PerspectiveIn the Journals

Knowledge of individual risk did not increase colorectal cancer screening adherence

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October 20, 2014

Receipt of individualized genetic and environmental risk assessments did not increase colorectal cancer screening rates, even among study participants whose assessments showed they were at elevated risk for the disease, according to results of a randomized, controlled trial.

David S. Weinberg, MD, MSc, director of gastroenterology at Fox Chase Cancer Center in Philadelphia, and colleagues sought to evaluate whether a genetic and environmental risk assessment would improve screening adherence in 783 adults who were considered at average risk for colorectal cancer but were not regularly undergoing screening at baseline.

Researchers assigned 514 participants to undergo the risk assessment, which included analyses for methylenetetrahydrofolate reductase polymorphisms and serum folate levels. The other 269 study participants received usual care.

David S. Weinberg

Overall, 34% of study participants underwent colorectal cancer screening within 6 months.

Participants aged 70 to 79 years (OR=2.27; 95% CI, 1.32-3.9), as well as those aged 60 to 69 years (OR=1.29; 95% CI, 0.89-1.86), were more likely to undergo screening compared with those aged 50 to 59 years. Screening also was more likely among participants with greater knowledge about the process (OR=1.12; 95% CI, 1.01-1.24).

After adjustments for baseline participant factors, results showed participants who received the risk assessment were no more likely to undergo colorectal cancer screening than those who only received usual care (OR=0.88; 95% CI, 0.64-1.22).

Researchers conducted additional analyses after excluding 77 participants from the assessment cohort who had an unknown risk. Of the 437 remaining participants in the assessment cohort, 67 had an elevated risk for colorectal cancer and 370 had an average risk. Yet, participants found to be at elevated risk were less likely to undergo screening than average-risk participants in the risk assessment cohort (OR=0.6; 95% CI, 0.33-1.07).

After researchers adjusted for confounding risk factors, results still showed individuals found to be at elevated risk on the genetic and environmental risk assessment were less likely to undergo colorectal cancer screening than those shown to be at average risk (OR=0.75; 95% CI, 0.39-1.42).

Black participants were more likely to have an elevated risk for colorectal cancer compared with non-Hispanic whites (OR=5.92; 95% CI, 3.26-10.74). Participants who regularly took a multivitamin (OR=0.24; 95% CI, 0.13-0.44), as well as those who were knowledgeable about genetics and diet (OR=0.8; 95% CI, 0.7-0.9), were less likely to have an elevated risk.

“This large, randomized trial found no effect on colorectal screening rates in an average-risk population exposed to personalized genetic and environmental risk information,” Weinberg and colleagues concluded. “Further study is required to assess whether other such information and different means of presenting individualized results for common diseases like colorectal cancer will spur more healthy behaviors to reduce risk. The role of genetic and molecular testing to predict response to specific therapeutic options in health care delivery is increasing; however, the potential for similar testing to motivate behavioral change is less clear.”

Disclosure: The study was supported by grants from the NIH.

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Marwan Fakih

Marwan Fakih

Weinberg and colleagues report on a randomized clinical trial that investigated the impact of genetic and environmental risk assessment (GERA) on colorectal screening rates. The hypothesis behind this study is that an increased risk for colorectal cancer — determined by genetic and environmental risks — may improve the rate of colorectal cancer screening in the general population. To test this hypothesis, the investigators identified a population with normal risk for colorectal cancer who were overdue for screening. These patients were subsequently randomly assigned 2:1 to GERA or usual standard of care. The GERA population was tested for genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) to assess genetic risk and folic acid level to assess environmental risk. Higher-risk individuals within the GERA group were defined based on MTHFR polymorphism and lower folic acid levels. Patients in the standard-of-care arm and GERA group were advised to undergo screening measures for colorectal cancer and were provided with kits for fecal hemoccult. Patients within the GERA group were additionally advised if they were considered at high risk or normal risk for colorectal cancer based on MTHFR polymorphism and folic acid level.
Unexpectedly, the group of patients who were randomly assigned to GERA was no more likely to undergo colorectal screening than the standard-of-care group. Even more surprising is the fact that the group determined to be at high risk by GERA was no more likely to undergo screening than the group determined to be at normal risk by GERA.
Does this constitute a failure of genetic and environmental risk assessment to drive appropriate screening measures? We do not believe that this is the case. This study was limited by several factors. For one, the patient population was selected based on noncompliance to screening measures. However, the reason for non-compliance was not documented. It is unclear if some of the barriers to screening are modifiable and if this was a factor in the failure of the GERA strategy.
In addition, the GERA that is the subject of this study arguably has a minimal impact on risk for colorectal cancer. A relative risk increase of 1.5 to 2 is arguably small and with much controversy. Therefore, the impact of GERA in this particular study would have been expected to be small. Patients are much more motivated to undergo screening when the stakes for lack of screening are high.
Last, all patients on this study were approached with a central theme that consists of the fact that standard screening is recommended irrespective of their GERA. Therefore, patients approached through this study clearly will regard GERA as experimental and that screening is recommended regardless, leaving no great incentive for them for the extra effort toward colorectal cancer screening.
We have learned important messages from this study. Genetic and environment risk assessment is not likely to alter patients’ behavior toward screening assays if the genetic and environmental risk assessment leads to minimal increase in risk estimation. A GERA tool should provide a more precise risk assessment and stratification to be successful in the future. The perfect GERA tool should be based on genetic factors and environmental factors that not only drive compliance with screening strategy but also lead to a personalized approach of screening measures in terms of tools and frequency.

Marwan Fakih, MD
City of Hope Comprehensive Cancer Center

Disclosure: Fakih reports no relevant financial disclosures.