risk in Communities study.     

Food factors and gastrointestinal function: a critical interface

The gastrointestinal tract (GIT) is an interface between the external environment and the body and functions to extract nutrients from foods as well as handle the various non-nutrient compounds found in foods. Thus factors in foods that affect health and disease may mediate their effects either through a direct effect on the GIT or indirectly by the pattern of absorption and subsequent metabolism through the GIT. To explore this relationship one must consider both the physiological responses of the GIT induced by factors in foods as well as the implications of GIT adaptation for metabolism. Metabolic adaptations to dietary factors such as cholesterol levels, glucose and insulin response, and immune function appear to be modulated by the manner in which food factors are metabolized in the GIT. New research is needed to understand the inter-relationship between food factors that stimulate GIT response and the subsequent influence on metabolism that influences risk factors for disease and health promotion.     

Telomere shortening in women resident close to waste landfill sites

Several studies demonstrate links between environmental stress and index of reduced health, including risk factors for cardiovascular disease, reduced immune function and cancer risks. We investigated the hypothesis that pollution, as an environmental stress, impacts health by modulating the rate of cellular aging in healthy pregnant women. Our research looked at the effects that illegal waste sites have on the localized population of pregnant women in Campania, Italy. As is often the case in illegal dumping, the effects on the population are often seen well before knowing what specific agents in the soil and water are responsible. Here we provide evidence that the pollution in this region is significantly associated with higher oxidative stress, shorter telomere length and lower telomerase activity, which are known determinants of cell senescence and aging-related meiotic dysfunction in women, in peripheral blood mononuclear cells from healthy pregnant women, subjected to therapeutic abortion in the second trimester of pregnancy. These findings may have implications for understanding how, at the cellular level, environmental stress may promote earlier onset of age-related diseases.     

Community nurse assessment of cardiovascular behavioural risk factors--a qualitative analysis within the CroHort study

The aim of our study was to identify major determinants of cardiovascular behavioural risk factors among subjects at increased risk of cardiovascular disease (CVD). The data for the qualitative analysis were obtained from the Croatian Adult Health Cohort Study (CroHort). The data analysis was based on the principles of Grounded Theory. We have generated the concept of an individual in a vicious circle of risky health behaviour, defined by the low level of motivation and unfavourable personal characteristics which in interaction with unsupportive social environment adversely influence one's health behaviour, leading to negative health outcomes that produce negative effects on one's motivation and social environment. Community nurses assessed that the respondents often weren't adequately recognising their CVD risk and were very reluctant about the change in their risky habits. Our results are supported by the quantitative analysis and are complementing other analyses of the cardiovascular risks within the CroHort study.