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Angiotensin-converting
enzyme (ACE) is involved in catalyzing the conversion of angiotensin I into a
physiologically active peptide angiotensin II. ACE inhibitors are widely used
as pharmaceutical drugs in the treatment of type 2 diabetes. However, angiotensin
II association with breast cancer among certain ethnic population has shown to
have possible mitogenic and angiogenic effects in human cell lines and animal
models of breast cancer. Research have been conducted on certain group of
population to study the hypothesis that reduced ACE activity is associated with
reduced risk of breast cancer. In these studies emphasis is given to investigate
the associations between gene polymorphisms, such as the study performed among
the Chinese women in Singapore to decipher the relation between the ACE A-240T
and insertion/deletion (I/D) gene polymorphisms and breast cancer risk
association41. It was found in this study that one or two
copies of low-risk A allele reduced the risk of breast cancer. The study
suggested that the renin-angiotensin system may serve as a therapeutic target
for breast cancer treatment and prevention. Moreover, it was also conveyed that
by excluding patient subjects with medical conditions such as diabetes the risk
reduction was enhanced. As we see, there is a clear association hinted from
this conclusion between the association of diabetes and breast cancer. Similar
study was conducted to assess the frequency of ACE I/D polymorphism in patients
with type 2 diabetes mellitus in the population of Brazil. In this particular
study, it was deduced that no association between the D allele and type 2
diabetes was found in the Brazilian population. The idea behind these
aforementioned performed researches was to find out the association between the
alleles (low-risk/high-risk) and the disease risk. Clearly, since the data
suggests that an integrative study between breast cancer and diabetes has not
been covered in recent researches to have a holistic understanding of the
influence of ACE gene in these diseases, we need to perform an association
study, where in our case we will be focussing on the population of Qatar. In
our research, we will not be limited to variant or polymorphism calling by NGS
analysis for the identification of risk-alleles but, we will also focus on modeling
these mutant alleles at macromolecular level to study protein-drug binding
affinity; this will help to conclude the importance of the drugs to be used to
combat these deleterious diseases by targeting them simultaneously.