Genetic Factors Behind Early Oral Cancer in Indian Tobacco Chewers

Context:

A major new study by the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), part of Tata Memorial Centre (TMC), Mumbai, recently uncovered why some Indian tobacco chewers develop oral cancer much earlier than others. The study provides the first clear genetic explanation for inter-individual variation - why two persons with similar tobacco habit may have very different disease outcomes.

About Oral Cancer:

· Oral cancer is a type of cancer that starts in the mouth and can develop on the lips, tongue, gums, cheeks, floor of the mouth, or roof of the mouth.

· It occurs when cells in the mouth develop mutations in their DNA, causing them to grow and multiply out of control, forming a tumour.

· While often presenting as a painless, persistent lump, red or white patch, or ulcer, it is a serious condition that can spread and become fatal if not detected and treated early.

· Oral cancer remains a serious public health problem in India: annually about 1,41,342 cases are recorded.

Key Genetic Findings:

Identification of Key Genetic Markers

· The study identified specific genetic loci on chromosomes 5 and 6 associated with a significantly higher risk of oral cavity cancer.

· These loci are located near genes such as:

o CLPTM1L–TERT (linked to telomere length and cell aging)

o HLA-DRB1 and HLA-DQB1 (important for immune function)

o CEP43 (involved in cellular structural functions)

High Genetic Susceptibility Leads to Earlier Onset

· Researchers calculated a Polygenic Risk Score (PRS) for participants.

· Tobacco chewers with high PRS developed Buccal Mucosa cancer 10 years earlier than those with low PRS.

Increased Cancer Risk Among Tobacco Chewers

· Tobacco chewing alone increases oral cancer risk 26-fold.

· Among tobacco chewers, individuals with high-risk genetic markers have double the risk of developing oral cancer compared to those with low genetic risk.

Implications for Public Health and Policy:

Aspect	Implication
Screening & Early Detection	Genetic risk profiling and PRS-based screening can help identify high-risk individuals for frequent monitoring, even before symptoms manifest.
Targeted Preventive Strategies	Focused anti-tobacco campaigns and tailored counselling for individuals with high genetic risk — especially in rural and high-prevalence areas.
Precision Medicine & Treatment	Knowledge of genetic mutations enables personalised therapy, targeted drugs, and more effective treatment regimes.
Policy Reinforcement	Reinforces the urgency of tobacco control measures, especially on smokeless tobacco and betel quid — primary contributors to oral cancer in India.