Varanasi: Researchers at Banaras Hindu University (BHU) have identified population-specific genomic risk markers for oral squamous cell carcinoma (OSCC)—the deadliest form of oral cancer—among communities in eastern Uttar Pradesh with high tobacco consumption. The findings could pave the way for earlier diagnosis and personalised screening strategies in high-burden regions where the use of smokeless tobacco products is deeply embedded in socio-economic and cultural practices.The study, which also identified three previously unreported genes linked to the disease, underscores the need for population-specific genomic tools, as existing global databases do not adequately represent the genetic diversity of North Indian communities.The research was led by Prof Pavan Dubey of the Faculty of Dental Sciences under the guidance of Prof Neelam Mittal. The team included Prof PG Naveen and Dr Rahul Agarwal from the Faculty of Dental Sciences, along with Prof Gyaneshwer Chaubey from the Department of Zoology.Researchers conducted a comprehensive analysis of DNA samples from 98 individuals from the Purvanchal region, including Varanasi, Gorakhpur, and neighbouring districts. The findings have been published in the scientific journal Bioinformation.Prof. Neelam Mittal said eastern Uttar Pradesh records one of the highest incidences of oral cancer in the country. According to cancer registry data, oral and tongue cancers are among the most common cancers among men in the region.She noted that the five-year survival rate ranges between 20% and 45%, primarily because most patients seek medical attention only after the disease has progressed to Stage III or IV. Smokeless tobacco products such as gutkha, khaini, zarda, and pan masala remain the primary drivers of the disease burden, with tobacco consumption rates in Uttar Pradesh significantly exceeding the national average.For the study, researchers adopted a dual genomic approach. Mitochondrial DNA profiling was carried out for all participants, followed by exome sequencing of 40 representative samples, comprising 20 patients and 20 control subjects. Additionally, 383 high-coverage genomes were analysed to compare findings with global population structures.Prof. Pavan Dubey said the 16223C polymorphism in the hypervariable segment of the mitochondrial genome was found significantly less frequently in patients with oral squamous cell carcinoma.“The absence of this polymorphism was associated with an 8.1-fold higher risk of developing oral squamous cell carcinoma,” he said.The study further revealed that individuals belonging to Western Eurasian haplogroups had a higher risk of developing the disease, while those with South Asian haplogroups—particularly M5a—showed a relatively protective trend.Researchers believe this genetic variant may help protect against tobacco-induced carcinogenesis by improving mitochondrial regulation and the body’s response to oxidative stress.Whole-genome sequencing also led to the identification of three novel genes that have not been previously documented in any major global cancer or population database. Combined with six genes already known globally, the total number of identified genes associated with the condition has now increased to nine.Lead author and geneticist Prof Gyaneshwer Chaubey said the findings highlight a significant gap in global genomic databases.“The genetic architecture of North Indian populations is not adequately represented in existing databases. In high-burden regions like Purvanchal, oral cancer is not merely a consequence of tobacco use but results from a complex interaction between genetic susceptibility and environmental factors,” he said.“Our findings reinforce the need to develop genomic tools tailored to our population. This work represents a small but significant step towards precision medicine,” he added.
