Review articleRelationship between exposure to mixtures of persistent, bioaccumulative, and toxic chemicals and cancer risk: A systematic review
Introduction
Human health depends on factors related both to individual circumstances and to the environment [World Health Organization (WHO) 2010]. Exposure to environmental risks has increased exponentially since the industrial revolution in the 19th century, and especially in recent decades with the transformation of modern society. Some of these environmental factors are harmful to human health, collaborating in the occurrence of infections and many chronic diseases (Muralikrishna and Manickam, 2017). Globally, it is estimated that environmental factors are responsible for 23% of deaths worldwide and for 22% of the total disease burden in terms of disability-adjusted life years (DALYs) (Vineis and Fecht, 2018).
Among environmental pollutants, an important group known as persistent, bioaccumulative, and toxic (PBT) chemicals is of special concern because they combine three undesired features. They are resistant to degradation and persistent in the environment for long periods of time, tend to bioaccumulate both in human and other organisms tissues, and are toxic (Matthies et al., 2016). They include heavy metals, organochlorines or organochlorine compounds (OCCs), polychlorinated biphenyls (PCBs), organobromines including brominated flame retardants (BFRs), organofluorines, and polycyclic aromatic hydrocarbons (PAHs) among others. Although there is a wide range of these substances, the most prevalent are organochlorines, which were extensively used as pesticides, and compounds with industrial uses, such as PCBs and organobrominated biphenyls (Ritter et al., 1995).
In the classical study of toxicity from environmental compounds, researchers sought to measure exposure levels and to define reference values at which health risks were foreseeable. Regrettably, from the empirical evidence obtained it cannot be affirmed that levels of contamination within the reference values are safe, since no observed adverse effects at a given level of contamination do not mean zero risk (Goodson et al., 2015). However, the measurement challenge is not limited to the problem of determining safe values. As environmental exposures usually simultaneously involve a multitude of pollutants, even low dose exposure to individual substances may have serious long-term health effects given their additive potential (Kortenkamp et al., 2007) and the possibility of synergic effects. For instance, many PBTs are endocrine disruptors, i.e. chemicals compounds that interfere with different axes of the endocrine system mimicking or antagonizing hormones or their receptors (Dickerson and Gore, 2007). Accordingly, the evaluation of their effect on health should consider and analyze this joint exposure. Further support comes from the European Food Safety Authority (EFSA), which identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area, and so, recently published a guidance on assessment of combined effects of chemical mixtures. In this line, some EFSA panels and units have initiated activities to study such combined exposures, expanding on the approaches for single chemical risk assessments (EFSA Scientific Committee et al., 2019).
Unfortunately, most studies conducted in this field have not taken this approach, preferring, instead, to focus on the effects of each contaminant alone. If we define a mixture as the combination of several environmental pollutants, which may be from the same family (e.g. different PCBs) or a combination, very few studies of mixtures have been performed that analyze their combined effect on health, and specifically in cancer, and among them, the majority have examined the relationship between PBTs and the risk of breast cancer (Boada et al., 2012; Ibarluzea et al., 2004; Pastor-Barriuso et al., 2016).
In terms of pollution's deleterious effects on human health, one of the most severe is cancer, which is the second leading cause of death worldwide (second only to cardiovascular disease) provoking almost ten million deaths annually (GBD 2017 Causes of Death Collaborators, 2018). It is estimated that 16% of cancer deaths are attributable to environmental risk factors (of which 36% correspond to lung cancer) (Vineis and Fecht, 2018).
The aim of this study is to compile and analyze evidence on the relationship between exposure to mixtures of persistent pollutants and the risk of developing cancer in the general population.
Section snippets
Methods
A systematic review was conducted following a pre-established protocol and according to the general methodology of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline (Moher et al., 2009).
Search results
The database search yielded 2379 results, 22 additional records were added from secondary data sources producing a total of 2401 possible studies which, after eliminating duplicates, were reduced to 2319. Title and abstract screening resulted in 43 articles selected for full text reading. Twenty-one of them did not meet the inclusion/exclusion criteria. Thus, 22 articles were included in the final full review, of which seven corresponded to cross-references (Fig. 1).
Description of studies
The general features of the
Mixtures of PBTs and the risk of cancer
This review presents and summarizes recently published evidence on the relationship between exposure to mixtures of PBTs and the risk of developing cancer. The results obtained in the studies evaluated indicate that mixtures of PBTs are associated with an increased risk of developing certain types of cancer. However, these results vary widely, depending on the family of mixtures and on the population exposed to them.
CRediT authorship contribution statement
Nicolás Francisco Fernández-Martínez: Methodology, Formal analysis, Investigation, Writing - original draft, Visualization. Ana Ching-López: Investigation, Writing - original draft, Visualization, Writing - review & editing. Antonio Olry de Labry Lima: Validation, Writing - review & editing. Elena Salamanca-Fernández: Validation, Writing - review & editing. Beatriz Pérez-Gómez: Writing - review & editing. José Juan Jiménez-Moleón: Writing - review & editing. Maria José Sánchez:
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by the Regional Ministry of Health, Andalusian Government, Spain [grant number PS-0281-2016].
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