A recent study conducted by Stanford Medicine has revealed that the gene sequences we inherit at birth can be strong predictors of the type of breast cancer we may develop later in life and how aggressive it might be. This new finding challenges the common belief that most cancers arise as a result of random mutations that accumulate over time. Instead, it suggests that our inherited gene sequences, known as our germline genome, play a significant role in determining whether potential cancer-causing mutations are detected and eliminated by the immune system, or if they go undetected and develop into cancer.
The study, published in Science and led by senior author Christina Curtis and lead author Kathleen Houlahan, highlights the importance of understanding the interaction between newly formed cancer cells and the immune system in order to better predict and combat breast tumors. It also sheds light on the complex interplay between inherited gene variants and cancer development, providing new insights into why some individuals remain cancer-free while others are more susceptible to developing the disease.
In contrast to somatic mutations that occur as cells divide and DNA is copied throughout our lives, germline mutations are inherited from our parents and can significantly influence our risk of developing cancer. While mutations in well-known cancer-associated genes such as BRCA1 and BRCA2 are commonly used to predict cancer risk, this study suggests that there may be many other germline mutations that are associated with future cancers. Identifying these additional gene variants could provide valuable information for assessing an individual’s risk of developing breast cancer.
The researchers focused on understanding how inherited DNA influences the evolution of tumors, particularly by examining the role of the immune system in detecting and eliminating cancer cells. By analyzing nearly 6,000 breast tumors, they discovered that individuals who inherited oncogenes with high epitope burdens, or a large amount of recognizable protein fragments, were less likely to develop certain aggressive breast cancer subtypes. However, tumors that managed to evade the immune system early in their development were found to be more aggressive and have a poorer prognosis.
The study’s findings suggest that there is a delicate balance between tumor cells and the immune system, with some tumors being eliminated early on by immune cells, while others develop mechanisms to evade detection and continue to grow. This insight could potentially inform strategies for therapeutic interventions and personalized cancer treatments in the future. By combining knowledge of the germline genome with the 11 subtypes of breast cancer identified by Curtis, clinicians may be able to improve treatment decisions, monitor for recurrence, and predict an individual’s risk of cancer from a simple blood sample.
Overall, this study represents a significant step towards understanding the complex factors that contribute to cancer development and progression, including the interplay between inherited gene variants, somatic mutations, and immune responses. By leveraging this knowledge, researchers and clinicians may be able to improve cancer risk assessment, develop personalized treatment strategies, and make progress towards more effective cancer therapies in the future.