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Identification of metabolic signatures related to stress and breast cancer risk and survival

This study examines the associations between self-reported stress and breast cancer risk and survival, and then identify novel blood markers of stress.

Researcher: Dr Yahya Mahamat-Saleh
Grant type: INSPIRE Research Challenge
Countries: France
Cancer types: Breast
Exposures: Stress
Status: Ongoing
Area: Cancer prevention

This project, which uses large-scale metabolomics data, represents a unique opportunity to identify novel biomarkers of stress that can enhance our understanding of the underlying biological mechanisms linking stress to breast cancer risk and survival in black African women. The findings arising from this project may have public health implications in terms of primary and tertiary prevention of breast cancer
Dr Yahya Mahamat-Saleh

Background

Millions of women around the world are diagnosed with breast cancer (BC) every year, making it the most common type of cancer. In the coming decades, the number of women diagnosed with BC in Sub-Saharan Africa is projected to double, due to population aging and growth as well as societal changes, including the adoption of western lifestyles. Several factors are known to increase the risk of BC, for example drinking too much alcohol, having too much body fat, not doing enough exercise, and various hormonal and reproductive factors; but these modifiable risk factors can partially explain the increasing number of women with BC. Previous studies suggested that stressful life events may influence the risk of BC and survival rates. However, our understanding of the complex relationship between stress and BC risk and survival is still limited. In particular, the biological mechanisms by which stress may influence BC risk or prognosis are not well understood. Metabolomics can measure hundreds to thousands of small molecules, known as metabolites, present in human blood. Some of these metabolites are likely to be influenced by stress, and we recently observed that women with high levels of cortisol —a stress-related metabolite—had a higher risk of BC. Although combinations of metabolites can be successfully used in epidemiological studies, no previous studies have identified blood metabolite markers that were associated with both stress and BC risk or survival.

In order to reduce the number of women getting BC and improve BC survival rates, we need to understand how stress can lead to BC development and influence survival by identifying novel biomarkers of stress that can enhance our understanding of the biological mechanisms linking stress to BC risk and survival.

Aims and objectives

This study aims to examine the associations between self-reported stress and breast cancer (BC) risk and survival, and then identify novel blood markers of stress. Subsequently, we will assess the relationship between these stress-related markers and BC risk and survival. Lastly, we will explore whether this blood marker of stress mediates the association between stress and BC risk and survival.

How it will be done

We will use data from women who participated in the previous South African Breast Cancer study in Soweto. Women completed questionnaires detailing lifestyle and environmental factors, including stress exposure, and they also provided blood samples. Thousands of small molecules have been measured from their blood samples. Women who developed BC were followed over time and clinical information was collected. Using appropriate statistical tools, we will construct blood markers of stress, and then explore whether this novel marker improves our ability to predict which women have the highest risk or those who have a poor prognosis.

Potential impact

The innovative aspect of this project is the identification of novel markers of stress in blood that enhances our understanding of the complex association between stress and BC risk and survival, and of the underlying biological mechanisms. Our results will help to develop new strategies to prevent BC and improve the prognosis of women with BC.