Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome): An Emerging Public Health Concern

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genes that confer increased lifetime risks for colorectal, endometrial, and other cancers. Lynch syndrome accounts for only 3%-5% of colorectal cancer cases; however, most patients with Lynch syndrome are not diagnosed, leading to missed opportunities for enhanced surveillance and preventive interventions.

This study examined the molecular genetics, epidemiology, and shortcomings of conventional, selective screening strategies for Lynch syndrome. Universal tumor testing using MMR immunohistochemistry (IHC) or microsatellite instability (MSI) analyses is recommended for all newly diagnosed colorectal and endometrial cancers, with reflex BRAF/methylation testing applied to distinguish likely sporadic cases. We also need to consider essential components of coordinated Lynch syndrome management, including cascade screening of family members, electronic health record (EHR) integration, multidisciplinary care teams, and public education. Selective screening for Lynch syndrome, based on the age or family history, misses many cases, whereas universal tumor testing is more cost-effective for identifying more patients. In addition to genetic counseling, surveillance colonoscopy, prophylactic surgical measures, and psychosocial support, we must provide equitable access to these services for all potentially affected patients. Advances in technology, such as circulating tumor DNA (ctDNA) assays and polygenic risk scores, represent new methods for cancer screening and risk stratification.

In summary, a coordinated, equity-centric public health model for Lynch syndrome should incorporate universal tumor testing, cascade screening, integration of clinical workflows, and community outreach. This framework could potentially turn the "underrecognized" aspect of Lynch syndrome into a "largely preventable" cancer syndrome. The proposed model could also represent a way to develop a broader strategy for other hereditary cancer syndromes, as future research focuses on scalable implementation, real-world cost-effectiveness, and genomic population screening.