Diet, genetic susceptibility and carcinogenesis

AbstractAt 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 darwinian perspective: right premises, questionable conclusion. A commentary on Niall Shanks and Rebecca Pyles' "Evolution and medicine: the long reach of "Dr. Darwin""

As Dobzhansky wrote, nothing in biology makes sense outside the context of the evolutionary theory, and this truth has not been sufficiently explored yet by medicine. We comment on Shanks and Pyles' recently published paper, Evolution and medicine: the long reach of "Dr. Darwin", and discuss some recent advancements in the application of evolutionary theory to carcinogenesis. However, we disagree with Shanks and Pyles about the usefulness of animal experiments in predicting human hazards. Based on the darwinian observation of inter-species and inter-individual variation in all biological functions, Shanks and Pyles suggest that animal experiments cannot be used to identify hazards to human health. We claim that while the activity of enzymes may vary among individuals and among species, this does not indicate that critical events in disease processes occurring after exposure to hazardous agents differ qualitatively between animal models and humans. In addition, the goal is to avoid human disease whenever possible and with the means that are available at a given point in time. Epidemics of cancer could have been prevented if experimental data had been used to reduce human exposures or ban carcinogenic chemicals. We discuss examples

Causal models in epidemiology: past inheritance and genetic future

The eruption of genetic research presents a tremendous opportunity to epidemiologists to improve our ability to identify causes of ill health. Epidemiologists have enthusiastically embraced the new tools of genomics and proteomics to investigate gene-environment interactions. We argue that neither the full import nor limitations of such studies can be appreciated without clarifying underlying theoretical models of interaction, etiologic fraction, and the fundamental concept of causality. We therefore explore different models of causality in the epidemiology of disease arising out of genes, environments, and the interplay between environments and genes. We begin from Rothman's "pie" model of necessary and sufficient causes, and then discuss newer approaches, which provide additional insights into multifactorial causal processes. These include directed acyclic graphs and structural equation models. Caution is urged in the application of two essential and closely related concepts found in many studies: interaction (effect modification) and the etiologic or attributable fraction. We review these concepts and present four important limitations. 1. Interaction is a fundamental characteristic of any causal process involving a series of probabilistic steps, and not a second-order phenomenon identified after first accounting for "main effects". 2. Standard methods of assessing interaction do not adequately consider the life course, and the temporal dynamics through which an individual's sufficient cause is completed. Different individuals may be at different stages of development along the path to disease, but this is not usually measurable. Thus, for example, acquired susceptibility in children can be an important source of variation. 3. A distinction must be made between individual-based and population-level models. Most epidemiologic discussions of causality fail to make this distinction. 4. At the population level, there is additional uncertainty in quantifying interaction and assigning etiologic fractions to different necessary causes because of ignorance about the components of the sufficient cause

Climate change impacts on water salinity and health

AbstractIt is estimated that 884 million people do not have access to clean drinking water in the world. Increasing salinity of natural drinking water sources has been reported as one of the many problems that affect low-income countries, but one which has not been fully explored. This problem is exacerbated by rising sea-levels, owing to climate change, and other contributing factors, like changes in fresh water flow from rivers and increased shrimp farming along the coastal areas. In some countries, desalination plants are used to partly remove salt and other minerals from water sources, but this is unlikely to be a sustainable option for low-income countries affected by high salinity. Using the example of Bangladesh as a model country, the following research indicates that the problem of salinity can have serious implications with regard to rising rates of hypertension and other public health problems among large sectors of the worldwide population

Ability to pay and equity in access to Italian and British National Health Services

Background: Equity in delivery and distribution of health care is an important determinant of health and a cornerstone in the long way to social justice. We performed a comparative analysis of the prevalence of Italian and British residents who have fully paid out-of-pocket for health services which they could have obtained free of charge or at a lower cost from their respective National Health Services. Methods: Cross-sectional study based on a standardized questionnaire survey carried out in autumn 2006 among two representative samples (n = 1000) of the general population aged 20-74 years in each of the two countries. Results: 78% (OR 19.9; 95% CI 15.5-25.6) of Italian residents have fully paid out-of-pocket for at least one access to health services in their lives, and 45% (OR 18.1; 95% CI 12.9-25.5) for more than five accesses. Considering only the last 2 years, 61% (OR 16.5; 95% CI 12.6-21.5) of Italians have fully paid out-of-pocket for at least one access. The corresponding pattern for British residents is 20 and 4% for lifelong prevalence, and 10% for the last 2 years. Conclusions: Opening the public health facilities to a privileged private access to all hospital physicians based on patient's ability to pay, as Italy does, could be a source of social inequality in access to care and could probably represent a major obstacle to decreasing waiting times for patients in the standard formal ‘free of charge' way of acces

COVID-19 as a Syndemic.

A Perspective on 'A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19' by Logette E, Lorin C, Favreau C, Oshurko E, Coggan JS, Casalegno F, Sy MF, Monney C, Bertschy M, Delattre E, Fonta P-A, Krepl J, Schmidt S, Keller D, Kerrien S, Scantamburlo E, Kaufmann A-K and Markram H (2021). Front. Public Health. 2:27. doi: 10.3389/fpubh.2021.69513