February 2016 - Page 2 of 2

Breast cancer—what part do behavioural factors play?

Posted on February 4, 2016November 23, 2022 by Priscille Rivière

Researchers at Unit 1018 “Centre for Research in Epidemiology and Population Health” (Inserm/Paris-Sud University) at Gustave Roussy have focused on the proportion of breast cancers attributable to various risk factors. The analysis, conducted among 67,634 women in the French E3N cohort, shows that postmenopausal breast cancers are more often attributable to “behavioural” factors, such as an unhealthy diet, excess weight and alcohol consumption than “non-behavioural” factors. These data suggest that by preventing these behaviour patterns, the number of breast cancers during menopause would decrease.
The article detailing these findings is published in the International Journal of Cancer, 04 February 2016.

Breast cancer is the most frequently diagnosed cancer among women worldwide. The number of “behavioural” risk factors, such as alcohol consumption and diet, and “non-behavioural” factors (family history, age at first menstruation and menopause, etc.) were already identified in the literature. Françoise Clavel-Chapelon, Research Director at Inserm and Laureen Dartois have focused on the proportion of breast cancer attributable to these factors and the combined impact of all of these risk factors, which has been poorly studied until now.

Researchers from the Inserm team “Generations and Health” at the Centre for Research in Epidemiology and Population Health (CESP, Inserm Unit 1018) have assessed the proportion of breast cancers diagnosed before and after menopause that are attributable to behavioural and non-behavioural risk factors. The study was conducted among 67,634 French women aged from 42 to 72 years old at inclusion in the French E3N cohort study.

Following 15 years of monitoring, 497 women were diagnosed with breast cancer before menopause and 3,138 after menopause.

“Premenopausal breast cancer is 61.2% attributable to non-behavioural factors and only 39.9% attributable to behavioural factors. Breast cancers diagnosed before menopause are not statistically attributable to any single behavioural factor.” explains Françoise Clavel-Chapelon, Inserm Research Director.

By contrast, the researcher clarifies that “over half (53.5%) of postmenopausal cancer cases could have been avoided by adapting behaviour.”

The main behavioural factors, which we can influence, that contribute to the onset of postmenopausal cancer are (percentage of avoidable cancers in brackets): use of hormone therapy for menopause (14.5%); an unbalanced diet (10.1%); alcohol consumption (more than one glass per day) (5.6%); excess weight in adulthood (BMI>=25kg/m2) (5.1%) and low weight during puberty (17.1%). It should be noted that hormone therapy for menopause is used much less in the last 10 years and that compositions have changed following the E3N results. Furthermore, excess weight during puberty is also included in these factors, although researchers are not able to fully explain the mechanism.

The authors conclude that “not engaging in these behaviour patterns may prevent over half of diagnosed postmenopausal breast cancers.”

They suggest continuing human and social science studies to understand individual behaviour choices, as well as developing and assessing interventions in order to modify them.

THE E3N (www.e3n.fr) AND E4N (www.e4n.fr) STUDIES

The E3N study, or Epidemiological Study of women in MGEN Mutuelle Générale de l’Education Nationale, a health insurance plan mainly covering teachers), headed by Françoise Clavel-Chapelon, Inserm Research Director, is a prospective cohort study of approximately 100,000 French female volunteers born between 1925 and 1950, and monitored since 1990.

Since 1990, women have completed and returned a self-administered questionnaire every 2-3 years. They are asked both about their lifestyle (diet, use of hormone treatments, etc.) and about changes in their state of health.

The E3N study is supported by four founding partners: Inserm, the French National Cancer League, Gustave Roussy Institute and MGEN.

The E4N study has just been launched, and is aimed at extending the E3N study by monitoring family members of E3N women. Ultimately, E4N will include three generations: E3N women and the fathers of their children constitute the first generation; their children, the second; and their grandchildren will form the third generation. Monitoring the three generations will make it possible to collect information on behavioural and environmental factors at different periods of life. The main objective of the E4N study is to study health in relation to environment and modern lifestyle in subjects from the same family with a shared genetic background and environment.

Alzheimer’s disease: a new immunotherapy approach?

Posted on February 2, 2016November 23, 2022 by Priscille Rivière

A study conducted on mice by researchers at Inserm and UPMC (Pierre and Marie Curie University) offers a new type of immunotherapy approach for treating Alzheimer’s disease. This involves amplifying a specific population of T lymphocytes that regulate immune and neuroinflammatory mechanisms that develop during the disease.
These results are published in the journal Brain.

A new immunotherapy strategy for treating Alzheimer’s disease. This may be validated by the new work carried out by the Inserm team “Immune System, Neuroinflammation and Neurodegenerative Diseases” at UMRS 938 “Saint-Antoine Research Centre” (Inserm/UPMC) in Paris. In recent years, a body of substantive work has enabled the start of gaining further insight into complex immune and neuroinflammatory mechanisms associated with Alzheimer’s disease. The Inserm team at the Saint-Antoine Research Centre offers further proof of concept on the efficacy of innovative immunotherapy strategy in mice that is based on an immunomodulation approach.

Researchers have shown, in earlier work with mice, that a specific population of T lymphocytes, known as T regulators (or Treg), modulated specific Ab peptide T lymphocytes that accumulate in the brains of sick people. “Treg cells may act in different ways to modulate T lymphocyte response in general. However, there are other aspects of neuroinflammatory reactions observed in this type of disease”, states Guillaume Dorothée, Inserm Research Fellow in charge of this study. As such, researchers chose to evaluate the effect of Treg cells on disease progression using a mouse model.

Interleukin-2: Therapeutic Strategy

To do this, they either depleted or amplified Treg cells at the early stage of the disease. They found that a Treg deficiency accelerated the onset of cognitive disorders and was associated with a decrease in the presence of microglial cells in deposits of Ab peptide.

“Additional studies seem to suggest a change in the functional profile of these inflammatory cells that are chronically activated during the disease which would have a rather beneficial role early in the disease process”, according to the researcher.

By contrast, prolonged Treg amplification using low doses of interleukin-2 injected intraperitoneally increases the microglial cell response and delays the onset of memory impairment.

This immunomodulation approach involving the injection of low doses of interleukin-2, already tested in some bone marrow transplant clinical protocols and for type 1 diabetes, now seems to be a new therapeutic strategy for Alzheimer’s disease. Researchers are already planning a pilot clinical trial in humans and are also considering the possibility of modulating some specific sub-populations of T lymphocytes to refine the response.

Listeria: hypervirulent strains with cerebral and placental tropism

Posted on February 1, 2016November 23, 2022 by Priscille Rivière

Researchers from the Institut Pasteur, Inserm, CNRS and Paris Descartes – Sorbonne Paris Cité University recently published a large-scale study in Nature Genetics based on almost 7,000 strains of Listeria monocytogenes — the bacterium responsible for human listeriosis, a severe foodborne infection. Through the integrative analysis of epidemiological, clinical and microbiological data, the researchers have revealed the highly diverse pathogenicity of isolates belonging to this bacterial species.
Comparative genomics led them to discover new virulence factors, which were demonstrated experimentally as involved in cerebral and fetal-placental listeriosis. In addition, this research points to the importance of using new reference strains, which are representative of the hypervirulent lineages identified here, for experimental research on Listeria monocytogenes pathogenesis.

In France, as in many other countries, the Listeria monocytogenes bacterium — which is responsible for listeriosis, a severe foodborne infection, especially in pregnant women and the elderly — is subjected to a stringent microbiological monitoring system, coordinated at the Institut Pasteur by the National Reference Center (CNR) for Listeria together with the French Institute for Public Health Surveillance (InVS). Researchers from the Biology of Infection Unit (Institut Pasteur/Inserm), headed by Marc Lecuit (Paris Descartes – Sorbonne Paris Cité University, Necker-Enfants Malades Hospital, AP-HP) and home to the Listeria CNR, together with the group led by Sylvain Brisse in the Microbial Evolutionary Genomics Unit (Institut Pasteur/CNRS), recently published the findings of a broad study of close to 7,000 strains of Listeria monocytogenes isolates collected over the past nine years for monitoring purposes.

First and foremost, bacterial molecular genotyping revealed considerable heterogeneity within the L. monocytogenes species, and showed that strains can be categorized into distinct genetic families (or clonal groups). By analyzing epidemiological data, the researchers showed that some of these clonal groups are more frequently associated with human infections, while others are closely linked to food. The comprehensive analysis of detailed clinical data from over 800 patients with listeriosis showed that the strains most often associated with infections are more frequently isolated in the least immunodeficient patients while the strains most commonly linked to food mainly infect the most immunodeficient individuals. In addition, the strains most often involved in infections appear to be the most invasive as they infect the central nervous system and fetus more often than the strains most commonly associated with food. These findings suggested the existence of hypervirulent strains — an hypothesis that scientists confirmed thanks to a humanized mouse model of listeriosis they developed previously[1].

To uncover the genetic basis of this hypervirulence, the researchers sequenced the genomes of around a hundred strains that are representative of the most prevalent clonal groups. Comparative analysis of these genome sequences identified a large number of genes closely linked to the hypervirulent clonal groups, including one which was demonstrated as involved in the cerebral and fetal-placental tropism of L. monocytogenes experimentally.

These results pave the way to a detailed understanding of the mechanisms underlying L. monocytogenes central nervous system and fetal-placental invasion.

While current research on L. monocytogenes is conducted with so called “reference” strains, which are not hypervirulent, this research supports the use of hypervirulent strains representative of human infections, to ensure the clinical and pathophysiological relevance of experimental research.

This study illustrates the exceptional power of harnessing the biodiversity of a given microbial species (here L. monocytogenes) and integrating epidemiological, clinical, bacteriological and experimental data to study the biology of infection in a clinically relevant manner.

[1] See the press release (September 17, 2008)

Inserm Newsroom - Press room of the French national institute of health and medical research

Month: February 2016

Breast cancer—what part do behavioural factors play?

The authors conclude that “not engaging in these behaviour patterns may prevent over half of diagnosed postmenopausal breast cancers.”

Alzheimer’s disease: a new immunotherapy approach?

“Additional studies seem to suggest a change in the functional profile of these inflammatory cells that are chronically activated during the disease which would have a rather beneficial role early in the disease process”, according to the researcher.

Listeria: hypervirulent strains with cerebral and placental tropism

These results pave the way to a detailed understanding of the mechanisms underlying L. monocytogenes central nervous system and fetal-placental invasion.