Abstract
Background
The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research.
Materials and methods
Our 2014–2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes.
Results
Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23–0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09–0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation.
Conclusion
Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need for data that directly compare benefits and harms.
Acknowledgments
Research reported in this publication was supported by the National Institutes of Health through the National Human Genome Research Institute under Award Numbers P50HG004488 (all authors, except DP) and U01HG006487 (GEH and JPE), the National Heart, Lung, and Blood Institute under Award Number HL105493 (GC-S), and the US Department of Health and Human Services through the Health Resources and Services Administration under Award Number 5-D33-HP25771 (DP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors participated in the conception and design of the systematic review, the analysis of the data, and the drafting and revising of the manuscript. The review’s literature searches were conducted by Christiane Voisin, MLS. Additional data analysis support was received from Roberta Wines, Gabriel Lázaro-Muñoz, Alexi McHugh, and Malika Roman Isler. We also thank the two anonymous reviewers for their helpful comments and suggestions to improve this manuscript.
Disclosure
The authors report no other conflicts of interest in this work.