Arsenic the directly related family members will also be

Arsenic
is a heavy metal associated with increased risk for development of skin and
lung cancer after chronic exposure. It is ubiquitous in the environment; it can
be found in water, air, and food. Despite of the permissible levels for arsenic
in drinking water at 10ppb, there are many countries that are under-regulated
by their government, suffering from different types of cancer from drinking
arsenic-contaminated water. My current research is focused on the effect of
chronic exposure to low levels of arsenic on carcinogenesis. 

Toxicological
responses of arsenic, such as cancer development, from chronic exposure to low
levels of arsenic differ among people. Cancer is highly associated with an intricate
interplay between genetic and environmental factors. To identify sequence
variants that contribute to increased likelihood of developing cancer, we can
collect DNA samples from individuals with different background, such as
smoking, family history, and country of origin (along with arsenic content in
drinking water of corresponding countries), and perform RNA-seq. I would make
sure that I have at least a pair of individuals (normal and patients) for each
condition, to compare the results. RNA-seq is an unbiased approach, unlike
probe-based approach, such as ChIP and Mass Spec. Using the data, we can
compare with the reference sequence and analyze for variants, such as SNPs,
In/Dels, and structural rearrangements. I would focus on patients, who do not
have any smoking history, or family history of cancer, and compare with the
normal individuals from the same geographical regions, and the same background.
By comparing those two individuals, we would be able to identify genetic factor
that contributes to increased likelihood of developing cancer from chronic
exposure to low levels of arsenic. To rule out the possibility of heritable
factors, DNA of the directly related family members will also be collected. To
detect the expression of each allele, we will increase the coverage. By
identifying genes that are susceptible to arsenic toxicity to even low levels,
this study can reinforce the regulation of the permissible levels of arsenic in
drinking water. This study will not only identify the genes that are
susceptible, but also identify genes that are resistant to arsenic. Furthermore,
this study can predict early onset of cancer development in individuals.

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