LIFE09200604007 Tabish - Homi Bhabha National Institute

Discussion
DNA repair genes and MPN risk signature between the two groups (data not shown).
Although the difference between the G Score of MPN and control group was not huge a
significant difference between the G Score of patient and control samples in all the
three categories was observed with our earlier data set also, signifying the importance
of measuring G Score for MPN risk assessment. This emphasizes our present
observation and demonstrates that combination of risk alleles probably is a risk factor
with modest discriminatory ability between patient and control group.
G Score – phenotype correlation
Gene polymorphisms have long been associated with cancer risk; however the
real implication of these gene polymorphisms with increased cancer risk can only be
interpreted if they have any functional significance. This approach of understanding
effect of gene polymorphisms at functional level has been phenomenal and has been
applied to deduce the functional significance of genetic predisposition in cancer risk 49-
52, 201 .
Many such genotype-phenotype correlation studies have been conducted on
lung cancer. Comparable to our study, apoptotic capacity was found to be a risk factor
for lung cancer development and the risk was observed to be modulated by the Fas -
A 670 G polymorphism 51 . Similarly apoptosis, DNA repair and decreased G2/M cell
cycle check point function are found to be compromised in lung cancer with variations
in ATM, CDKN1A, BRCA2, ERCC6, TP53, and TP53BP1 genes 53, 201 . On the
contrary in another report XPA gene polymorphism, a DNA binding protein in the
nucleotide excision repair pathway, has been observed to modulate repair capacity and
associated with decreased lung cancer risk, especially in the presence of exposure to
tobacco carcinogens 52 .
Other than lung cancer, analogous reports are available for breast cancer
where polymorphisms in nucleotide excision repair genes and DNA repair capacity
phenotype has been associated with breast cancer risk 54, 55 . In another report by
Minard et al. evaluation of glutathione S-transferase polymorphisms and mutagen
sensitivity as risk factors for the development of second primary tumours in 303
patients previously diagnosed with early-stage head and neck cancer has been done 49 .
These studies demonstrate the functional significance of genetic variation in different
individuals and then their probable implication on various phenotypes and eventually
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