EPIGENETICS PROJECT

PIYAPA TANTISIRIVAT PEAR

ADVANCED BIOLOGY
Mr. FILIPCZAK, ANDREW JAMES
 BACKGROUND INFORMATION

Do you wonder why identical twin has different personalities although they have all same
DNA and gene that makes up their bodies? According to cell biology and molecular, they should all
behave the same way and have exactly the same disease. Nevertheless, they are different. For
instance, one of a twin has bipolar disorder while other has a normal psychological condition. This is
the result of the epigenetic factor. Prefix epi- means outside or over. It basically means the same
thing.
Epigenetics is the study of changes in expression of a gene that does not involve a change in
genotype. This may come from age, environment, and lifestyle of people. Although this may seem to
be impossible to change our gene expression, they are believed to change the gene in at least three
ways which include histone modification in composing DNA, DNA methylation and noncoding in RNA.
Cancer is one of the things that I would like to choose in observing epigenetic. Cancer is when
the cell loses control in cell division, hence divide rapidly and invade the original cell that supposes to
be in there. Although our immune system can sometimes kill those cells, it does not thoroughly which
t it will divide and form massive of abnormal cells. This will result in tumor growing which can cause
pain or decrease function of that organ.
Doctor usually consults cancer by TNM staging system. T represents a size of the tumor that
we can indicate how far cancer is spread into the nearby cell. It is ranged from 1 to 4 which one is
small and four is large. N represents the spread id cancer to fluids system in the body. It will be
measured by lymph node of the body which is ranged from 0 to 4. Zero means that there is no cancer
cell in the lymph node while 3 means that there are a large amount of lymph that contains cancer cell
which basically means that cancer is spread widely throughout the body. M stands for metastasis
which means the spread of cancer to another part of the body. This has only two stages which are 0
and 1. Zero means they do not spread at all while one means cancer already spread to another part of
a body.
Cancer does not have to develop from that person only. It can be inherited from parents
through mutation of genes. Mutation of a gene is when there is a change in a gene that results in miss
or over nitrogenous base pair. This can result in positive, negative or no effect at all depend on the
environment that they live. There are many types of mutation that cause cancer. For instance, TP 53
is gene mutation which results in inability of controlling tumor growth which results in cell dividing

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so fast. Mutation of gene that causes cancer that I would like to observe is brac1 which can cause
breast cancer and ovarian cancer.
BRAC1 is the gene that provides the instruction in making protein that use to stop tumor growth. It
helps in maintaining the stabilities of gene in the cell which include the reparation of damage in DNA,
protein ubiquitination and the checkpoint to determine whether the activities inside cell are
appropriate or not. It also maintains stability of genome too. Mutation of BRAC 1 will result in small
version of gene BRAC1 or protein to copy one another. which result in deficiency of protein that uses
for tumor suppressor or DNA repairment. This deficiency will allow tumor to grow easier and
stimulates cell to divide rapidly. This will result in higher risk of getting breast cancer, ovarian
cancer, and prostate cancer. It also includes pancreatic cancer and colon cancer in the minor case too.
This can be shown in the statistic that woman who has BRAC1 has 60 percent in getting ovarian
cancer while normal woman has only about1.6 percent chance.
Mutation of gene BRAC1 is located on 17q21.31, which is the long (q) arm of chromosome 17 at
position 21.31 in cytogenetic location and it is one base pairs 43,044,295 to 43,125,483 on
chromosome 17.

It can be identified through genetic testing. Genetic testing is medical test where you test to
identify the mutation of gene in chromosome. This will give information if you have risk for genetic
disorder or how you are likely to pass on that gene to your daughter and son. There are various types
of test in genetic testing. For instance, molecular genetic studies only one specific gene that can lead
to genetic disorder. Chromosomal genetic is used to identify large genetic change like extra copies of
chromosome. Biochemical testing studies amount and activity of protein that regulates the DNA.

Genetic testing is recommended to test if you meet with either one of categories because it can
have both good and bad effects. It makes you acknowledge your likelihood of having disease while it
can affect you mental to feel bad and depress.

You have familys member or relative who has breast cancer before 50.

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 You have familys members that has breast cancer and ovarian cancer.
You have relative with triple-negative breast cancer.
You have familys member that has breast cancer and other types of cancer which can
be any types.
You have female in the families that both of her breasts has cancer.
You are Eastern Europe [Ashkenazi Jewish]
You are African American with breast cancer that is diagnosed before 35.
You have a male in your family that have breast cancer.
There is family member who is known to carry gene BRAC1.

If you test genetic testing and the result is positive, this means you have BRAC1 mutation.
Other than genetic testing, researchers found another thing that is different from other cancer

BRAC1 mutation are likely to be estrogen-receptor-negative which means that cancer

does not receive energy supplying by estrogen hormone and it is likely to be high-
grade cell growth. This makes us know that we should use chemotherapy to treat
patient rather than hormonal therapy which is anti-estrogen.
BRAC1 usually test negative for HER2. HER2 is the mutation that usually develop in
woman over time. Having too many receptors of these can trigger cell growth which
results in breast cancer. Moreover, cancer that develops from this mutation is usually
belligerent. However, it can be treated by using Trastuzumab which is chemical that
targets for HER2 receptors.
BRAC1 does not make woman have many tumors in the same breast when they
already have breast cancer.

Air pollution is one of the environmental concerns that we have. It is because now most of the
countries are industrialized and deforestation occurs in many places. This makes harmful and
dangerous substance enter into the atmosphere and makes it become dirtier which results in
difficulty in inhaling of organism including plant. This can be classified into two types which are
visible air pollution and invisible air pollution which are. For visible air pollution, it can be
combustion of fuels that release more carbon and including nitrogen oxide. Also, dust that is small
particle mixes into the air too. For invisible air pollution, it can be sulfur dioxide or methane.

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 Causes of this air pollution come from action of ourselves. First cause is from burning of fossil
fuels. This can come from industrial section that we burn coal and use petroleum to provide energy
source that we can use. Also, from the transportation, vehicle including plane release a large amount
of pollution into the air. Not only sulfur dioxide that has been released in each case, carbon monoxide
also has been released too. This can affect in reparatory system because carbon monoxide binds to
hemoglobin which lessens the amount of oxygen in body system. The second cause is from
agriculture activities. Methane can be released from animal that farmer raises to use them in working
or in making some products. Moreover, hazardous gas can be released through pesticide and
fertilizers too. The third one is mining operations. The dust from extracting mineral is so massive that
it can be dangerous for workers' health and areas nearby too. The last but not least is from our indoor
daily routine life.

My objective of this lab experiment is to observe if environment has an impact on risks of

getting cancer or not Cancer is known as anaerobic which means that it best survives in the condition
that has low rate of oxygen. It can quickly spread and fasten tumor progression. In this experiment, I
will observe both men and women who carry gene mutation BRAC1 in two different air pollution
conditions which are clean and polluted condition. This is to see how environment affects on people
who carry gene BRAC1. This will include different races too.

QUESTION

How has air pollution an impact on people who carry gene mutation BRAC1 on rate of getting cancer?

HYPOTHESIS

Exposure to air pollution has an impact on rate of getting cancer of people who carry gene
mutation BRAC1

PREDICTION

If air pollution has an impact on rate of getting cancer, then more people who carries gene
mutation BRAC1 will more likely to get cancer during their lifetime.

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 EXPERIMENT

In this experiment, I will get 1000 people who have gene mutation BRAC1 that is inherited
from their family which can be done by checking their families' history through pedigree or genetic
testing. They must not use mammogram to check or diagnose too. Moreover, the age of participants
must be around 40-50 years old. The table below will show a number of participants require from
each area to observe. Make sure that they are citizen from those areas, not migrants who move there.

Live in the clean environment Live in the polluted environment

Continent
Female Male Female Male
North America 50 50 50 50
South America 50 50 50 50
Europe 50 50 50 50
Africa 50 50 50 50
Asia & Oceania 50 50 50 50
Total number of
250 250 250 250
participants
** In this experiment, we combine Central America to North America**

To be more specific about how to distinguish clean environment and polluted environment, I
have set the number of polluted indexes. For the clean environment, air pollution index should be in
the range of 0 to 50 which environmental protection agencies defines this as good environment. For
the polluted air environment, it should be in range of 251 to 300 that environmental protection
agencies define as very unhealthy environment that can affect population to suffer from more serious
health diseases. To ensure that environment condition will maintain as it is, we have some
requirement for people in that area. For participant who lives in that area, they should not use
pollution protection product like mask to protect themselves from exposing to their environment.
They also should not use air filter in their house to reduce the amount of dust or anything that make
pollution index lessen than the range that I limit. For participant who lives in clean area, they should
not work in any jobs that make themselves expose to pollution over the range. For instance, they
should not work in construction site or work in the mining. They should work in the job that makes
them expose to air pollution in the average rate of city.

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 Continent Clean environment example Polluted environment example

North America Calgary, Canada Mexico city , Mexico

South America Santa Gertrudes, Brazil Peru

Europe Reykjavik, Iceland Brescia Villaggio Sereno,

Lombardia
Africa Mtunzini, RichardsBay Senegal

Asia & Oceania Danang, Vietnam Civic Center, Dazhou, China

When we get all participants ready, we will take cells sample and quantity of the DNA
methylation of people who carry mutation BRAC1. We also ultrasound their breast to follow up and
to first ensure that they show no sign of developing cancer since the beginning of experiment.
Moreover, we also test their blood to observe more about their health condition. The time that I
choose to conduct the experiment is ten years. So every year, I will take the sample of DNA and blood,
MRI and ultrasound to see how their progress and change. This also makes us know more about their
health condition and how many tumors that occur more in their bodies or how their tumors growth
are. Pet scan also requires for every two years to see if there are any parts of body that show sign of
developing cancer.

When we get all data, we will analyze data in three steps. The first step is to analyze
environment as a whole. We will divide the data into two group which are clean environment and
polluted environment. Then, we will compare those two data together to see if the environment has
an impact on rate getting cancer or not. In the second step, we will analyze data even deeper as if
environment affects each gender different or not. In this step, we will compare results of male and
female to see if there are differences between information and results that we get or not. The last but
no least step that we will choose to analyze impacts on environment in different races. In this step, we
will compare each race that lives the same air condition that I have set have different result at the
end. This is because each race has evolved to live in different areas so environmental effect might not
be the same in these races.

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 CONTROL

1. Age 40-50: The reason that I select this age group is because it is the period that most of
people who carry BRAC1 are diagnosed with cancer. Also, it is the time that they have the
highest percentage of developing new breast cancer in five years too. Moreover, risks of
developing ovarian cancer also increase during this certain period of life too.
2. Participant have to inherit this gene from their families: The reason that I choose this group of
participants is because we can determine how severe this mutation is in each particular family
in which allows us to choose the range that we want.
3. Participant must not use mammogram to check or diagnose: This is because mammogram
uses radiation that can affect cell cycle or DNA and other organelles which result in abnormal
function too. There are some research studies that found that if they have mammogram
before, the rate of diagnosing with breast cancer when they are 40 will increase from 9 to 14
percent too.
4. Equal number from different continents. Also, they have to be the citizen whose ancestors also
live in that area: This is because different races evolve to live in different environmental
conditions. As they evolve to live in different areas, the result that when they expose to similar
environmental conditions can be different. For the reason that have to ensure that every
participant has to have ancestor who live in that certain areas is to ensure that she will
inherited that gene that evolve to live in that particular environment.
5. An equal number of two different genders: As we know that two sexes and impact from
BRAC1 are different like the rate of men and women who have BRAC1 of getting breast cancer
are different we have to make sure that we keep these data equal so that the information from
each place will not be bias too.
6. The range of air pollution index: The reason that I choose the range of 0-50 to be clean
environment is because it has very low toxic rate that nobody who lives in that area will suffer
from air condition. On the other hand, the reason that I choose the range of 251-300 to be
polluted environment is because it is dangerous for their health but not too hazardous would
make everyone suffer serious diseases from certain environment.
7. Patients have to do MRI and ultrasound every year. Pet scan also requires for every two
years to see if there are any parts of body that show sign of developing cancer: The reason
that I use MRI and ultrasound to examine each participant every year is because it has

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 minimized effect of changing condition of tumor or normal tissue while allows us to observe
change in body as a whole. For pet-scan, it allows us to know if there are any parts of body
that show signs of developing cancer. This can be indicated by amount of glucose that that
particular tissue uses which will result in different intensity of light. However, pet-scan should
not be conducted every year as it uses radiation so I choose two years period instead of one.

IMPLICATION

Talking specifically about people who carry that gene BRAC1, this experiment will tell them
whether they should be aware of environmental condition that they live in or not. In case that
environmental condition especially air pollution has an impact on rate of getting cancer, they can at
least to cleaner environment to lessen their risks of getting cancer that is already high. Talking about
society as a whole, this can raise awareness of air pollution issue that has been increasing rapidly in
these days. By doing this experiment, it can show how air pollution can affect health. People who
carry gene mutation BRAC1 represent people in the society and how polluted environment can affect
them. It also shows clean environment can be benefit to people. This makes people in the society see
the idealistic model that they want to live and help each other to improve air condition to be as best
as they can.

BIBLIOGRAPHY

Air Quality Index. (2016, August 31). Retrieved December 03, 2016, from Airnow:
https://airnow.gov/index.cfm?action=aqibasics.aqi
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https://ghr.nlm.nih.gov/gene/BRCA1
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http://www.naturalhealth365.com/brca_gene.html/

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