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

Abstract

BackgroundThe 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 methodsOur 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.ResultsTwelve 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.ConclusionInadequate 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.

Genetic counseling, genetic testing, and risk perceptions for breast and colorectal cancer: Results from the 2015 National Health Interview Survey

“…Universal population genetic testing for BC and CRC risk has been proposed, which would include asymptomatic individuals regardless of family history (Murray et al, 2018;Gabai-Kapara et al, 2014;Prince et al, 2017). Our results show that engagement with genetic services among such individuals is still relatively uncommon.…”

“…Cancer genetic testing of asymptomatic individuals with no personal cancer history is most commonly performed when there is a family history of cancer (Petrucelli et al, 2016). However, there has been emerging interest in instituting cancer genetic testing at the population level, including healthy individuals regardless of their cancer family history or a known pathogenic variant in a family member (Gabai-Kapara et al, 2014;Prince et al, 2017).…”

Evaluating parents’ decisions about next-generation sequencing for their child in the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening) study: a randomized controlled trial protocol

“…If they have requested information from either or both of the other categories (childhood-onset conditions with low or no medical actionability or adult-onset conditions with high medical actionability), they are scheduled for a third in-person study visit (visit 3) for disclosure by a medical geneticist and genetic counselor. All parents, regardless of their randomly assigned study group, complete two additional follow-up questionnaires after visit 2: the time 3 questionnaire, which collects data for a short-term follow-up within 2 weeks [ 30 , 31 ] of the return of results (visit 2 for those in the control arm and visit 3 for those in the decision arm), and the time 4 questionnaire, which collects data for a long-term follow-up 3 months after the participants’ final visit (Table 3 ).…”

The new genomic medicine service and implications for patients

“…It is unlikely that the NHS will be in a position to roll out population based genomic screening imminently due to a lack of evidence about the potential harms and benefits of embarking on genomic screening programmes and concerns regarding affordability and workforce requirements. 10 However, it should be recognised that this could be a direction that population screening takes for many conditions in future.…”