Ahmedabad: A seven-year study involving 519 cancer patients has found that nearly half of the tumours showing microsatellite instability (MSI) — a marker of defects in DNA repair — were associated with Lynch syndrome, an inherited condition that increases the risk of several cancers.The findings provide India’s first molecular epidemiological evidence linking MSI and Lynch syndrome across multiple cancer types, potentially expanding opportunities for early diagnosis and cancer prevention, according to researchers.The study, ‘Pan-cancer prevalence of microsatellite instability and Lynch syndrome in India’ by Harsh Sheth, Jyoti Sadhwani, Bhawna Sirohi, and Senthilkumar Ramasamy among others has been published in Springer Nature journal, Familial Cancer.Dr Sheth, head of advanced genomics technology division at FRIGE-Institute of Human Genetics in Ahmedabad, said that the multi-centre study tested tumours from patients with 11 cancer types and found MSI in 25% of all tumours examined.“Among MSI-positive tumours, approximately 50% were linked to Lynch syndrome, including cases of colorectal, endometrial, ovarian, prostate and stomach cancer,” he said.Historically, screening for Lynch syndrome has focused largely on colorectal cancer, often relying on patients’ age at diagnosis and family history. This approach can miss individuals whose cancers occur in other organs or whose families have no obvious history of the disease.The researchers adopted a three-step approach: Testing tumours for MSI, conducting whole-exome sequencing of blood samples from patients with MSI-positive tumours to identify inherited mutations, and offering targeted genetic testing and counselling to relatives of those diagnosed with Lynch syndrome.The study found that mutations in the MLH1 gene accounted for 70% of Lynch syndrome cases. Two variants, c.306G>T and c.156delA, together accounted for 33% of cases. Researchers also identified geographical patterns associated with these variants: c.306G>T was enriched in North India, while c.156delA was enriched in Siddhpur, Gujarat.“The findings suggest that MSI testing could serve the dual purpose of helping identify patients who may benefit from immunotherapy and flagging those who require further assessment for hereditary cancer risk,” said Sheth.By extending screening beyond colorectal cancer, the study highlights an opportunity to identify hereditary cancer risk earlier and improve prevention for patients and their families, said researchers.
