Risk of breast cancer in persons born after assisted reproductive technologies (ART)

Summary

Studies suggest an increased risk of certain cancers in persons conceived with assisted reproduction. We recently revealed substantial epigenetic differences in newborns conceived with ART, including DNA methylation differences in the BRCA1 promotor. Whether these epigenetic differences influence gene expression, or persist into older ages, or are associated with risk of cancer, are open questions. The oldest persons conceived with ART are now entering their late 30s, which enables us to address cancers beyond childhood. If there is an increased risk of breast cancer or other cancers we need to identify if ART procedures play a role, or if underlying conditions related to subfertility or adverse birth outcomes are associated with later risk of cancer. As only a fraction of women with hereditary breast cancer can be identified through the known variants of BRCA, we need to find additional predisposing genetic or epigenetic factors to identify women at higher risk. One piece of this puzzle is to establish whether epigenetic marks present at birth in cancer-associated genes persist into adulthood. 

Our research questions evolve around three themes, assessed in three work packages:

1. Registry based approach
2. Epigenetic analyses
3. Gene expression analyses

Our main objectives are: 

1. To determine if the risk of BRCA1 associated cancers, particularly breast cancer, is increased in persons conceived with ART.
2. To determine if epigenetic marks at birth in cancer risk-genes, particularly BRCA1, persist into early adulthood, and if accelerated biological aging is associated with risk of cancer.
3. To determine if epigenetic marks present at birth are associated with gene expression.