Background & aims

Relative risk of colorectal cancer (CRC) decreases with age among individuals with a family history of CRC. However, no screening recommendations specify less frequent screening with increasing age. We aimed to determine whether such a refinement would be cost effective.

Methods

We determined the relative risk for CRC for individuals based on age and number of affected first-degree relatives (FDRs) using data from publications. For each number of affected FDRs, we used the Microsimulation Screening Analysis model to estimate costs and effects of colonoscopy screening strategies with different age ranges and intervals. Screening was then optimized sequentially, starting with the youngest age group, and allowing the interval of screening to change at certain ages. Strategies with an incremental cost effectiveness ratio below $100,000 per quality-adjusted life year were considered cost effective.

Results

For people with 1 affected FDR (92% of those with a family history), screening every 3 years beginning at an age of 40 years is most cost effective. If no adenomas are found, the screening interval can gradually be extended to 5 and 7 years, at ages 45 and 55 years, respectively. From a cost-effectiveness perspective, individuals with more affected FDRs should start screening earlier and at shorter intervals. However, frequency can be reduced if no abnormalities are found.

Conclusions

Using a microsimulation model, we found that for individuals with a family history of CRC, it is cost effective to gradually increase the screening interval if several subsequent screening colonoscopies have negative results and no new cases of CRC are found in family members.

Purpose

Family history of colorectal cancer (CRC) is a known risk factor for CRC and encompasses both genetic and shared environmental risks.

Methods

We conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening.

Results

We found high heterogeneity in family-history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than the commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family-history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC but no evidence for differential adenoma location or adenoma progression by family history. Limited data regarding the natural history of CRC by family history suggest a differential age or stage at cancer diagnosis and mixed evidence with respect to tumor location. Adherence to recommended colonoscopy screening was higher in people with a family history of CRC.

Conclusion

Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk for CRC.

The Evaluation of Genomic Applications in Practice and Prevention Working Group was first convened in 2005 to develop and test evidence-based methods for the evaluation of genomic tests in transition from research to clinical and public health practice. Over the ensuing years, the Working Group has met 26 times, publishing eight recommendation statements, two methods papers, and one outcomes paper, as well as planning and serving as technical experts on numerous associated systematic reviews. Evaluation of Genomic Applications in Practice and Prevention methods have evolved to address implications of the proliferation of genome-wide association studies and are currently expanding to face challenges expected from clinical implementation of whole-genome sequencing tests. In this article, we review the work of the Evaluation of Genomic Applications in Practice and Prevention Working Group over the first 8 years of its existence with an emphasis on lessons learned throughout the process. It is hoped that in addition to the published methods of the Working Group, the lessons we have learned along the way will be informative to others who are producers and consumers of evidence-based guidelines in the field of genomic medicine.

The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one's biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.