LIFE09200604007 Tabish - Homi Bhabha National Institute
LIFE09200604007 Tabish - Homi Bhabha National Institute
LIFE09200604007 Tabish - Homi Bhabha National Institute
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Review of Literature<br />
2.6 Genotype phenotype correlation studies<br />
Since last few decades a number of studies have reported association of gene<br />
polymorphisms with cancer risk. However the real implication of these gene<br />
polymorphisms with increased cancer risk can only be interpreted if they have any<br />
functional significance. Therefore undertaking genotype-phenotype correlation studies<br />
is extremely important to understand the functional significance of the gene<br />
polymorphisms. Numerous studies have been conducted during last one decade to<br />
evaluate the functional significance of gene polymorphisms in normal individuals 46-48 .<br />
This approach of understanding effect of gene polymorphisms at functional level has<br />
been phenomenal and has been applied to deduce the functional significance of genetic<br />
predisposition in cancer risk 49-52 .<br />
One of such reports describes alteration in the apoptotic capacity to be a risk<br />
factor for lung cancer development and the risk was observed to be modulated by the<br />
Fas -A 670 G polymorphism 51 . Similarly, variations in p53 gene have been associated<br />
with apoptosis and DNA repair and in turn with lung cancer risk 53 . On the contrary<br />
XPA gene polymorphism, a DNA binding protein in the nucleotide excision repair<br />
pathway, has been observed to modulate repair capacity and is associated with<br />
decreased lung cancer risk, especially in the presence of exposure to tobacco<br />
carcinogens 52 . Other than lung cancer, analogous reports are available for breast cancer<br />
also where polymorphisms in nucleotide excision repair genes and DNA repair capacity<br />
phenotype has been with breast cancer risk 54, 55 . In another report by Minard et al.<br />
evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk<br />
factors for the development of second primary tumours in 303 patients previously<br />
diagnosed with early-stage head and neck cancer has been done 49 . These studies<br />
demonstrate the functional significance of genetic variation in different individuals and<br />
then their probable implication on various phenotypes and eventually cancer risk, hence<br />
emphasizing the importance of undertaking genotype-phenotype correlation studies in<br />
understanding UADT MPN pathogenesis.<br />
2.7 Model system: Epstein Barr virus transformed lymphoblastoid cell lines<br />
In order to understand the etiology of UADT MPN there is a need to undertake<br />
genotype phenotype correlation studies. However, one of the prime requisites for<br />
performing long term genotype-phenotype correlation studies is the continuous supply<br />
of starting parent material. This can be overcome to some extent by establishing<br />
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