By bringing together the complementary expertise of three teams, this project will help shed light on the role of cholesterol metabolism in breast cancer development, a research question that has been debated for many years.
Dr Laure Dossus
Background
Managing cholesterol is essential for overall and cardiovascular health but its role in cancer prevention is still debated. Maintaining a healthy body weight, being physically active and having a healthy diet with low consumption of alcohol and saturated fat but rich in fibres can lower blood cholesterol.
Breast cancer remains a public health concern and researchers have long speculated about the role of cholesterol metabolism in its development. One study among German women, showed that those with elevated blood levels of the most abundant cholesterol metabolite in blood, 27-hydroxycholesterol (27HC), had less risk to develop breast cancer. This was confirmed by another study in a multiethnic population.
Aims and objectives
Thus, we propose to investigate in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (a large European cohort of half a million men and women), the relationship between cholesterol metabolites and breast cancer risk, specifically focusing on 27HC and compounds recently discovered by researchers involved in this project: oncosterone (OCDO), dendrogenin A (DDA) and their 27-hydroxylated forms. These compounds have shown opposite effects on breast tumours, making their exploration essential.
More specifically, in this project we will:
1- Measure cholesterol metabolites in women from EPIC (cancer-free and diagnosed with breast cancer), evaluate their association with the risk of developing breast cancer overall and whether this association vary depending on breast cancer characteristics (i.e. hormone-dependent cancers)
2 – Evaluate, in the EPIC cohort, the associations between cholesterol metabolites and lifestyle and dietary factors
3 – Assess the proportion of the association between nutritional and dietary factors and postmenopausal breast cancer that can be explained by cholesterol metabolites (e.g. to what extend the increase in postmenopausal breast cancer risk observed with obesity could be explained by increased levels of some cholesterol metabolites in obese women).
How it will be done
The study will involve around 2,000 women from the EPIC cohort: 1,000 women that have been diagnosed with breast cancer and 1000 cancer-free women with similar characteristics. Cholesterol metabolites will be measure in blood samples from participants, collected before cancer diagnosis. Additionally, because sex hormones share biological pathways with cholesterol, we will measure them on the same population.
We will compare blood cholesterol metabolites from breast cancer cases and cancer-free women and evaluate if women with higher blood levels of these metabolites are at higher or lower risk of developing breast cancer. We will also investigate how these cholesterol metabolites relate to obesity and lifestyle choices, like diet (such as Western or healthy diets, consumption of processed or ultra-processed food, plant-based diets or consumption of alcohol), as well as physical activity. In addition, we will evaluate to what extend the associations with postmenopausal breast cancer risk observed for these lifestyle factors could be explained by changes in blood levels of some cholesterol metabolites.
Potential impact
Our project unites the knowledge and skills of three research teams, with a common goal of understanding cholesterol’s role in the development of breast cancer, a question that has puzzled researchers for many years.