What researchers call “the largest proteomic study in the world” could lead to new clinical laboratory assays for determining genetic risk for multiple cancers
Examining blood proteins may be superior to clinical information in determining an individual’s risk for developing multiple diseases. That’s according to a new study conducted by researchers from the UK, America, and Germany who determined that measuring thousands of proteins from a single drop of blood can predict the onset of several illnesses.
The findings may provide clinical laboratories and physicians with new assays to more accurately predict an individual’s risk for more than 60 diseases.
“With data on genetic, imaging, lifestyle factors and health outcomes over many years, this will be the largest proteomic study in the world to be shared as a global scientific resource,” said Naomi Allen, MSc, DPhil, chief scientist at UK Biobank and professor of epidemiology, University of Oxford, in a UK Biobank news release. “These combined data could enable researchers to make novel scientific discoveries about how circulating proteins influence our health, and to better understand the link between genetics and human disease.”
“Measuring protein levels in the blood is crucial to understanding the link between genetic factors and the development of common life-threatening diseases,” said Naomi Allen, MSc, DPhil (above), chief scientist at UK Biobank and professor of epidemiology, University of Oxford, in a news release. With further study, this research could lead to new clinical laboratory assays that help physicians predict an individual’s risk for certain diseases including many forms of cancer. (Photo copyright: UK Biobank.)
Protein Signatures Outperform PSA Testing
To conduct their research, the team collected data from the UK Biobank Pharma Proteomics Project (UKB-PPP). This initiative is “one of the world’s largest studies of blood protein concentrations” and “aims to significantly enhance the field of ‘proteomics,’ enabling better understanding of disease processes and supporting innovative drug development,” according to the Biobank’s website.
The scientists analyzed the values of approximately 3,000 plasma proteins among 41,931 participants in the UKB-PPP. They examined the 10-year potential of developing certain diseases by measuring the plasma proteome and linking those observations to incident cases noted in electronic health records (EHRs).
The team specifically looked at the pathology types for several illnesses and utilized advanced techniques to identify a signature of proteins associated with those various diseases. They found their protein-based model exceeded traditional prediction methods when comparing the models with polygenic risk scores.
“We are therefore extremely excited about the opportunities that our protein signatures may have for earlier detection and ultimately improved prognosis for many diseases, including severe conditions such as Multiple myeloma and idiopathic pulmonary fibrosis,” she added. “We identified so many promising examples; the next step is to select high priority diseases and evaluate their proteomic prediction in a clinical setting.”
Identifying Individuals at High Risk for Certain Diseases
Of the thousands of known proteins in humans, the team focused on about 20 proteins found in blood. With as few as five proteins and as many as 20, they were able to do a risk assessment on 67 diseases, including:
The model could prove to be beneficial in the development of new therapies for certain diseases.
“A key challenge in drug development is the identification of patients most likely to benefit from new medicines. This work demonstrates the promise in the use of large-scale proteomic technologies to identify individuals at high risk across a wide range of diseases, and aligns with our approach to use tech to deepen our understanding of human biology and disease,” said Robert Scott, vice president and head of human genetics and genomics, GSK, and co-lead author of the study in the UCL news release.
“Further work will extend these insights and improve our understanding of how they are best applied to support improved success rates and increased efficiency in drug discovery and development,” he added.
“We are extremely excited about the opportunity to identify new markers for screening and diagnosis from the thousands of proteins circulating and now measurable in human blood,” said Claudia Langenberg, PhD, director of the Precision Healthcare University Research Institute (PHURI) at Queen Mary University of London and professor of computational medicine at the Berlin Institute of Health, in the UCL news release. “What we urgently need are proteomic studies of different populations to validate our findings, and effective tests that can measure disease relevant proteins according to clinical standards with affordable methods.”
More research and studies are needed before the protein-based model can be used to predict disease in clinical settings. However, the model could someday provide clinical laboratories, pathologists, and physicians with new assays that more accurately forecast an individual’s risk for certain illnesses.
In the same way that BRCA1 and BRCA2 mutations helped pathologists identify women with increased breast cancer risks in the late 1990s, this new study isolates an additional 72 mutations medical laboratories may soon use to diagnose breast cancer and assess risk factors
For 20 years genetic scientists, anatomic pathologists, and medical laboratories have employed the BRCA1/BRCA2 genes to identify women at higher risk for breast cancer. And, because pathologists receive a high number of breast biopsies to diagnose, physicians and clinical laboratories already have collaborative experience working with genetic mutations supported by ample published evidence outlining their relationship with cancer.
Now, a global research study is adding 72 more mutations to the list of mutations already known to be associated with breast cancer.
In coming years, physicians and anatomic pathologists can expect to use the knowledge of these 72 genetic mutations when diagnosing breast cancer and possibly other types of cancers in which these mutations may be involved.
New Precision Medicine Tools to Improve Breast Cancer Survival
Combining the efforts of more than 550 researchers across 300 institutions and six continents, the OncoArray Consortium analyzed the DNA of nearly 300,000 blood samples. The analysis included samples of both estrogen receptor (ER-positive and ER-negative) cases.
Taken from a study published in the British Journal of Cancer, the graph above illustrates “proportions of familial risk of breast cancer explained by hereditary variants.” It is expected that anatomic pathologists will eventually incorporate these genetic variants into diagnostic test for breast and other cancers. (Graphic copyright: British Journal of Cancer.)
The results of their research were published in two separate studies: one in the scientific journal Nature and the other in Nature Genetics. The studies outlined 72 newly isolated genetic mutations that might help quantify the risk of a woman developing breast cancer in her lifetime.
Among the 72 mutations, seven genes were specifically associated with ER-negative cases. ER-negative breast cancer often fails to respond to hormone therapy. Thus, this discovery could be crucial to developing and administering precision medicine therapies tailored to specific patients’ physiologies and conditions. Treatments that improve patient outcomes and overall survival rates in ER-negative and ER-positive breast cancers.
Genetics Could Help Clinical Laboratories Wage War on All Cancers
According to data published by the Centers for Disease Control and Prevention (CDC), breast cancer is the most common form of cancer among women of all races. It’s the second-leading cause of all cancer deaths among most races and first among Hispanic women.
In the past, it was estimated that 5-10% of breast cancers were inherited through the passing of abnormal genes. However, Lisa Schlager, Vice President of community affairs and public policy for FORCE (Facing Our Risk of Cancer Empowered), told CNN, “This new information may mean that that estimate is low.” FORCE is a national nonprofit organization dedicated to fighting hereditary breast, ovarian, and related cancers.
Schlager calls upon health systems to “embrace the ability to use genetic information to tailor healthcare by providing affordable access to the needed screening and preventive interventions.” As precision therapy and genetic analysis continue to shape the way patients are treated, medical laboratories will play a significant role in providing the information powering these innovative approaches.
Identifying Women at Increased Risk for Breast Cancer
Peter Kraft, PhD, Professor of Epidemiology at Harvard’s T.H. Chan School of Public Health, and a study author, told CNN, “Taken together, these risk variants may identify a small proportion of women who are at three-times increased risk of breast cancer.”
Kraft notes that samples were sourced from women of primarily European ancestry. Further study of other ethnic populations could lead to yet more mutations and indicators for cancers more common outside of the European region.
Research authors also highlight the importance of continued standard screening, such as mammograms. However, they suggest that genetic mutations, such as those found in the OncoArray study, might be used to highlight high-risk individuals and screen sooner, or conduct more in-depth genetic analyses, to catch potential cancer cases earlier and improve outcomes.
“Many women are offered mammogram screening when they are middle-aged,” Georgia Chenevix-Trench, PhD, co-author of the Nature Genetics study and researcher at the QIMR Berghofer Medical Research Institute in Australia, told LabRoots. “But if we know a woman has genetic markers that place her at higher risk of breast cancer, we can recommend more intensive screening at a younger age.”
Anatomic pathologists and clinical laboratories can use these new insights to offer increased options for oncologists and physicians on the front lines of the battle against cancer. While the list of genetic mutations related to cancer is far from complete, each added mutation holds the potential to power a new treatment, improve early detection rates, and improve survival rates of this global killer.
Hot competition for genetic testing market share is a signal to medical laboratories to ramp up their molecular and genetic testing capabilities
Financial analysts see something of an “old west” style shootout on the horizon for genetic testing in the clinical laboratory testing market. Market leaders in next-generation gene sequencing are prepared to use acquisitions to build dominant shares in a gene testing market that experts say could hit $25 billion by 2022.
These two market leaders in DNA sequencing equipment have played important roles in revolutionizing genetic testing. Now, they intend to stake out a share of the fast-growing genetic diagnostics market themselves, a recent Businessweek story reported. (more…)
