Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the ‘normal’ epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution may cause lung cancer. Despite the prospective nature and consistent findings of these studies, causality assessment can benefit from biomarker research. In the present systematic review, we assess the contribution of intermediate biomarkers in epidemiological studies, to ascertain whether their measurement reinforces causal reasoning. We have reviewed 524 papers which described the relationships between ambient air pollution and biological markers of dose and early response. The evidence for each marker was evaluated using assessment criteria which rate a group of studies from A (strong) to C (weak) on amount of evidence, replication of findings, and protection from bias. Biomarkers that scored A or B for all three criteria are included here. The markers that fulfilled the inclusion criteria are: 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, oxidative damage to nucleobases, and methylation changes. These biomarkers cover the whole spectrum of disease onset and progression from external exposure to tumour formation and some have also been suggested as risk predictors of future cancer, reinforcing causal reasoning. However, methodological issues such as confounding, publication bias and use of surrogate tissues instead of target tissues in studies on these markers are of concern. The identified biological markers have potential to shed light on the pathways of carcinogenesis, thus defining the association more clearly for public health interventions.

Background: Following wider acceptance of ‘the thrifty phenotype’ hypothesis and the convincing evidence that early‐life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early‐life exposures become biologically embedded.Materials and methods: In this review, we summarize the current literature regarding biological embedding of early‐life experiences. To this end, we conducted a literature search to identify studies investigating early‐life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta‐analyses were not feasible given the nature of the evidence.Results: We identified seven studies on early‐life socio‐economic circumstances, 10 studies on childhood obesity and six studies on early‐life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias and causality are concerns remaining to be addressed in future investigations.Conclusions: Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early‐life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early‐life exposures might become biologically embedded through epigenetic effects.

Diet has long been suspected to impact on breast cancer risk. In this study we evaluated whether the degree of adherence to a Mediterranean diet pattern modifies breast cancer risk amongst Greek-Cypriot women. Subjects included 935 cases and 817 controls, all participating in the MASTOS case-control study in Cyprus. The study was approved by the Cyprus National Bioethics Committee. Information on dietary intakes was collected using an interviewer administered 32-item Food Frequency Questionnaire. Information on demographic, anthropometric, lifestyle, and other confounding factors was also collected. Adherence to the Mediterranean Diet pattern was assessed using two a-priory defined diet scores. In addition, dietary patterns specific to our population were derived using Principal Component Analysis (PCA). Logistic regression models were used to assess the association between the dietary patters and breast cancer risk. There was no association with breast cancer risk for either score, however, higher consumptions of vegetables, fish and olive oil, were independently associated with decreased risk. In addition, the PCA derived component which included vegetables, fruit, fish and legumes was shown to significantly reduce risk of breast cancer (ORs across quartiles of increasing levels of consumption: 0.89 95%CI: 0.65-1.22, 0.64 95%CI: 0.47-0.88, 0.67 95%CI: 0.49-0.92, P trend < 0.0001), even after adjustment for relevant confounders. Our results suggest that adherence to a diet pattern rich in vegetables, fish, legumes and olive oil may favorably influence the risk of breast cancer. This study is the first investigation of dietary effects on breast cancer risk in Cyprus, a country whose population has traditionally adhered to the Mediterranean diet.

Background: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. Methods: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015–2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015–2019 average and (ii) difference between observed and expected 2020 deaths. Results: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. Conclusions: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.