Mumbai: A major genetic study by the Centre for Cancer Epidemiology at the Tata Memorial Centre, has found that some tobacco chewers in India are born with genes that make them develop oral cancer 10 to 19 years earlier than others who chew similar amounts of tobacco.
A major genetic study by the Centre for Cancer Epidemiology at the Tata Memorial Centre, has found that some tobacco chewers in India are born with genes that make them develop oral cancer 10 to 19 years earlier than others who chew similar amounts of tobacco. (stock.adobe.com)
The research, published on Saturday in Lancet Discovery Science journal eBioMedicine, is India’s largest study of buccal mucosa cancer, which affects the inner cheek. Researchers at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) analysed the DNA of 2,160 patients with this cancer 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.
Researchers collected patients’ medical histories, lifestyle information and blood samples to study their DNA. They found that while smokeless 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 and 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 were particularly risky. The NOTCH1 gene is known to both lead to cancer and suppress the tumor gene, making a particularly volatile spot where a particular kind of mutation can heighten the risk of cancer. These results were further confirmed through meta-analyses, a study of several independent studies analysing the DNA of European and Taiwanese populations.
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.
Author and director of ACTREC, Dr Pankaj Chaturvedi, said, “If these findings are to make a real difference, they must translate into policy action. Tobacco chewing increases cancer risk 26 times; for people with high genetic susceptibility, that risk doubles again.”
The study’s corresponding author, Dr Sharayu Mhatre, said that buccal mucosa and other mouth cancers are particularly common in India due to widespread use of smokeless tobacco. “To prevent these cancers, we must recognise that smokeless tobacco, especially commercially prepared gutka and areca-nut mixes, make up the strongest risk factor. We saw a 24% rise of cases among chewers with high genetic risk,” she said.
Among tobacco chewers, the chance of developing buccal mucosa cancer between ages 40–74 was 0.6% for those with the highest genetic risk and 0.3% for those with the lowest risk. High-risk chewers were also estimated to get cancer about 10 years earlier than low-risk chewers.
Author and director of the Centre for Cancer Epidemiology, Dr Rajesh Dikshit, said “Genes don’t work in isolation. They interact with tobacco, alcohol, pollution and other factors. But identifying high-risk individuals allows us to support them by helping them quit tobacco, organise early screenings more often to prevent cancer.”
The study notes that in India, Maharashtra has a mid-level tobacco use rate of 26.6%, but Mumbai continues to record high numbers of inner-cheek and mouth cancers linked to khaini, mishri and areca-nut products. In the city, the rate of mouth cancer per 100,000 people was 10.3 among men and 4 among women.
E-Paper
