LIFE09200604007 Tabish - Homi Bhabha National Institute
LIFE09200604007 Tabish - Homi Bhabha National Institute
LIFE09200604007 Tabish - Homi Bhabha National Institute
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Introduction<br />
1.1 Introduction<br />
Cancer has been rightfully crowned the „Emperor of all Maladies‟ owing to its<br />
increasing incidence, diverse forms and ability to affect various organs across different<br />
age groups. Even worse is its intractability to treatment and its irrepressible property to<br />
recur. With such dynamic efficacies this sovereign has evaded human understanding<br />
despite decades of research and ample funds being invested. This explains why cancer<br />
continues to be one of the principal causes of deaths worldwide and also in India, where<br />
it accounts for approximately 6% of total human deaths 1, 2 .<br />
One of the major cancers prevalent in the country is tobacco-related, Head and<br />
Neck Squamous Cell Carcinoma (HNSCC), of which, squamous cell carcinoma of<br />
Upper Aero-Digestive Tract (UADT) is the commonest cancer amongst Indian men 2, 3 .<br />
Early detection and advancement in diagnostic and treatment modalities has lead to<br />
improved disease management and increased survival of patients. However this<br />
improvement has not been able to mitigate the development of second/multiple primary<br />
neoplasm(s) (MPN) which now looms large as one of the major threats in early stage<br />
UADT cancer survivors 4-6 .<br />
In recent past increasing number of MPN cases in UADT cancers has become<br />
an important therapeutic concern. Survivors of early stage HNSCC have a 10-30% risk<br />
of developing second primary tumour in the same or distant region which is one of the<br />
prime reasons of increased morbidity and mortality 7, 8 . The most important risk factors<br />
for developing such cancers are tobacco habit and alcohol consumption, which have a<br />
synergistic effect. These genotoxic agents act by disrupting the genomic integrity<br />
leading to malignant transformation and subsequent cancer development. However it is<br />
well established that there is a considerable difference between individuals at the<br />
genetic level that affect their response to genotoxic insult and thus susceptibility to<br />
cancer, which is reflected by the fact that not all individuals exposed to similar type and<br />
dose of carcinogen develop cancer. There is a possibility of a different host<br />
environment interaction in individuals who develop UADT MPN. This difference could<br />
arise due to genetic variations in genes that are involved in carcinogen detoxification,<br />
repair of damaged DNA, cell cycle and cell death regulation and thereby, their ability to<br />
handle carcinogens. Convincing evidence from case-control studies analyzing<br />
cumulative polymorphisms suggests aberrant gene-environment interactions to be an<br />
important etiological factor in the genesis of MPN 7, 9-11 .<br />
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