Elsevier

Environmental Research

Volume 188, September 2020, 109787
Environmental Research

Review article
Relationship between exposure to mixtures of persistent, bioaccumulative, and toxic chemicals and cancer risk: A systematic review

https://doi.org/10.1016/j.envres.2020.109787Get rights and content

Abstract

Environmental risks are responsible for one in five of all deaths worldwide. Persistent, bioaccumulative, and toxic substances are chemicals that can subsist for decades in human tissues and the environment. They include heavy metals, organochlorines, polychlorinated biphenyls, organobromines, organofluorines, and polycyclic aromatic hydrocarbons among others. Although humans are often exposed to multiple pollutants simultaneously, their negative effects on health have generally been studied for each one separately. Among the most severe of these harmful effects is cancer.

Here, to compile and analyze the available evidence on the relationship between exposure to mixtures of persistent, bioaccumulative, and toxic chemicals and the risk of developing cancer in the general population, we provide a systematic review based on the main databases (Cochrane, PubMed and Embase), together with complementary sources, using the general methodology of the PRISMA Statement. The articles analyzed were selected by two researchers working independently and their quality was evaluated by reference to the Newcastle-Ottawa scale.

The initial search yielded 2379 results from the main sources of information and 22 from the complementary ones. After the article selection process, 22 were included in the final review (21 case-control studies and one cohort study). Analysis of the selected studies revealed that most of the mixtures analyzed were positively associated with risk of cancer, especially that of the breast, colon-rectum or testis, and more strongly so than each contaminant alone.

In view of the possible stronger association observed with the development of cancer for some mixtures of pollutants than when each one is present separately, exposure to mixtures should also be monitored and measured, preferably in cohort designs, to complement the traditional approach to persistent, bioaccumulative, and toxic chemicals. The results presented should be taken into account in public health policies in order to strengthen the regulatory framework for cancer prevention and control.

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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