Humongous Insurance

Genetics of Cancer

Presented by Gina Reyes, Amie Fitzwater, Brittany Anders-Larson, &

Yoshie Tamura

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Chapter Contents

• Cancer is Genetic, But Usually Not Inherited.

• Characteristics of Cancer• Origins of Cancer Cells• Cancer Genes• A Series of Genetic Changes Causes

Some Cancers• Environmental Causes of Cancer• Evolving Cancer • Key Concepts

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Cancer is Genetic, But Usually Not Inherited

• Whether cancer runs in your family or not, cancer is estimated to affect one out of every three people.

The followingchart is from the 2008 Cancer Registry

Cancer and Genes

• Somatic mutationsAre not passed on to the next generation and it happens in the course of a person’s lifetime usually later on in life. Most cancer mutations occur in this manner (as referenced in the pie chart).

• Germline mutationsAre passed from generation to

generation.There is a 50/50 chance of inheriting cancer if either parent has a genetic change. This type of cancer can develop if a environmental trigger mutates a somatic cell or if somatic mutation mixes with an inherited gene.

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Characteristics of Cancer

• Cell division – Cancer cells no longer respond to stop signals and therefore can divide at a continuously fast rate if the cancer is a cancerous tumor.

• Look of a cancer cell - Cancer cells look different when compared to normal cells. Cancer cells are rounder. This is also known as dedifferentiated.

• Growth of a cancer cell – Cancers can take many years to grow (ei, lung cancer). Angiogenesis can make the cancer spread further by using the capillary extensions.

Origins of Cancer cells2.) Dedifferentiation:• Cells lose their distinguishing

characteristics (their specializations) due to a mutation occuring as the cells divide.

3.) Loss of balance at tissue level:

• Normal cells favor differentiated cells (or daughter cells).

• Tissues with abnormal balance will favor cells that can divide continually

• Eventually that shift in balance will create an excess amount of stem cells and progenitors which causes a tumor.

4.) Faulty Tissue Repair:• If too many cells divide to fill in the

space left by injured tissue, and those cells keep dividing, an abnormal growth may form.

1.) Activation of stem cells:

• A cancer cell may descend from:

– A stem cell that produces differentiated daughter cells (specialized cells) that retains the capacity to self-renew.

– Specialized cells that lose some of their features but can still divide.

• Cancer stem cells produce both cancer cells and abnormal specialized cells

• Cancer stem cells are found in cancers of the brain, blood, and epithelium (lining tissues such in the breast, colon, and prostate).

There are at least 4 situations that can lead to cancer at cellular level:

Cancer Genes

• When mutations activated oncogenes or inactivate tumor suppressor genes, cancer occurs.

• Proto-oncogene: A gene that normally triggers cell division when it is appropriate.

• When proto-oncogenes are turned on at the wrong time or place they function as “oncogenes”. This may be the result of either a mutation or a change in expression of the wild type gene.

• Also, a proto-oncogene that is moved near a gene that is highly expressed then it will also be rapidly transcribed.

• Example: Proto-oncogenes are normally activated at the site of a wound. If it is activated at a site other than the wound (as an oncogene) it still stimulates mitosis and bumps up the growth factor production. These new, un-needed cells become a tumor.

Cancer Genes

Increasing expression in a new location:• Placing proto-oncogene near a gene

that boosts its expression.• Moving proto-oncogene next to a

gene that is normally very active.– This can happen when a chromosome is

inverted or translocated, placing the gene in an new environment.

– When translocation or inversion places a proto-oncogene next to an antibody gene the immune system contributes to cancer.

Fusion Proteins with New Functions:• When a proto-oncogene moves near

another gene and the gene pair is transcribed and translated as if it were one gene.

– The double gene product, called a fusion protein, activates or lifts control of a cell division.

Receiving a Too-Strong Division Signal• When a proto-oncogene recieves

too many signals to divide the gene will replicate until it causes a tumor.

• Some cancer results from loss of a gene that normally suppresses tumor formation by sending growth-inhibiting signals.

• Unlike activating an oncogene (which usually gains a function) a tumor suppressor gene mutation usually removes a function.

• Some of the best studied tumor supressor genes are:

– Retinoblastoma: a rare childhood eye tumor

– P53 gene: a single gene that causes a variety of cancers when mutant

– BRCA1 (Breast cancer predisposition gene 1): Familial breast cancer

• Encodes a large protein that is normally in the nucleus, where it activates transcription of the genes that respond to p53 protein.

• BRCA1: When functioning properly they are necessary for DNA repair

Activating an oncogene: Tumor Suppressors

Stages in the Development of

CancerOne example of such a misfortunate event, is the

rapid development of brain tumors:• A protein called P53, with in the structure of

our chromosomes, seizes to withhold the development of tumors.

• Followed by an interruption on chromosome 9, creating an error in the chromosomes immunity to cancer.

• As the genes cell cycle freezes growth develops on chromosome 7, putting mitosis to a halt.

• At the last stage of the tumors growth , the existence of chromosomes 10 mysteriously vanish.

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Cancer is commonly formed in

the instability of genes• A mutation is found when the

inner chromosomal alignment of a gene becomes imbalanced .

• The whole genome risks instability at the cost of the gene known as the “gatekeeper” (who is in charge of directing the correct balance of somiotic cell division and the balance of natural cell death).

• If the gate keeper does not delegate the motions of the cells properly , a mutation could occur leading to cancer.

• Once a gene has mutated into a cancerous condition. The affect and stages of the mutation begin to unfold, in the depths of our chromosomal structures .

BUB1B (above) is an example of inherited cancerous genes found commonly in young children.

The cause of cancer is greatly impacted by genetics.

Preventing Cancer

• Although preparation or prevention of a brain tumor may be impossible to achieve. Such inheritable cancers like colon cancers can be prevented . Thanks to the research of Doctor Eldon Gardener in 1947, who uncovered the link to the genetic inheritance of colon cancer.

• In a current day action towards the prevention of cancer. Doctors today can check the colon for polyps, a growth in the colon that can lead to cancer.

• The other preventive method is the ability to check stool samples for APC, a protein when found nonexistent in ones gene structure can lead to growth of colon cancer.

• The effect of such an inherited mutation causes the lining of the colon not to die off in its three day existence like it is supposed to.

By knowing your genetics

Preventing Cancer• The website

http://www.therapeasecuisine.com gives information on how to personally prevent cancer. Listing ideas like, “Eat more variety of vegetables and do not use supplements that protect against breast cancer.”

• Even our text book list off suggestions of helpful choices to make in our diet such as, “Vitamins D and E, soy bean compounds, green tea and certain anti- inflammatory drugs.”

• Being aware of occupational hazardous such as fumes, and chemicals, you may breath in at work could potentially bring fourth the effect of cancer.

• Population studies, in which communities bear recessive forms of cancer. Under go group research have found environmental impacts and genetic similarity.

• Case- control studies have also been created to watch over a persons life and the environment of one that eats a diet high in vegetables and exercises regularly and on that does not. Usually the individual with the healthier regimen, out lives of prolongs the occurrence of cancer.

• Though we can not yet fix our DNA or genetic structure, we can make healthy choices in life. The choice to live a life free from smoking, a healthy diet and regular exercise, despite your genetic inheritance could save your life.

By utilizing the environment

Although the fate of cancer can bestow among any one, inheritance of the gene may eliminate the idea of chance replacing it with fate. Yet, regardless of chance or fate, luckily thanks to research and the ability to control some simple environmental factors we may be able to slow down or even delete the existence of cancer amongst our genes.

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Evolving Cancer Diagnosis and Treatment

• It is now possible to predict the likelihood of certain cancers.

• A few cancer treatments include: surgery, radiation, and chemotherapy.

– Surgery: Removes tumors– Radiation and Chemotherapy: non-selectively destroys rapidly dividing

cells• If a patient does radiation and chemotherapy, they will need drugs to

protect them from harmful side effects.

• New drugs have been discovered to fight specific types of cancer.

• Nowadays, we have more than fifty drugs that can stop the blood supply to tumor.

• Using drugs and chemotherapy are useful ways to cure cancer but it means the patient will undergo a longer treatment.

• There are several ways to find cancer but they don’t always pinpoint the cause requiring further examination.

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Key Concepts:• Cancer is genetic, but not necessarily inherited.• Cancer cells have different gene expression profiles

compared to the cells from which they descended.• Cancer is caused by loss of cell division control.• 4 situations at cellular level lead to cancer:

• Activation of stem cells that produce cancer cells, dedifferentiation, loss of balance at tissue level, and faulty tissue repair

• Single genes (oncogenes and tumor suppressor genes, when mutant, can cause cancer.

• Proto-oncogenes normally control cell cycle and become oncogenes when they mutate, moved next to a highly expressed gene, or form a fusion protein.

• Mutations in tumor suppressors removes a function• A single mutant gene can destabilize chromosomes

causing a predecessor of cancer.• Treatments for cancer target the characteristics of

cancer cells.

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ReferencesInternet: Author Unknown 2008, 2008 Cancer Registry Report. Washington Adventist Hospital, http://www.adventisthealthcare.com/WAH

Internet: Author Unknown, Mutation Types in Human Cancer. Nature, http://www.Nature.com

Internet: Author Unknown, BUB1B human: BUB1 budding uninhibited by benzimidazoles.http://www.cellmigration.org/resource/discovery/geiger/geiger_rnai/images2/hr/thumbs/BUB1B_HR.jpg

Internet: CartoonStock.com, “Antioxidants”. http://www.cartoonstock.com/directory/a/antioxidants.asp