Lynch Syndrome: Its Phenotypic and Genotypic Heterogeneity

Abstract

It is estimated that approximately 3–5% of all colorectal cancers may manifest the Lynch syndrome while its familial adenomatous polyposis counterpart accounts for less than 1% of the total colorectal cancer burden. Familial aggregation constitutes approximately 20% of all colorectal cancer occurrences. What does this mean to the geneticist, diagnostician, and ultimately the high-risk patient? Clearly, family history is the key, and when germline pathogenic mutations are identified within a family, one is then in the enviable position of providing a significant reduction in patients’ cancer morbidity and mortality through highly-targeted screening and management. Confounders for each high-risk family will be the syndrome’s phenotypic and genotypic heterogeneity, and therein it will be best comprehended through study of its natural history. In some cases the syndrome’s complexity may be beyond the physician’s knowledge, and help will then be available through referral to genetic counselors or centers of cancer genetics expertise. Finally, basic science and clinical studies on high-risk families harbor enormous opportunities to uncover etiology and pathogenesis which may ultimately translate into cancer prevention in both hereditary and sporadic forms of cancer.

Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

“…Our results support the outcomes of previous studies regarding deficiency in knowledge and awareness about Lynch syndrome and Lynch-associated tumour types [ 19 , 20 ]. The syndrome’s complexity, which involved not only colorectal cancer aggregation in a family but also malignancies in the endometrium, ovary, stomach, small bowel, pancreas, liver and biliary tract, upper urinary epithelial tract, skin, brain and possibly breast, may serve as confounders for diagnosing high-risk families [ 26 ]. In addition, the inconsistent nomenclature used for the syndrome can lead to poor recognition and referral of appropriate patients who would benefit from cancer genetics services.…”

Lynch-Syndrom, familiäre adenomatöse Polyposis und andere Polyposis-Syndrome – chirurgischer Blickwinkel

“…Sofern in der Eigenanamnese bereits neoplastische Veränderungen aufgetreten sind, spielen der Organbezug und das Alter eine ebenso wegweisende Rolle wie die Familienanamnese (zu der Klassifikation der Familienanamnese siehe die Artikel von Aretz [4] und Lynch [5] in diesem Themenheft). Um den Verdacht auf das Vorliegen eines Lynch-Syndroms (LS) zu erhärten, kann präoperativ die Mikrosatelliteninstabilität (MSI) in der Tumorbiopsie oder alternativ das Tumorgewebe anderer Karzinome des Patienten oder betroffener Familienangehöriger untersucht werden.…”