1. Green, Chuck

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Casting the current so called one-size-fits-all method of identifying colorectal cancer as imprecise-not to mention unreliable-public health researchers at Fred Hutchinson Cancer Research Center recently drafted a roadmap of sorts for the future use of precision screening for the condition.

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Fred Hutch epidemiologist Ulrike "Riki" Peters, PhD, MPH, shared senior author of the study, noted her team has a solid approach in showing how it can integrate environmental, lifestyle, and [inherited] genetic data to predict risk.


"It made sense to try to combine this growing knowledge to investigate if we can use it to predict disease," she stated. Currently, of course, only age and family history are used to define who should go when for screening.


While calling it an "an excellent study that adds to our understanding of colorectal cancer risk prediction, we're far from understanding the real-world clinical significance," remarked Daniel Reuland, MD, MPH, Director of the Carolina Cancer Screening Initiative at the University of North Carolina School of Medicine. Using models to adjust the recommended age for initiating colorectal cancer screening may matter for some at the extremes of risk, Reuland noted; the highest versus lowest 10 percent, but most people will fall much closer to the average risk.


So, either way, for most, a more "precise" recommended age of screening initiation would differ by current recommendations by just a few years, he explained.


Pankaj Vashi, MD, Chair, Department of Medicine for Cancer Treatment Centers of America, described the risk prediction model as an "exciting concept that, in theory, makes a lot of sense." But he believes it has too many variables that can be difficult to identify and implement. The effectiveness of this model, he continued, hinges on the ability of physicians and researchers to gather more data points and develop the appropriate algorithms to process the information and method of dissemination so that it can be administered effectively at the bedside and beyond.


Peters acknowledged her team's approach is making it a little more complicated for physicians and patients. "However, if well-implemented in the electronic health record, this can be streamlined."


Analyzing Recommendations

Starting at age 50, those at average risk should get a colonoscopy sigmoidoscopy, or other test, according to current screening guidelines. Based on a risk prediction model, the new approach isn't so much cookie cutter and considerably more nuanced. In order to ascertain when an individual should begin colorectal cancer screening-the country's third leading cause of cancer death-it relies on personal risk factors and genetic data.


Though conceding the current approach might not be perfect, through clinical research, it has demonstrated its effectiveness, commented Vashi. "Baseline screening at age of 50 is a well-accepted screening strategy throughout the medical community. Primary care physicians now have the screening schedules on their EHR and compliance is easily monitored, Vashi said.


The model recommends some people at high risk start screening as early as age 40 and some at low risk to wait until their 60s.


Patient data drawn from a number of colorectal cancer studies done between 1992 and 2005, all of which are associated with the Genetics and Epidemiology and Colorectal Cancer Consortium (GECCO) and the Colorectal Transdisciplinary study (CORECT), were utilized by a battery of epidemiologists and biostatisticians.


Data from about 20,000 people-roughly half with the disease and half without-were used to build and validate their risk-prediction model. The model used family history of disease, lifestyle, and environmental risk factors, and genetic variants associated with the disease to determine colorectal cancer risk.


"As the genetic background differs, we need to test the model in each ancestral group to ensure we use the right genetic markers," said Peters.


Based on their findings, the one-size-fits-all initial screening age of 50 is either too early or too late for many. Recommended for much earlier screening were men in the highest 10 percent of risk, according to the new model.


However, Gregory Cooper, MD, Division of Gastroenterology at University Hospitals Cleveland Medical Center, said he'd be careful about delaying screening until validated and refined. "We don't fully understand the implications of collecting genetic data in all comers. We might be falsely labeling patients as high or low risk."


In the meantime, among women, findings were similar. It was recommended that those with a family history of colorectal cancer, on top of high environmental, lifestyle, and genetic vulnerability initiate screening 4 years earlier, when they're 46. Furthermore, it was deemed acceptable for those stratified to the lowest 10 percent of risk, even with a family history, wait until 59 years of age.


For their model, researchers used 19 evidence-based lifestyle/environmental risk factors including, for instance, smoking, alcohol consumption, and physical activity. The team ascertained genetic risk scores by studying 63 small genetic variations at 49 known colorectal cancer loci. They'd been identified through association studies conducted by cancer research consortiums such as GECCO and CORECT.


Research showed the environmental and lifestyle risk factors were just as important as inherited genetic variations associated with colorectal cancer.


"These researchers have done terrific work in developing these models. However, the road between these findings and improved health is long," noted Cooper.


Chuck Green is a contributing writer.