Genetic and environmental risk assessment and colorectal cancer screening in an average-risk population: a randomized trial

Ann Intern Med. 2014 Oct 21;161(8):537-45. doi: 10.7326/M14-0765.


Background: New methods are needed to improve health behaviors, such as adherence to colorectal cancer (CRC) screening. Personalized genetic information to guide medical decisions is increasingly available. Whether such information motivates behavioral change is unknown.

Objective: To determine whether individualized genetic and environmental risk assessment (GERA) of CRC susceptibility improves adherence to screening in average-risk persons.

Design: 2-group, randomized, controlled trial. ( NCT0087360).

Setting: 4 medical school-affiliated primary care practices.

Participants: 783 participants at average risk for CRC who were not adherent to screening at study entry.

Intervention: Participants were randomly assigned to usual care or GERA, which evaluated methylenetetrahydrofolate reductase polymorphisms and serum folate levels. On the basis of prespecified combinations of polymorphisms and serum folate levels, GERA recipients were told that they were at elevated or average risk for CRC.

Measurements: The primary outcome was CRC screening within 6 months of study entry.

Results: Overall screening rates for CRC did not statistically significant differ between the usual care (35.7%) and GERA (33.1%) groups. After adjustment for baseline participant factors, the odds ratio for screening completion for GERA versus usual care was 0.88 (95% CI, 0.64 to 1.22). Within the GERA group, screening rates did not significantly differ between average-risk (38.1%) and elevated-risk (26.9%) participants. Odds ratios for elevated- versus average-risk participants remained nonsignificant after adjustment for covariates (odds ratio, 0.75 [CI, 0.39 to 1.42]).

Limitation: Only 1 personalized genetic and environmental interaction and 1 health behavior (CRC screening) were assessed.

Conclusion: In average-risk persons, CRC screening uptake was not positively associated with feedback from a single personalized GERA. Additional studies will be required to evaluate whether other approaches to providing GERA affect screening utilization differently. These findings raise concern about the effectiveness of moderately predictive assessment of genetic risk to promote favorable health care behavior.

Primary funding source: National Institutes of Health.

Trial registration: NCT00087360 NCT00087360.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Early Detection of Cancer / statistics & numerical data*
  • Female
  • Folic Acid / blood
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Patient Compliance*
  • Polymorphism, Genetic
  • Precision Medicine
  • Risk
  • Risk Assessment*


  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)

Associated data