How should I approach genetic testing for Lynch Syndrome in patients with a family history of colorectal or endometrial cancer?

Approach genetic testing for Lynch syndrome in patients with a family history of colorectal or endometrial cancer by first assessing their risk of carrying pathogenic variants in mismatch repair (MMR) genes, which are implicated in Lynch syndrome. This assessment should consider detailed family history, including first- and second-degree relatives with colorectal, endometrial, or related cancers, and use validated risk assessment tools such as the Manchester scoring system or CanRisk to estimate carrier probability ¹.

Patients meeting criteria based on family history or personal cancer history should be referred for genetic counselling and offered germline genetic testing using appropriate gene panels that include MMR genes (e.g., MLH1, MSH2, MSH6, PMS2) as recommended by the UK national genomic test directory ¹.

Pre-test counselling is essential to ensure informed consent and to discuss the implications of testing, including the possibility of identifying pathogenic variants that confer increased cancer risk and the impact on relatives ¹.

Genetic testing may be undertaken in mainstream clinical settings, such as oncology or gastroenterology multidisciplinary teams, to facilitate timely diagnosis and management ¹.

Following identification of a pathogenic variant, patients should be offered tailored surveillance and risk-reduction strategies, including consideration of daily aspirin to reduce colorectal cancer risk, as supported by NICE guidance ².

Overall, the approach integrates detailed risk assessment, appropriate genetic counselling, use of validated gene panels, and multidisciplinary coordination to optimize identification and management of Lynch syndrome in at-risk individuals (Coffin et al., 2019).