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Gene insights into oral cancer

A member of the research team at the National Institute of Biomedical Genomics, Kalyani

New Delhi, Dec. 1: A team of Indian scientists has identified five new genes that contribute to oral cancer, a disease linked to the consumption of tobacco and betel quid.

Researchers at the National Institute of Biomedical Genomics (NIBG) at Kalyani, Bengal, and the cancer research wing of the Tata Memorial Hospital (TMH), Navi Mumbai, found the genes through genome scans of tumour tissues of 110 oral cancer patients.

Three of the five genes interfere with the body’s natural tumour-suppressing mechanisms, while the other two genes appear to increase the risk of cancer by influencing tobacco-consumption behaviour, possibly raising the levels of addiction to smoking or chewing tobacco.

“We’ve found five genes. When altered, each in its own way appears to play a critical role in the complex process that drives normal tissues of the mouth into tumours,” NIBG director Partha Majumder told The Telegraph.

Majumder and his team-mates have described their findings in a paper to be published tomorrow in the journal Nature Communications.

Their study is part of a global research initiative called the International Cancer Genome Consortium, launched three years ago to decipher the deep genome biology of some 50 types of tumours.

The Indian arm of the consortium is focused on oral cancer, the leading cancer among men in this country. Cancer experts estimate that about 260,000 people develop oral cancer across India each year. Tobacco smokers have a 27-time higher rate of oral cancer than non-smokers.

While genes linked to the progression of normal cells into tumour cells have been known since the 1970s, cancer researchers have spent the past decade trying to systematically catalogue the genes altered in specific types of tumour tissues.

The research team found that five genes were frequently altered in 10 per cent to 22 per cent of the patients, figures statistically significant to indicate an association with the cancer.

“We expect these new genes to help us understand better the biological pathways that lead to oral cancer and perhaps to develop new therapies,” said Majumder, whose genomics laboratory is located at the Netaji Subhash Sanitorium in Kalyani, once a refuge for tuberculosis patients.

Alterations in three of the genes — USP9X, MLL4, and ARID2 — appear to obstruct the natural tumour-suppressing mechanisms that kill cells that have acquired genetic damage and threaten to turn into tumours.

The other two genes — UNC13C and TRPM3 — are both associated with processes involving neurotransmitters in the brain.

The scientists speculate that the alterations in these genes may increase the level of satisfaction that people derive from either smoking or chewing tobacco. And the heightened satisfaction may increase the degree of addiction and thus raise the risk of cancer.

The study has also suggested that patients with oral cancer who have alterations in the MLL4 gene have a significantly longer disease-free survival period than patients who do not, although the scientists caution this should be treated as a preliminary finding.

The Indian study has evoked interest from genomics researchers elsewhere. “This will be an important contribution to cancer genomics,” Francis Collins, director of the National Institutes of Health in the US, said in an email to Majumder.

The study has for the first time helped classify oral cancers into three types of molecular subgroups depending on which sets of genes are altered.

It is still unclear how these subgroups may be related to response to therapy or progression of the illness.

But a senior cancer biologist scientist said molecular sub-grouping in other tumour tissues, such as breast cancer, have helped researchers tailor more effective anti-cancer therapies for specific sets of patients.

While oral cancer primarily presents itself as tongue cancer in the West, it predominantly affects the lining of the mouth, lower gum and other regions of the oral cavity in India.

“The characterisation of a large sample of an oral cancer subtype common in India and rare in the West provides a unique contribution to the literature on head and neck squamous cell carcinomas (cancers),” wrote Carolyn Hutter, a senior scientist at the National Cancer Institutes in the US.

“This study of oral cancer complements existing studies of head and neck squamous cell carcinomas.”