Number of lifetime menses increases breast cancer occurrence in postmenopausal women at high familial risk

Authors: Margaux Bieuville, Dominique Faugère, Virginie Galibert, Morgane Henard, Antoine M. Dujon, Beata Ujvari, Pascal Pujol, Benjamin Roche and Frédéric Thomas

Source: Frontiers in Ecology and Evolution (Feb 2023)

Abstract

It is increasingly thought that part of human susceptibility to cancer is the result of evolutionary mismatches: our ancestors evolved cancer suppression mechanisms in a world largely different from our modern environments. In that context, it has been shown in cohorts from general Western populations that reproductive traits modulate breast cancer risk.

Overall, the more menses women experience, the more at risk they are to develop postmenopausal breast cancer. This points towards an evolutionary mismatch but brings the question whether the reproductive pattern also modulates the breast cancer risk in menopausal women at high familial risk.

We thus studied the influence of menses on breast cancer risk in a case–control study of 90 postmenopausal women (including BRCA1/2 and non BRCA1/2) nested within a cohort at high familial risk. We tested the association of the lifetime number of menses and the number of menses before first full-term pregnancy with postmenopausal breast cancer risk using Cox survival models.

We showed that the total lifetime number of menses was significantly associated with postmenopausal breast cancer risk and associated with a quicker onset of breast cancer after menopause. Those results align with similar studies lead in general cohorts and suggest that the reproductive pattern modulates the familial risk of developing breast cancer after menopause.

Altogether, those results impact how we envision breast cancer prevention and call for more research on how ecological and genetic factors shape breast cancer risk.

The impact of an extreme climatic event on adder (Vipera berus) demography in southern Sweden

Authors: Thomas Madsen, Jon Loman, Dirk Bauwens, Bo Stille, Håkan Anderberg, Lewis Anderberg, Beata Ujvari

Source: Biological Journal of the Linnean Society (Feb 2023)

Abstract

Climate change has been shown to have significant negative effects on wildlife populations owing to both gradual shifts in mean climatic conditions and an increased frequency of extreme climatic events. Based on a long-term study spanning 40 years, we explore the demographic effect of the exceptionally hot and dry summer of 2018 on the demography of an isolated adder (Vipera berus) population in southern Sweden.

In spring 2019, we observed a dramatic decline in adder relative body mass and a concomitant 50% reduction in population size. Our results strongly suggest that the negative impacts on adder demography were the result of a combination of low prey abundance and adder dehydration caused by the extreme climatic conditions during the previous summer.

The study provides an example of the significant negative effects of ongoing climate change on vertebrate populations and emphasizes the importance of long-term studies to document the demographic effects of extreme climatic events.

No evidence that spice consumption is a cancer prevention mechanism in human populations

Authors: Antoine M Dujon, Aurélie Tasiemski, Pascal Pujol, Anthony Turpin, Beata Ujvari, Frédéric Thomas

Source: Evolution, Medicine, and Public Health (Nov 2022)

Abstract

Why humans historically began to incorporate spices into their diets is still a matter of unresolved debate. For example, a recent study (Bromham et al. 2021, Nat Hum Behav) did not support the most popular hypothesis that spice consumption was a practice favoured by selection in certain environments to reduce food poisoning, parasitic infections, and foodborne diseases.

Because several spices are known to have anticancer effects, we explored, using the same dataset, the hypothesis that natural selection and/or cultural evolution may have favoured spice consumption as an adaptive prophylactic response to reduce the burden of cancerous pathologies.

Patterns of spice use in 36 countries, however, are not consistent with a cancer mitigation mechanism: the age-standardised rate of almost all gastrointestinal cancers was not related to spice consumption. Thus, directions other than foodborne pathogens and cancers should be explored to understand the health reasons, if any, why our ancestors developed a taste for spices.

Polyandry and non-random fertilisation maintain long-term genetic diversity in an isolated island population of adders (Vipera berus)

Authors: Thomas Madsen, Beata Ujvari, Dirk Bauwens, Bernd Gruber, Arthur Georges & Marcel Klaassen

Source: Heredity (Dec 2022)

Abstract

Conservation genetic theory suggests that small and isolated populations should be subject to reduced genetic diversity i.e., heterozygosity and allelic diversity. Our 34 years study of an isolated island population of adders (Vipera berus) in southern Sweden challenges this notion.

Despite a lack of gene flow and a yearly mean estimated reproductive adult population size of only 65 adult adders (range 12–171), the population maintains high levels of heterozygosity and allelic diversity similar to that observed in two mainland populations. Even a 14-year major “bottleneck” i.e., a reduction in adult adder numbers, encompassing at least four adder generations, did not result in any reduction in the island adders’ heterozygosity and allelic diversity. Female adders are polyandrous, and fertilisation is non-random, which our empirical data and modelling suggest are underpinning the maintenance of the population’s high level of heterozygosity.

Our empirical results and subsequent modelling suggest that the positive genetic effects of polyandry in combination with non-random fertilisation, often overlooked in conservation genetic analyses, deserve greater consideration when predicting long-term survival of small and isolated populations.

Transmissible cancer and longitudinal telomere dynamics in Tasmanian devils (Sarcophilus harrisii)

Authors: Thomas Madsen, Marcel Klaassen, Nynke Raven, Antoine M. Dujon, Geordie Jennings, Frédéric Thomas, Rodrigo Hamede, Beata Ujvari

Source: Molecular Ecology (Oct 2022)

Abstract

A plethora of intrinsic and environmental factors have been shown to influence the length of telomeres, the protector of chromosome ends. Despite the growing interest in infection–telomere interactions, there is very limited knowledge on how transmissible cancers influence telomere maintenance. An emblematic example of transmissible cancer occurs in the Tasmanian devil (Sarcophilus harrisii), whose populations have been dramatically reduced by infectious cancer cells.

To investigate associations between telomere dynamics and the transmissible cancer, we used longitudinal data from a Tasmanian devil population that has been exposed to the disease for over 15 years. We detected substantial temporal variation in individual telomere length (TL), and a positive significant association between TL and age, as well as a marginally significant trend for devils with devil facial tumour disease (DFTD) having longer telomeres. A proportional hazard analysis yielded no significant effect of TL on the development of DFTD.

Like previous studies, we show the complexity that TL dynamics may exhibit across the lifetime of organisms. Our work highlights the importance of long-term longitudinal sampling for understanding the effects of wildlife diseases on TL.

Tumors alter life history traits in the freshwater cnidarian, Hydra oligactis

Authors: Justine Boutry, Sophie Tissot, Narimène Mekaoui, Antoine M. Dujon, Jordan Meliani, Rodrigo Hamede, Beata Ujvari, Aurora M. Nedelcu, Jácint Tokolyi, Frédéric Thomas

Source: iScience (Aug 2022)

Abstract

Although tumors can occur during the lifetime of most multicellular organisms and have the potential to influence health, how they alter life-history traits in tumor-bearing individuals remains poorly documented. This question was explored using the freshwater cnidarian Hydra oligactis, a species sometimes affected by vertically transmitted tumors.

We found that tumorous polyps have a reduced survival compared to healthy ones. However, they also displayed higher asexual reproductive effort, by producing more often multiple buds than healthy ones. A similar acceleration is observed for the sexual reproduction (estimated through gamete production). Because tumoral cells are not transmitted through this reproductive mode, this finding suggests that hosts may adaptively respond to tumors, compensating the expected fitness losses by increasing their immediate reproductive effort.

This study supports the hypothesis that tumorigenesis has the potential to influence the biology, ecology, and evolution of multicellular species, and thus should be considered more by evolutionary ecologists.

Nocturnal circulating tumor cells: The ultimate selective filter in cancer progression?

Authors: Frédéric Thomas, Antoine M. Dujon, Beáta Újvári, Catherine Alix-Panabières

Source: Med (Aug 2022)

Abstract

The survival duration of circulating tumor cells (CTCs) in the vasculature is a critical parameter in the establishment of the metastatic cascade.

Diamantopoulou and colleagues demonstrate that the metastatic capacity of CTCs is strongly influenced by circadian rhythms, suggesting a rationale for the time-controlled interrogation and treatment of metastatic cancers.

Small extracellular vesicle DNA-mediated horizontal gene transfer as a driving force for tumor evolution: Facts and riddles

Authors: Gábor Valcz, Beáta Újvári, Edit I. Buzás, et al.

Source: FRONTIERS IN ONCOLOGY (Aug 2022)

Abstract

The basis of the conventional gene-centric view on tumor evolution is that vertically inherited mutations largely define the properties of tumor cells. In recent years, however, accumulating evidence shows that both the tumor cells and their microenvironment may acquire external, non-vertically inherited genetic properties via horizontal gene transfer (HGT), particularly through small extracellular vesicles (sEVs).

Many phases of sEV-mediated HGT have been described, such as DNA packaging into small vesicles, their release, uptake by recipient cells, and incorporation of sEV-DNA into the recipient genome to modify the phenotype and properties of cells. Recent techniques in sEV separation, genome sequencing and editing, as well as the identification of new secretion mechanisms, shed light on a number of additional details of this phenomenon.

Here, we discuss the key features of this form of gene transfer and make an attempt to draw relevant conclusions on the contribution of HGT to tumor evolution.

A review of the methods used to induce cancer in invertebrates to study its effects on the evolution of species and ecosystem functioning

Authors: Antoine M. Dujon, Justine Boutry, Sophie Tissot, Jordan Meliani, Lena Guimard, Océane Rieu, Beata Ujvari, Frédéric Thomas

Source: Methods in Ecology and Evolution (Jul 2022)

Abstract

Cancer is an understudied but important process in wildlife that is predicted to have a significant effect on the evolution of metazoan species due to negative effects on host fitness. However, gaining understanding of the impact of cancer on species and ecosystems is currently relatively slow as the development of both animal models in which cancer can be induced and experiments that can be performed in an ecological setting are required. Invertebrates, because they are widely available and relatively easy to manipulate, are promising animal models.

In this review we examine how tumours can be induced in invertebrates to use them as experimental models to study the effects of cancer on the ecology and evolution of species. We identified four main groups of invertebrates (planarian, bivalves, hydra and drosophila) in which such inductions are performed. We then reviewed the types and effectiveness of the methods employed to induce tumours in those groups.

Cancer alters the phenotype of the host. We review how experiments using invertebrate models can be used to investigate the impact of cancer on tumour-bearing individuals for their movement, reproduction, feeding behaviours, social interactions, holobiont and predation risk.

We provide recommendations to facilitate the development of new invertebrate models. We also highlight a series of key questions on the ecology and evolution of cancer that could be answered with the use of invertebrate models.

Transmissible Cancer Evolution: The Under-Estimated Role of Environmental Factors in the “Perfect Storm” Theory

Authors: Sophie Tissot, Anne-Lise Gérard, Justine Boutry, Antoine M. Dujon, Tracey Russel, Hannah Siddle, Aurélie Tasiemski, Jordan Meliani, Rodrigo Hamede, Benjamin Roche, Beata Ujvari and Frédéric Thomas

Source: Pathogens (Feb 2022)

Abstract

Although the true prevalence of transmissible cancers is not known, these atypical malignancies are likely rare in the wild. The reasons behind this rarity are only partially understood, but the “Perfect Storm hypothesis” suggests that transmissible cancers are infrequent because a precise confluence of tumor and host traits is required for their emergence.

This explanation is plausible as transmissible cancers, like all emerging pathogens, will need specific biotic and abiotic conditions to be able to not only emerge, but to spread to detectable levels. Because those conditions would be rarely met, transmissible cancers would rarely spread, and thus most of the time disappear, even though they would regularly appear. Thus, further research is needed to identify the most important factors that can facilitate or block the emergence of transmissible cancers and influence their evolution.

Such investigations are particularly relevant given that human activities are increasingly encroaching into wild areas, altering ecosystems and their processes, which can influence the conditions needed for the emergence and spread of transmissible cell lines.