FMS 1 - Week 6 Tutorial 1 LO

All about breast cancer

Breast cancer overview

Cancer occurs when changes called mutations take place in genes that regulate cell
growth. The mutations let the cells divide and multiply in an uncontrolled, chaotic way.
The cells keep multiplying, producing copies that get progressively more abnormal. In
most cases, the cell copies eventually form a tumor.

Breast cancer is cancer that develops in breast cells. Typically, the cancer forms in
either the lobules or the ducts of the breast. Lobules are the glands that produce milk,
and ducts are the pathways that bring the milk from the glands to the nipple. Cancer
can also occur in the fatty tissue or the fibrous connective tissue within your breast.

The uncontrolled cancer cells often invade other healthy breast tissue and can travel to
the lymph nodes under the arms. The lymph nodes are a primary pathway that helps
the cancer cells move to other parts of the body. See pictures and learn more about
the structure of the breast.

How common is breast cancer?

According to the Centers for Disease Control and Prevention (CDC), breast cancer is
the most common cancer in women. And according to statistics from the American
Cancer Society (ACS), nearly 232,000 new cases of invasive breast cancer were
expected to be diagnosed in the United States in 2015. Invasive breast cancer is cancer
that has spread from the ducts or glands to other parts of the breast. More than 40,000
women were expected to die from the disease.

Breast cancer can also be diagnosed in men. The ACS also estimated that in 2015,
more than 2,000 men would be diagnosed, and more than 400 men would die from
the disease. Find out more about breast cancer numbers around the world.

Types of breast cancer

There are several types of breast cancer, which are broken into two main categories:
“invasive” (as mentioned above), and “noninvasive,” or in situ. While invasive cancer
has spread from the breast ducts or glands to other parts of the breast, noninvasive
cancer has not spread from the original tissue.

These two categories are used to describe the most common types of breast cancer,
which include:
Ductal carcinoma in situ. Ductal carcinoma in situ (DCIS) is a noninvasive condition.
With DCIS, the cells that line the ducts in your breast change and look cancerous.
However, DCIS cells haven’t invaded the surrounding breast tissue.

Lobular carcinoma in situ. Lobular carcinoma in situ (LCIS) is cancer that grows in the
milk-producing glands of your breast. Like DCIS, the cancer cells haven’t yet invaded
the surrounding tissue.

Invasive ductal carcinoma. Invasive ductal carcinoma (IDC) is the most common type
of breast cancer. This type of breast cancer begins in your breast’s milk ducts and then
invades nearby tissue in the breast. Once the breast cancer has spread to the tissue
outside your milk ducts, it can begin to spread to other nearby organs and tissue.

Invasive lobular carcinoma. Invasive lobular carcinoma (ILC) first develops in your

breast’s lobules. If breast cancer is diagnosed as ILC, it has already spread to nearby
tissue and organs.

Other, less common types of breast cancer include:

Paget disease of the nipple. This type of breast cancer begins in the breasts’ ducts,
but as it grows, it begins to affect the skin and areola of the nipple.

Phyllodes tumor. This very rare type of breast cancer grows in the connective tissue of
the breast.

Angiosarcoma. This is cancer that grows on the blood vessels or lymph vessels in the
breast.

The type of cancer you have determines your treatment options, as well as your
prognosis (likely long-term outcome). Learn more about types of breast cancer.

Inflammatory breast cancer

Inflammatory breast cancer (IBC) is a rare but aggressive type of breast cancer. IBC
makes up only between 1 and 5 percent of all breast cancer cases.

With this condition, cells block the lymph nodes near the breasts, so the lymph vessels
in the breast can’t properly drain. Instead of creating a tumor, IBC causes your breast to
swell, look red, and feel very warm. A cancerous breast may appear pitted and thick,
like an orange peel.

IBC can be very aggressive and progress quickly. For this reason, it’s important to call
your doctor right away if you notice any symptoms. Find out more about IBC and the
symptoms it can cause.
Triple-negative breast cancer
Triple-negative breast cancer is another rare disease type, affecting only about 10 to 20
percent of people with breast cancer. To be diagnosed as triple-negative breast cancer,
a tumor must have all three of the following characteristics:

It lacks estrogen receptors. These receptors are cells that bind, or attach, to the
hormone estrogen. If a tumor has estrogen receptors, it needs estrogen to grow.

It lacks progesterone receptors. These receptors are cells that bind to the hormone
progesterone. If a tumor has progesterone receptors, it needs progesterone to grow.

It doesn’t have additional HER2 proteins on its surface. HER2 is a protein that fuels
breast cancer growth.

If a tumor meets these three criteria, it’s labeled a triple-negative breast cancer. This
type of breast cancer has a tendency to grow and spread more quickly than other types
of breast cancer.

Triple-negative breast cancers are difficult to treat because traditional breast cancer
treatments are not effective. Learn about treatments for triple-negative breast cancer,
as well as survival rates.

Risk factors for breast cancer

There are several risk factors that increase your chances of getting breast cancer.
However, having any of these doesn’t mean you will definitely develop the disease.

Some risk factors can’t be avoided, such as family history. Other risk factors, such as
smoking, you can change. Risk factors for breast cancer include:

Age. Your risk for developing breast cancer increases as you age. Most invasive breast
cancers are found in women over age 55.

Drinking alcohol. Drinking excessive amounts of alcohol raises your risk.

Having dense breast tissue. Dense breast tissue makes mammograms hard to read. It
also increases your risk of breast cancer.

Gender. Women are 100 times more likely to develop breast cancer than men.

Genes. Women who have the BRCA1 and BRCA2 gene mutations are more likely to
develop breast cancer than women who don’t. Other gene mutations may also affect
your risk.
Early menstruation. If you had your first period before age 12, you have an increased
risk for breast cancer.

Giving birth at an older age. Women who don’t have their first child until after age 35
have an increased risk of breast cancer.

Hormone therapy. Women who took or are taking postmenopausal estrogen and

progesterone medications to reduce their signs of menopause symptoms have a higher
risk of breast cancer.

Inherited risk. If a close female relative has had breast cancer, you have an increased
risk for developing it. This includes your mother, grandmother, sister, or daughter. If you
don’t have a family history of breast cancer, you can still develop breast cancer. In fact,
the majority of women who develop it have no family history of the disease.

Late menopause start. Women who do not start menopause until after age 55 are
more likely to develop breast cancer.

Never being pregnant. Women who never became pregnant or never carried a

pregnancy to full-term are more likely to develop breast cancer.

Previous breast cancer. If you have had breast cancer in one breast, you have an
increased risk of developing breast cancer in your other breast or in a different area of
the previously affected breast.

Breast cancer symptoms

In its early stages, breast cancer may not cause any symptoms. In many cases, a tumor
may be too small to be felt, but an abnormality can still be seen on a mammogram. If a
tumor can be felt, the first sign is usually a new lump in the breast that was not there
before. However, not all lumps are cancer.

Each type of breast cancer can cause a variety of symptoms. Many of these symptoms
are similar, but some can be different. Symptoms for the most common breast cancers
include:

a breast lump or tissue thickening that feels different than surrounding tissue and has
developed recently

breast pain

red, pitted skin over your entire breast

swelling in all or part of your breast

a nipple discharge other than breast milk

bloody discharge from your nipple

peeling, scaling, or flaking of skin on your nipple or breast

a sudden, unexplained change in the shape or size of your breast

inverted nipple

changes to the appearance of the skin on your breasts

a lump or swelling under your arm

If you have any of these symptoms, it doesn’t necessarily mean you have breast cancer.
For instance, pain in your breast or a breast lump can be caused by a breast cyst. Still,
if you find a lump in your breast or have other symptoms, you should see your doctor
for further examination and testing. Learn more about possible symptoms of breast
cancer.

Diagnosis of breast cancer

To determine if your symptoms are caused by breast cancer or a benign breast
condition, your doctor will do a thorough physical exam in addition to a breast exam.
They may also request one or more diagnostic tests to help understand what’s causing
your symptoms.

Tests that can help diagnose breast cancer include:

Mammogram. Perhaps the best way to see below the surface of your breast is with an
imaging test called a mammogram. Many women get annual mammograms to check
for breast cancer. If your doctor suspects you may have a tumor or suspicious spot, they
will also request a mammogram. If an abnormal area is seen on your mammogram,
your doctor may request additional tests.

Ultrasound. A breast ultrasound creates a picture of the tissues deep in your breast.

The ultrasound uses sound waves to do this. An ultrasound can help your doctor
distinguish between a solid mass, such as a tumor, and a benign cyst.

Your doctor may also suggest tests such as an MRI or a breast biopsy. Learn about
other tests that can be used to detect breast cancer.

Breast biopsy
If your doctor suspects breast cancer, they may order both a mammogram and an
ultrasound. If both of these tests can’t tell your doctor if you have cancer, your doctor
may do a test called a breast biopsy.

During this test, your doctor will remove a tissue sample from the suspicious area to
have it tested. There are several types of breast biopsies. With some of these tests,
your doctor uses a needle to take the tissue sample. With others, they make an incision
in your breast and then remove the sample.
Your doctor will send the tissue sample to a laboratory. If the sample tests positive for
cancer, the lab can test it further to tell your doctor what type of cancer you
have. Learn more about breast biopsies, how to prepare for one, and what to expect.

Breast cancer stages

Breast cancer can be divided into stages based on how severe it is. Cancers that have
grown and invaded nearby tissues and organs are at a higher stage than cancers that
are still contained to the breast. In order to stage a breast cancer, doctors need to
know:

if the cancer is invasive or noninvasive

how large the tumor is

whether the lymph nodes are involved

if the cancer has spread to nearby tissue or organs

Breast cancer has five main stages: stages 0–5.

Stage 0 breast cancer

Stage 0 is DCIS. Cancer cells in DCIS remain confined to the ducts in the breast and
have not spread into nearby tissue.

Stage 1 breast cancer

There are two types of stage 1 breast cancer:

Stage 1A: The primary tumor is 2 centimeters wide or less and the lymph nodes are
not affected.

Stage 1B: Cancer is found in nearby lymph nodes, and either there is no tumor in the
breast, or the tumor is smaller than 2 centimeters.

Stage 2 breast cancer

Stage 2 breast cancers are also divided into two categories:

Stage 2A: The tumor is smaller than 2 centimeters and has spread to 1–3 nearby
lymph nodes, or it’s between 2 and 5 centimeters and hasn’t spread to any lymph
nodes.
Stage 2B: The tumor is between 2 and 5 centimeters and has spread to 1–3 axillary
(armpit) lymph nodes, or it’s larger than 5 centimeters and hasn’t spread to any lymph
nodes.

Stage 3 breast cancer

There are three main types of stage 3 breast cancer.

Stage 3A: This stage can have several types of cancer:

The cancer has spread to 4–9 axillary lymph nodes or has enlarged the internal
mammary lymph nodes, and the primary tumor can be any size.

The tumor is bigger than 5 centimeters and small groups of cancer cells are found
in the lymph nodes.

Tumors are greater than 5 centimeters and the cancer has spread to 1–3 axillary
lymph nodes or any breastbone nodes.

Stage 3B: A tumor has invaded the chest wall or skin and may or may not have
invaded up to 9 lymph nodes.

Stage 3C: Cancer is found in 10 or more axillary lymph nodes, lymph nodes near
the collarbone, or internal mammary nodes.

Stage 4 breast cancer

Stage 4 breast cancer can have a tumor of any size, and its cancer cells have spread to
nearby and distant lymph nodes, as well as distant organs.

The testing your doctor does will determine the stage of your breast cancer, which will
affect your treatment. Find out how different breast cancer stages are treated.

Metastatic breast cancer

Metastatic breast cancer is another name for stage 4 breast cancer. It’s breast cancer
that has spread from your breast to other parts of your body, such as your bones, lungs,
or liver.

This is the most serious type of breast cancer, and it requires immediate treatment.
Your oncologist (cancer doctor) will create a treatment plan with the goal of stopping
the growth and spread of the tumor, or tumors. Learn about treatment options for
metastatic cancer, as well as factors that affect your outlook.

Breast cancer treatment

Your breast cancer’s stage, how far it has invaded (if it has), and how big the tumor has
grown all play a large part in determining what kind of treatment you’ll need.

To start, your doctor will determine your cancer’s size, stage, and grade (how likely it is
to grow and spread). After that, the two of you can discuss your treatment options.
Surgery is the most common treatment for breast cancer. In addition to surgery, most
women have a complementary treatment, such as chemotherapy, radiation, or
hormone therapy.

Surgery

Several types of surgery may be used to remove breast cancer, including:

Lumpectomy. This procedure removes only the suspicious or cancerous spot, leaving

most surrounding tissue in place.

Mastectomy. In this procedure, a surgeon removes an entire breast. In a double

mastectomy, both breasts are removed.

Sentinel node biopsy. This surgery removes some of the lymph nodes that receive
drainage from the tumor. These lymph nodes will be tested. If they don’t have cancer,
you may not need additional lymph-removing surgery.

Axillary lymph node dissection. If lymph nodes removed during a sentinel node
biopsy test positive, your doctor may perform this procedure to remove additional
lymph nodes.

Contralateral prophylactic mastectomy. Even though breast cancer may be present in

only one breast, some women elect to have a contralateral prophylactic mastectomy.
This surgery removes your healthy breast to reduce your risk of developing breast
cancer again.

Radiation therapy

With radiation therapy, high-powered beams of radiation are used to target and kill
cancer cells. Most radiation treatments use external beam radiation. This technique
uses a large machine on the outside of the body.

Advances in cancer treatment have also enabled doctors to irradiate cancer from inside
the body. This type of radiation treatment is called brachytherapy. To conduct
brachytherapy, surgeons place radioactive seeds, or pellets, inside the body near the
tumor site. The seeds stay there for a short period of time and work to reduce cancer
cells.
Chemotherapy

Chemotherapy is a drug treatment used to destroy cancer cells. Some people may
undergo chemotherapy on its own, but this type of treatment is often used along with
other treatments, especially surgery.

In some cases, doctors prefer to give patients chemotherapy before surgery. The hope
is that the treatment will shrink the tumor, and then the surgery will not need to be as
invasive. Chemotherapy has many unwanted side effects, so discuss your concerns with
your doctor before starting treatment.

Hormone therapy

If your type of breast cancer is sensitive to hormones, your doctor may start you
on hormone therapy. Estrogen and progesterone, two female hormones, can stimulate
the growth of breast cancer tumors. Hormone therapy works by blocking your body’s
production of these hormones. This action can help slow and possibly stop the growth
of your cancer.

Medications

Certain medications are designed to attack specific abnormalities or mutations within

cancer cells. For example, Herceptin (trastuzumab) can block your body’s production of
the HER2 protein. HER2 helps breast cancer cells grow, so taking a medication to slow
the production of this protein may help slow cancer growth.

Your doctor will tell you more about any specific treatment they recommend for
you. Learn more about breast cancer treatments, as well as how hormones affect
cancer growth.

Breast cancer prevention

Breast cancer doesn’t have an identifiable cause. For that reason, it can’t be prevented
entirely. However, following a healthy lifestyle, getting regular screening, and taking
any preventive measures your doctor recommends can help reduce your risk.

Lifestyle factors

Lifestyle factors can affect your risk of breast cancer. For instance, women who
are obese have a higher risk of developing breast cancer. Maintaining a healthy diet
and getting more exercise could help you lose weight and lower your risk.
Drinking too much alcohol also increases your risk. This is true of having two or more
drinks per day, and of binge drinking. However, a recent study found that even one
drink per day increases your risk of breast cancer. If you drink alcohol, talk to your
doctor about what amount they recommend for you.

Breast cancer screening

Having regular mammograms may not prevent breast cancer, but it can help reduce
the odds that it will go undetected. The American Cancer Society provides the
following general recommendations for mammograms:

Women ages 40 to 44: An annual mammogram is optional.

Women age 45 to 54: An annual mammogram is recommended.

Women 55 and older: A mammogram every 1 or 2 years is recommended, for as long

as you’re in good health and expected to live 10 more years or longer.

These are only guidelines. Specific recommendations for mammograms are different
for each woman, so talk with your doctor to see if you should get regular
mammograms.

Pre-emptive treatment

Some women are at increased risk of breast cancer due to hereditary factors. For
instance, if your mother or father has a harmful BRCA1 or BRCA2 gene mutation,
you’re at higher risk of having it as well. This significantly raises your risk of breast
cancer.

If you’re at risk for this mutation, talk to your doctor about your diagnostic and
treatment options. You may want to be tested to find out if you definitely have the
mutation. And if you learn that you do have it, discuss with your doctor any pre-
emptive steps you can take to reduce your risk of getting breast cancer. These steps
could include a prophylactic mastectomy(surgical removal of a breast).

Desc. The concepts of proto-oncogenes, oncogenes and surveillance

Mutations in proto-oncogenes are typically dominant in nature, and the
mutated version of a proto-oncogene is called an oncogene. Often, proto-
oncogenes encode proteins that function to stimulate cell division, inhibit cell
differentiation, and halt cell death.
All of these processes are important for normal human development and for the
maintenance of tissues and organs. Oncogenes, however, typically exhibit increased
production of these proteins, thus leading to increased cell division, decreased cell
differentiation, and inhibition of cell death; taken together, these phenotypes define
cancer cells. Thus, oncogenes are currently a major molecular target for anti-
cancer drug design.

From Good to Bad: How Proto-Oncogenes Become Oncogenes

Today, more than 40 different human proto-oncogenes are known. But what types of
mutations convert these proto-oncogenes into oncogenes? The answer is simple:
Oncogenes arise as a result of mutations that increase the expression level or activity of
a proto-oncogene. Underlying genetic mechanisms associated with oncogene
activation include the following: 

Point mutations, deletions, or insertions that lead to a hyperactive gene product 

Point mutations, deletions, or insertions in the promoter region of a proto-oncogene
that lead to increased transcription
Gene amplification events leading to extra chromosomal copies of a proto-oncogene
Chromosomal translocation events that relocate a proto-oncogene to a new
chromosomal site that leads to higher expression
Chromosomal translocations that lead to a fusion between a proto-oncogene and a
second gene, which produces a fusion protein with oncogenic activity

Targeting Oncogene Addiction to Treat Cancer

" "

2. How Carcinogens influence cell growth

The genetic material in the cell makes sure everything goes the way it's
supposed to in regards to controlling cell growth, division and life span. However,
when carcinogens are introduced in the body they can affect the genes and cause
them to change in a bad way. Theses mutations occur when the DNA makes a copy of
itself before mitosis. Therefore, the new cell that has been replicated also has a
mutation in its DNA. A cancer cell is born. Cancer cells don’t get the right message
from genes to stop growing or die and therefore they grow uncontrollably and divide
too often.
 Cancer cells can live forever. In normal cells the ends of the chromosomes
become shorter whenever the cell divides. The cell dies when the chromosomes are
worn down. Cancer cells retain their long chromosomes by continually adding bits back
on. This is what allows the cancer cells to live forever. They continue to reproduce and
grow forming lumps called tumors. The tumors can damage the tissue that surrounds
it. Sometimes cancer cells from the tumor break off and are carried by the blood
stream to other parts of the body. That is how the cancer spreads which means it has
metastasized.
That said, carcinogens like asbestos or UV rays, these external factors Varmus
describes above, do make DNA mutations—and thus cancer—more likely to occur.
They can give rise to cancers essentially in one of three ways: they can, like UV rays or
radiation, directly cause genetic mutations or they can cause cells to divide much more
rapidly, amplifying the normal rate of error inherent to cell division

3. What’s wrong with cancer cells?

Cancer cells behave differently than normal cells in the body. Many of these differences
are related to cell division behavior.

For example, cancer cells can multiply in culture (outside of the body in a dish) without
any growth factors, or growth-stimulating protein signals, being added. This is different
from normal cells, which need growth factors to grow in culture.

Cancer cells may make their own growth factors, have growth factor pathways that are
stuck in the "on" position, or, in the context of the body, even trick neighboring cells
into producing growth factors to sustain them^11start superscript, 1, end superscript.

"

Diagram showing different responses of normal and cancer cells to growth factor
presence or absence.

Normal cells in a culture dish will not divide without the addition of growth factors.
Cancer cells in a culture dish will divide whether growth factors are provided or not.
Cancer cells also ignore signals that should cause them to stop dividing. For instance,
when normal cells grown in a dish are crowded by neighbors on all sides, they will no
longer divide. Cancer cells, in contrast, keep dividing and pile on top of each other in
lumpy layers.
The environment in a dish is different from the environment in the human body, but
scientists think that the loss of contact inhibition in plate-grown cancer cells reflects
the loss of a mechanism that normally maintains tissue balance in the body^22start
superscript, 2, end superscript.

Another hallmark of cancer cells is their "replicative immortality," a fancy term for the
fact that they can divide many more times than a normal cell of the body. In general,
human cells can go through only about 40-60 rounds of division before they lose the
capacity to divide, "grow old," and eventually die^33start superscript, 3, end
superscript.

Cancer cells can divide many more times than this, largely because they express an
enzyme called telomerase, which reverses the wearing down of chromosome ends that
normally happens during each cell division^44start superscript, 4, end superscript.

Cancer cells are also different from normal cells in other ways that aren’t directly cell
cycle-related. These differences help them grow, divide, and form tumors. For instance,
cancer cells gain the ability to migrate to other parts of the body, a process
called metastasis, and to promote growth of new blood vessels, a process
called angiogenesis (which gives tumor cells a source of oxygen and nutrients). Cancer
cells also fail to undergo programmed cell death, or apoptosis, under conditions when
normal cells would (e.g., due to DNA damage). In addition, emerging research shows
that cancer cells may undergo metabolic changes that support increased cell growth
and division^55start superscript, 5, end superscript.

"
Diagram showing different responses of normal and cancer cells to conditions that
would typically trigger apoptosis.

A normal cell with unfixable DNA damaged will undergo apoptosis.

A cancer cell with unfixable DNA damage will not undergo apoptosis and will instead
continue dividing.

4. List various carcinogens and describe how they influence cell growth

Cancer is any disease in which normal cells are damaged and do not
undergo programmed cell death as fast as they divide via mitosis. Carcinogens may
increase the risk of cancer by altering cellular metabolism or damaging DNA directly
in cells, which interferes with biologicalprocesses, and induces the uncontrolled,
malignant division, ultimately leading to the formation of tumors. Usually, severe DNA
damage leads to programmed cell death, but if the programmed cell death pathway is
damaged, then the cell cannot prevent itself from becoming a cancer cell.
There are many natural carcinogens. Aflatoxin B1, which is produced by
the fungus Aspergillus flavus growing on stored grains, nuts and peanut butter, is an
example of a potent, naturally occurring microbial carcinogen. Certain viruses such
as hepatitis B and human papilloma virushave been found to cause cancer in humans.
The first one shown to cause cancer in animals is Rous sarcoma virus, discovered in
1910 by Peyton Rous. Other infectious organisms which cause cancer in humans
include some bacteria (e.g. Helicobacter pylori [2][3]) and helminths(e.g. Opisthorchis
viverrini [4] and Clonorchis sinensis [5].
Dioxins and dioxin-like compounds, benzene, kepone, EDB, and asbestos have
all been classified as carcinogenic.[6] As far back as the 1930s, Industrial smoke
and tobacco smoke were identified as sources of dozens of carcinogens,
including benzo[a]pyrene, tobacco-specific nitrosamines such as nitrosonornicotine,
and reactive aldehydes such as formaldehyde, which is also a hazard in embalming and
making plastics. Vinyl chloride, from which PVC is manufactured, is a carcinogen and
thus a hazard in PVC production.
After the carcinogen enters the body, the body makes an attempt to eliminate it
through a process called biotransformation. The purpose of these reactions is to make
the carcinogen more water-soluble so that it can be removed from the body. However,
in some cases, these reactions can also convert a less toxic carcinogen into a more
toxic carcinogen.

Associated cancer sites

Carcinogen Occupational uses or sources
or types
 • Smelting byproduct
• Component of:
• Alloys
• Electrical
• Lung and semiconductordevices
Arsenic and its • Skin • Medications (e.g. melarsoprol)
compounds
• Hemangiosarcoma • Herbicides
• Fungicides
• Animal dips
• Drinking water from
contaminated aquifers.

Not in widespread use, but found in:

• Constructions
• Lungs • Roofing papers
• Asbestosis • Floor tiles
• Gastrointestinal tract Fire-resistant textiles
Asbestos •
• PleuralMesothelioma • Friction linings (brake pads) (only
• Peritoneal outside Europe)
Mesothelioma • Replacement friction linings for
automobiles still may contain
asbestos

• Light fuel oil
• Former use as solvent and fumigant
• Printing
• Lithography
• Leukemia • Paint
Benzene
• Hodgkin's lymphoma • Rubber
• Dry cleaning
• Adhesives
• Coatings
• Detergents

• Missile fuel

Beryllium and its • Lightweight alloys

• Lung
compounds • Aerospace applications
• Nuclear reactors
 • Yellow pigments
• Phosphors
Cadmium and its
• Prostate • Solders
compounds[27]
• Batteries
• Metal paintings and coatings

• Paints
Hexavalent chromium(VI)
• Lung • Pigments
compounds
• Preservatives

• Lung[28]
IC engine exhaust gas • Exhaust gas from engines
• Bladder[28]

• Ripening agent for fruits and nuts

• Rocket propellant
Ethylene oxide • Leukemia
• Fumigant for foodstuffs and textiles
• Sterilant for hospital equipment

• Nickel plating
• Ferrous alloys
• Nose
Nickel • Ceramics
• Lung
• Batteries
• Stainless-steel welding byproduct

• Uranium decay
Radon and its decay • Quarries and mines
• Lung
products • Cellars and poorly ventilated
places

• Refrigerant
• Hemangiosarcoma • Production of polyvinyl chloride
Vinyl chloride
• Liver • Adhesive for plastics
• Former use in pressurized containers

Shift work that involves

• Breast
circadian disruption[29]

Involuntary smoking
• Lung
(Passive smoking)[30]
Radium-226, Radium-224,

Plutonium-238, Plutoniu • Bone (they are bone
m-239[31]
 • Nuclear fuel processing
seekers)
and other alpha particle
 • Radium dial manufacturing
emitters with high atomic
• Liver
weight

5. desc. How changes in DNA and RNA result in uncontrolled cellular growth
Cells have many different mechanisms to restrict cell division, repair DNA
damage, and prevent the development of cancer. Because of this, it’s thought that
cancer develops in a multi-step process, in which multiple mechanisms must fail before
a critical mass is reached and cells become cancerous. Specifically, most cancers arise
as cells acquire a series of mutations (changes in DNA) that make them divide more
quickly, escape internal and external controls on division, and avoid programmed cell
death

For instance, a protein that halts cell cycle

progression in response to DNA damage may
no longer sense damage or trigger a response.
Genes that normally block cell cycle
progression are known as tumor suppressors.
Tumor suppressors prevent the formation of
cancerous tumors when they are working
correctly, and tumors may form when they
mutate so they no longer work.

One of the most important tumor suppressors

is tumor protein p53, which plays a key role in
the cellular response to DNA damage. p53 acts primarily at the G11start subscript, 1,
end subscript checkpoint (controlling the G11start subscript, 1, end subscript to S
transition), where it blocks cell cycle progression in response to damaged DNA and
other unfavorable conditions1313start superscript, 13, end superscript.
When a cell’s DNA is damaged, a sensor protein activates p53, which halts the cell
cycle at the G11start subscript, 1, end subscript checkpoint by triggering production of
a cell-cycle inhibitor. This pause buys time for DNA repair, which also depends on p53,
whose second job is to activate DNA repair enzymes. If the damage is fixed, p53 will
release the cell, allowing it to continue through the cell cycle. If the damage is not
fixable, p53 will play its third and final role: triggering apoptosis (programmed cell
death) so that damaged DNA is not passed on.