Decoding the Genetics of Disease Risk: Polygenic Risk Scores
Using PRS to Detect Cancer
Cancer is the second highest cause of death every year. Causing over 10 million people to die each year, that means every 1 in 6 people die from this intricate disease.
In this never-ending war against cancer, timing is everything. Early detection is one of the most critical factors in determining whether a person can live or die.
The reality is that there are numerous types of cancer, each behaving uniquely based on the organ it inhabits. Cancer subtypes exhibit surprising variations even within the confines of a single organ.
An example of detecting cancer in its early stage, where it’s crucial, is breast cancer. According to the American Cancer Society, the 5-year survival rate for localized breast cancer is 99%. But, when breast cancer has already spread to distant organs, that survival rate plummets to 27%. This contrast shows that the huge impact of catching cancer in its early days is super significant.
This is where Polygenic Risk Scores (PRS) enter this field. PRS offers a lifeline by providing individuals with crucial insights into their genetic predisposition to cancer. With this knowledge, individuals can take proactive steps toward early detection and prevention.
In modern medicine and genomics, the term “Polygenic Risk Score” (PRS) has been gaining more and more traction. It’s one of the tools in our journey to understand and predict the likelihood of developing complex diseases, such as cancer. In this article, we’ll dive into the complex details of PRS, how it works, its applications, and its challenges, shedding some light on how genetics plays a significant role in determining disease susceptibility.
Understanding the Complexity of Cancer
Cancer, a “multifaceted” and diverse disease, creates a massive challenge for medical researchers. Its complexity is shown by the fact that there are numerous types of cancer, each behaving differently based on the organ it originates in. Even within the same organ, cancer subtypes may exhibit significant variations. For example, breast cancer may share more similarities with lung or ovarian cancer than with other breast cancer subtypes.
But cancer isn’t solely about the malignant cells themselves; it involves a complex interaction between these cells, the patient’s body, and the surrounding tissue environment. This intricate web of interactions influences tumor growth and progression.
Deciphering Polygenic Risk Scores
The concept of Polygenic Risk Scores is at the core of understanding disease risk. These scores involve analyzing a person’s genetic makeup to estimate their susceptibility to complex diseases. Unlike monogenic conditions ( genetic disorders caused by mutations in a single gene) such as cystic fibrosis, complex diseases like cardiovascular diseases, Parkinson’s, and diabetes result from multiple genetic factors scattered throughout the genome.
How PRS Works
To understand how PRS works, let’s dive deeper into the process itself:
Step One: Identifying Risk Variants
Scientists compare the genetic profiles of individuals with a particular disease to the people who don’t have it. They would look for these specific genetic variants that occur more frequently in individuals with the disease. These variants are labelled as “risk variants.”
Step Two: Quantifying Risk
Each risk variant can increase or decrease a person’s risk of developing the disease. Which means they can have different magnitudes of impact from that disease. Some may substantially raise the risk, while others can have a milder effect.
Step Three: Calculating the PRS
The Polygenic Risk Score is computed by summing up the risk-increasing and risk-decreasing variants, considering their different impact levels. This calculation results in a numeric score that reflects an individual’s genetic predisposition to the disease.
Step Four: Personalized Risk Assessment
After assessing an individual’s PRS, if they test positive for a specific type of mutation associated with a particular disease, healthcare providers can offer personalized treatments or next steps. This approach can also help control the disease’s causes, progression, and effects.
Application in Disease Prevention and Management
Knowing your likelihood of developing a particular disease can be empowering. It enables individuals to take proactive steps towards prevention or early detection when treatment is often more effective. Additionally, PRS can be combined with other factors to predict disease progression and treatment response, offering a personalized approach to healthcare.
The Role of PRS in Research and Medicine
Polygenic Risk Scores play a crucial role in scientific research and clinical practice. They are utilized to assess shared genetic factors between different disease phenotypes, evaluate the clinical utility of genetic data, and inform experimental studies. Researchers often compare outcomes, such as gene expression and cellular responses to treatment, between individuals with low and high PRS values.
Companies like Illumina have been at the forefront of developing and implementing PRS testing. Illumina’s approach involves leveraging genetic data to assess an individual’s risk for complex diseases. However, there are some limitations and challenges associated with this technology.
Gaps in PRS Technology
One significant challenge with PRS is the potential for inaccuracies and false positives in gene detection. For example, a Polygenic Risk Score for coronary artery disease detection has a relatively low detection rate of 15% for a 5% false-positive rate. It could classify 5% of unaffected individuals as positive while missing 85% of affected individuals.
It’s crucial to emphasize that PRS is not a substitute for cancer detection through screening methods. It offers insights into disease risk but cannot replace established screening protocols. Furthermore, PRS carries uncertainty, as statistical imprecision and discrete cut-offs can impact risk assessment.
Additionally, PRS can be influenced by biases, affecting its performance and predictive accuracy. Patients must also consent to genome testing, which may not be universally embraced.
Another significant challenge is the underrepresentation of specific populations in PRS research. Most PRS development has focused on individuals of European descent, leaving gaps in our understanding of how PRS applies to other racial and ethnic groups. Some PRSs may exhibit reduced performance in people of non-European ancestry, potentially exacerbating health disparities.
Polygenic Risk Scores offer a promising avenue for understanding complex diseases and tailoring healthcare to individual genetic profiles. As research continues to evolve and expand to include more diverse populations, PRS may become an indispensable tool in preventing, detecting, and managing diseases like cancer.
Polygenic Risk Scores represent a breakthrough in our quest to unravel the genetic intricacies of disease risk. They provide a personalized disease prevention and management approach, offering insights into an individual’s susceptibility to complex diseases.
However, challenges and gaps in the technology and research must be addressed to ensure equitable access and accurate risk assessment for all populations. As we continue to decode the language of genes, the future of personalized medicine holds great promise, potentially revolutionizing how we approach healthcare.
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