Mumbai, Nov. 30 -- Tobacco chewers with multiple risky genetic variations develop oral cancer 10 to 20 years earlier than others who lack such genetic variations and chew similar amounts of tobacco, a study by the Centre for Cancer Epidemiology at the Tata Memorial Centre has revealed. The research was published on Saturday in Lancet Discovery Science journal eBioMedicine. Researchers at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) analysed DNA of 2,160 patients with buccal mucosa cancer, which affects the inner cheek, and 2,325 people without the disease, across an 11-year period from 2010 to 2021 to understand why oral cancer strikes earlier in certain people. They found that while chewing tobacco is still the biggest cause of oral cancer, some people have inherited genetic changes that significantly amplify the risk of developing the disease. The team identified several genetic "hotspots" where these risky variations occur. Changes at these locations can influence how the body responds to carcinogens, substances that can cause cancer by damaging a cell's DNA, leading to mutations. While the study revealed that risky changes near some genes could lead to cancer earlier, they found that changes near the NOTCH1 gene, which can lead to cancer as well as suppress the tumour gene, were particularly risky. Scientists then calculated a polygenic risk score (PRS), a measure that combines the effect of many small genetic risks. A high PRS score means a person has multiple risky genetic variations that, combined with tobacco chewing, can trigger cancer much earlier than in others with similar habits. The study showed that tobacco chewers with a high PRS developed buccal mucosa cancer about 10 years earlier than those with a low score. In some cases, the onset was nearly 20 years earlier....