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Prince AE, Cadigan RJ, Henderson GE, et al. Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review. Pharmgenomics Pers Med. 2017;10:49-60doi: 10.2147/PGPM.S123808.
Prince, A. E., Cadigan, R. J., Henderson, G. E., Evans, J. P., Adams, M., Coker-Schwimmer, E., Penn, D. C., Van Riper, M., Corbie-Smith, G., & Jonas, D. E. (2017). Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review. Pharmacogenomics and personalized medicine, 1049-60. https://doi.org/10.2147/PGPM.S123808
Prince, Anya E R, et al. "Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review." Pharmacogenomics and personalized medicine vol. 10 (2017): 49-60. doi: https://doi.org/10.2147/PGPM.S123808
Prince AE, Cadigan RJ, Henderson GE, Evans JP, Adams M, Coker-Schwimmer E, Penn DC, Van Riper M, Corbie-Smith G, Jonas DE. Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review. Pharmgenomics Pers Med. 2017 Feb 20;10:49-60. doi: 10.2147/PGPM.S123808. eCollection 2017. PMID: 28260941; PMCID: PMC5325104.
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Pharmgenomics Pers Med. 2017 Feb 20;10:49-60. doi: 10.2147/PGPM.S123808. eCollection 2017.

Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review.

Pharmacogenomics and personalized medicine

Anya E R Prince, R Jean Cadigan, Gail E Henderson, James P Evans, Michael Adams, Emmanuel Coker-Schwimmer, Dolly C Penn, Marcia Van Riper, Giselle Corbie-Smith, Daniel E Jonas

Affiliations

  1. Center for Genomics and Society.
  2. Center for Genomics and Society; Department of Social Medicine.
  3. Center for Genomics and Society; Department of Genetics; Carolina Center for Genome Sciences; Lineberger Comprehensive Cancer Center; Department of Medicine.
  4. Center for Genomics and Society; Department of Genetics.
  5. Cecil G. Sheps Center for Health Services Research.
  6. Department of Social Medicine.
  7. Center for Genomics and Society; School of Nursing, The University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
  8. Center for Genomics and Society; Department of Social Medicine; Department of Medicine.
  9. Center for Genomics and Society; Department of Medicine; Cecil G. Sheps Center for Health Services Research.

PMID: 28260941 PMCID: PMC5325104 DOI: 10.2147/PGPM.S123808

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.

Keywords: Lynch syndrome; general population; genetic screening; systematic review; targeted next-generation sequencing

Conflict of interest statement

Disclosure The authors report no other conflicts of interest in this work.

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