Polygenic scores to classify cancer risk

May 18, 2018, University of Michigan
Credit: CC0 Public Domain

Polygenic risk scores could be useful to stratify the risk of several cancers among patients in medical centers, allowing for the potential discovery of new associations between genes, disease and secondary effects, according to a University of Michigan study.

Researchers at U-M's School of Public Health conducted a phenome-wide association study in 28,260 unrelated, genotyped patients of recent European ancestry to evaluate whether polygenic risk scores for common cancers are associated with multiple phenotypes. The study used data from participants' .

The results demonstrate that polygenic risk scores, a summary score constructed based on results obtained from large population-based genome-wide association studies, can be potentially useful for risk stratification among patients in an academic medical center.

"This is just the tip of the iceberg. It shows the potential and the challenges with using phenome-wide associations," said Bhramar Mukherjee, the John D. Kalbfleisch Collegiate Professor of Biostatistics and professor of epidemiology at U-M's School of Public Health and associate director for Cancer Control and Population Sciences at the Rogel Cancer Center.

"Looking at the data, it was surprising to me how logical the secondary diagnosis associations with the risk were. When you look at the association plots of the risk scores against the phenome, I expected it to be a lot more noisy. I thought that there would be many spurious associations with random disease codes on the phenome level. It was also striking how results from population-based studies were reproduced using data from electronic health records, a database not ideally designed for specific research questions and is certainly not a population-based sample."

Lead author Lars Fritsche, assistant research scientist in the Department of Biostatistics at U-M's School of Public Health, agreed. For example, he said, a for squamous cell carcinoma—a common skin cancer form—showed a strong association for various forms of skin cancer, but also with actinic keratosis, a potentially precancerous skin lesion. Studying the sequence of diagnoses of the available patients' electronic health records can help to understand relationships like these.

Mukherjee said investigators will expand the analytic model to other lab tests and biomarkers to see if new associations with diseases across the phenome can be found there.

"What we are trying to do is to understand the pattern of concurrent diagnosis for a patient and determine if a cluster of diagnoses in the past is predictive of a disease state in the future," she said. "The temporal sequence of disease diagnoses and lab results along with genetic data are key to this scientific quest."

Researchers also plan to re-contact the initial subjects to collect data on their behavioral and environmental risk factors.

"There's enormous potential in terms of collecting behavioral data and integrating with molecular data," Mukherjee said. "Family history, stress data, anxiety data, sleep quality data, mental health data, so that you have a much more integrated vision of what is happening in a person's life."

"For future precision applications," Fritsche said, "it will be important to understand the challenges of such complex big data and to provide reliable approaches that can efficiently explore them, especially because we expect the amount of data to steadily increase over time."

The study, "Association of Polygenic Risk Scores for Multiple Cancers in a Phenome-wide Study: Results from the Michigan Genomics Initiative," will be published in the American Journal of Human Genetics.

Explore further: The genetic architecture of risk for autism spectrum disorder

More information: Lars G. Fritsche et al. Association of Polygenic Risk Scores for Multiple Cancers in a Phenome-wide Study: Results from The Michigan Genomics Initiative, American Journal of Human Genetics (2017). DOI: 10.1101/205021

Related Stories

The genetic architecture of risk for autism spectrum disorder

May 16, 2017
A new study of inherited genetic risk indicates that common genetic variations throughout the genome act in addition to rare, deleterious mutations in autism-associated genes to create risk for autism.

Multi-gene test predicts early heart disease risk

January 8, 2018
A risk score based on multiple genetic differences, or polygenic risk score, predicted significantly more cases of early-onset heart disease than standard tests for single genetic defects, according to new research in the ...

Risk of a second breast cancer can be better quantified in women carrying a BRCA mutation

March 21, 2018
The risk of a second breast cancer in patients with high-risk BRCA gene mutations can be more precisely predicted by testing for several other genetic variants, each of which are known to have a small impact on breast cancer ...

Study sheds light on genetic foundation of migraines

May 3, 2018
The nauseating, often debilitating, headaches affect 15-20 percent of adults in developed countries, yet they remain stubbornly hard to explain. Scientists know that migraines tend to run in families but aren't sure exactly ...

Antisocial behavior may be highly polygenic

October 9, 2017
(HealthDay)—Antisocial behavior (ASB) may be highly polygenic, with sex-discordant associations identified for some loci, according to a study published online Oct. 4 in JAMA Psychiatry.

Polygenic risk score may identify alzheimer's risk in younger populations

March 5, 2018
For the first time, an international team of scientists, led by researchers at University of California San Diego School of Medicine, have determined that an Alzheimer's disease (AD) polygenic risk score can be used to correctly ...

Recommended for you

Downward-facing mouse: Stretching reduces tumor growth in mouse model of breast cancer

May 22, 2018
Many cancer patients seek out gentle, movement-based stretching techniques such as yoga, tai chi and qigong, but does stretching have an effect on cancer? While many animal studies have attempted to quantify the effects of ...

Resetting the epigenetic balance for cancer therapy

May 22, 2018
Though mutations in a gene called MLL3 are common across many types of cancers, their relationship to the development of the disease has been unclear. Now, a Northwestern Medicine study has identified an epigenetic imbalance ...

Compound in citrus oil could reduce dry mouth in head, neck cancer patients

May 21, 2018
A compound found in citrus oils could help alleviate dry mouth caused by radiation therapy in head and neck cancer patients, according to a new study by researchers at the Stanford University School of Medicine.

Ice cream funds research showing new strategy against thyroid cancer

May 21, 2018
Anaplastic thyroid cancer is almost uniformly fatal, with an average lifespan of about 5 months after diagnosis. And standard treatment for the condition includes 7 weeks of radiation, often along with chemotherapy.

Bladder cancer model could pave the way for better drug efficacy studies

May 21, 2018
Understanding that not all bladder cancers are the same, researchers at the University of North Carolina Lineberger Comprehensive Cancer Center have created a tool that may help them to uncover why only a fraction of patients ...

Breath test breakthrough for early diagnosis of oesophageal and gastric cancer

May 18, 2018
A breath test can successfully detect oesophageal and gastric cancer and could be used as a first-line test for patients, say researchers.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.