question

All forms of cancers can be inherited

answer

False; The predisposition toward cancer or increased risk of cancer can be inherited because of a single mutated gene that is passed down.

question

Complete penetrance

answer

If the inherited mutation is in a critical tumor suppressor gene, the probability of developing cancer can be 100% during the lifetime of an individual.

question

Familial Cancers

answer

Cancers that arise due to inheritance are called familial or hereditary cancers. Due to the fact that mutations can be passed on through generations within a family.

question

Penetrance of the gene:

answer

the % of individuals with the gene mutation that develop cancer.

question

Incomplete penetrance:

answer

even though a mutation in a critical gene is inherited in members of a family and individuals may be homozygous dominant or recessive for the trait, not all will get cancer (only 80-90%). Why?

question

4 reasons behind Incomplete penetrance:

answer

1.)The onset of symptoms is often age related, may have 7% penetrance at 7 yrs, 95% at 60 years of age. Why? 2.)Environmental co-determinants for example nutrition, smoking, other carcinogens affect the % that develop cancer. 3.)Other genes act as genetic cofactors and epigenetic regulation of expression of mutated gene(s) can occur. 4.)Oncogenic viruses, immune response genes may affect penetrance.

question

Example of this?

answer

BRCA1 and BRCA2 mutations usually mean an elevated risk of breast and ovarian cancer, but environmental and behavioral modifiers exist: number of pregnancies, history of breast feeding, smoking, high fat diet, and perhaps HMTV may all affect penetrance.

question

Origins of the Rb gene

answer

A rare childhood cancer of the retina called retinoblastoma.

question

Retinoblastoma

answer

a childhood cancer of the retinal (nerve) cells of the eye, most common eye neoplasm of children. It can move along the optic nerve, migrate to the brain.

question

Opthalamascope:

answer

can detect tumors before they invade-90% cure rate.

question

Two forms of retinoblastoma

answer

Heritable and non heritable.

question

The hereditary (familial) form

answer

both eyes, or bilateral retinoblastoma: 1/3 of the cases. All cells in the body have one inherited mutation, risk of other cancers as well. These children are thus heterozygous for the mutation. Figure 8-2: 50% chance that child will inherit gene and develop family if family member posses rb gene.

question

Sporadic(random) form:

answer

one eye, unilateral : 2/3 cases. Mechanism: The inheritance pattern shows that the Rb-1 gene acts like a Mendelian dominant gene on chromosome 13. It is an anti-oncogene or tumor suppressor gene.

question

Two Hit model:

answer

Fig 8-3 in text. (Left side of diagram)-Children born in families with a hereditary pattern of retinoblastoma have a 50% chance of inheriting a defective RB gene from a parent who is a RB survivor (parent who is heterozygous for RB). A child who inherits the defective RB gene will have the mutation in every body cell. If the good copy of the RB gene then undergoes mutation in the in just a single retinal cell, both RB genes will be defective and cancer will arise. (Right side of diagram)-In families with no histories of retinoblastoma, children are born with 2 good copies of the RB gene. The nonhereditary form of retinoblastoma will then arise only in the unlikely event that both copies of the RB gene undergo mutation in the same cell

question

Older students-

answer

little risk from developing RB, due to the fact that our retinal cells are all terminally differentiated. HOWEVER, light exposure takes its toll on retinal cells, and only macrophages can prevent blindness due to aging. Moral of story: protect your eyes as much as you can.

question

RB gene

answer

a tumor suppressor gene: a gene whose absence leads to cancer.

question

What does the RB gene code for? and what does the product of the gene do?

answer

Rb gene stops the cell cycle. Its protein stops cells at the G1 Restriction Point if DNA mutations need repair. Thus it suppresses the development of cancers.

question

Normal function of RB?

answer

to regulate cell division.

question

RB=?

answer

tumor suppressor gene, its un-phosphorylated protein stops cells at the Restriction Point.

question

Restriction Point:

answer

A point in the cell cycle just before S phase.

question

Rb if not phosphorylated?

answer

stops cell cycle at restriction point before S phase. Repeat that again to yourself.

question

If Rb phosphorylated?

answer

cells can pass restriction into S phase.

question

Growth factors present during retinal cell development...(ages birth to 6 years)

answer

cause formation of active Cdk- cyclins. They add phosphate to Rb and allow cell division. Retina is fully formed (no growth factors, no cell division by age 6).

question

RB gene is recessive because

answer

both genes require the mutation or deletion before cancer can arise. Deletion of a segment of chromosome 13 can be seen on both alleles. However the cancer risk syndrome states that the development of cancer is a dominant trait because only a single Rb mutation needs to be inherited.

question

True or False: One good copy of the RB gene can keep a cell from being cancerous. The Rb protein is made inside the cell from the good copy and the protein can block a cell at the restriction point- even when there is a mutated oncogene around. This certainly makes the RB gene seem dominant in preventing cancer.

answer

True! This is known as "Normal cell phenotype."

question

Inheritance risk for developing cancer:

answer

Since 50% of children are at high risk, it seems as though they have inherited a dominant gene that is "causing" cancer.

question

Transformed phenotype of a cell:

answer

since loss of a single copy is not enough to transform a cell, both copies needed to be mutated it is referred to as a recessive gene. Normally a dominant trait takes over control of a cell when the protein is made. But in retinoblastoma cell it is the absence of the protein that transforms the cell.

question

If Rb gene is involved in restraining cell proliferation, and if it is mutated in every cell of the body in those who inherit it as a recessive- why not other cancers?

answer

They do affect other cancers. Higher incidence of leukemias and other forms of cancers are seen.

question

Are mutations in Rb seen in non-familial cancers?

answer

Yes. Look at mendelian pattern of inheritance.

question

Three types of cancers that cause mutations in RB?

answer

Lung cancers (cigarette smoke), bladder cancers, and breast cancers

question

Familial Adenomatosis Polyposis-

answer

inheritance of mutated APC tumor suppressor gene. 7,500 cases per year of familial colon cancer. Only accounts for 5% of non-familial colon cancer cases

question

APC gene

answer

adenomatosus polyposis coli, aka a tumor suppressor gene. "Two hit" model for this cancer also but we know for a fact that at least four other genes involved..

question

Is the APC gene involved in other cancers?

answer

Yes. bile duct, small intestine, and stomach.

question

Mechanism of Action:

answer

Inhibits the action of the Wnt signaling pathway.

question

Int signaling pathway is important in...

answer

regulating growth of epithelial cells lining the colon, stomach etc.

question

Figure 8-5 in text

answer

Li-Fraumeni Syndrome- In families with this syndrome, roughly half of the offspring develop cancer(red symbols). The cancers are of a wide variety of types, and a single person may develop several different types of cancer in succession. Note here also: Inheritance pattern of cancer developing, gene appears dominant. At cancer cell level it is a recessive gene because both copies must be mutated.

question

Tumor suppressor genes have a...

answer

gate keeper function, which stops cell proliferation.

question

DNA repair enzymes exhibit a...

answer

caretaker function, which repairs mistakes in DNA.

question

DNA repair enzymes (Caretakers): If the caretaker function is lost, then there is....

answer

an accelerated rate of mutation.

question

Xeroderma pigmentosum-

answer

derma(dermis)-for skin cancers caused by Inherited defect in excision repair enzymes.

question

Camp sundown

answer

special after-dark summer camp for children with xeroderma pigmentosum, a rare genetic disorder that results in a sensitivity to ultraviolet light. Those with XP start blistering after just a few minutes in the sun.

question

Excision repair-

answer

seven genes designated XPA through XPG code for required repair enzymes.

question

Pedigree of Xeroderma Pigmentosum:

answer

1. must inherit TWO mutated copies 2. Chances of inheritance if both parents are carriers: 25%, 3. Thus exhibits a recessive pattern of inheritance- neither parent exhibits the cancer. (Not the 50% seen with tumor suppressors wherein the parent often shows with cancer)

question

Figure 8-7

answer

Pedigree of Typical Xeroderma Pigmentosum- Xeroderma pigmentosum requires TWO mutant copies of the same gene to be inherited, one from each parent. If both parents carry such a single mutation, they will show no disease symptoms but will function as "CARRIERS" who can now pass on the gene to their children. Each child will have a 50% chance of inheriting the mutant version from each parent, so the overall probability of inheriting both mutations and developing XP is 25% (50%x50%=25%).

question

Figure 8-8: Dominant inheritance cancer risk syndromes vs. Recessive Cancer Risk Syndromes:

answer

KNOW figure! ** Both copies of tumor suppressor gene must be recessive, and defective, MUST be disrupted before cancer arises.

question

Figure 8-8: Recessive cancer-risk syndrome

answer

In hereditary cancer-risk syndromes exhibiting a recessive pattern of inheritance, ex: xeroderma pigmentosum, 2 defective copies of the a tumor suppressor gene must be inherited to create a high risk of developing cancer.

question

Figure 8-8: Dominant cancer-risk syndrome

answer

In cancer-risk syndromes exhibiting a dominant pattern of inheritance, such as familial retinoblastoma, inheriting a single defective tumor suppressor gene is sufficient to confer a very high risk of developing cancer. Having 1 good copy of the gene allows the formation of cancer to seize, but gives a strong rise to the likelihood that cancer can develop. However, mutation of the second copy of the gene (Normal gene) is required before cancer actually arises.

question

Hereditary non-polyposis colon cancer

answer

Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, and skin.

question

Dominant or Recessive?

answer

Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene in each cell is sufficient to increase cancer risk. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer. **inherit one single mutant copy of a gene coding for mismatch repair enzymes.**

question

Mismatch repair-

answer

a repair that occurs during DNA replication

question

Eight genes involved

answer

True. Any one gene may be involved.

question

Only __% of all breast cancers show this inheritance?

answer

10%

question

What are the two major genes that are known for breast cancer inheritance?

answer

BRCA1 and BRCA 2.

question

Inheritance of mutated genes:

answer

: 40-80% risk of developing breast cancer. 15-65% risk for ovarian.

question

Why not 100%??

answer

Even if inherit the mutated BRCA genes, the risk depends on when you were born! Must be some non-genetic factors! Diet? Smoking? 1940- women enter workforce.

question

Figure 8-9

answer

Effect of Birth Year on Breast Cancer Risk from BRCA: women born after 1940 who carry mutations in the BRCA1 or BRCA2 genes have higher breast cancer rates (at any given age) than women born before 1940, who carry the same mutations. This indicates that non genetic factors influence breast cancer risks.

question

Ataxia telangiectasia-

answer

(ataxia lack of coordination and telangiectasis)= dilation of capillaries. * Inherited DNA repair defect that can cause cancer*

question

Problems with Ataxia telangiectasia?

answer

1- 3 years of age: inability to walk, slurred speech, retarded growth, immune deficiency AND 40% risk of cancer- mostly lymphomas and leukemias but many others as well.

question

Gene and problems with Ataxia Telangiectasia?

answer

most die in teens or 20s Gene: ATM - recessive, two must be inherited. Acute sensitivity to Radiation/oxidative stress-

question

Gene functioning for Ataxia telangiectasia-

answer

detecting DNA damage (By radiation) and sending signal to p-53

question

Bloom's Syndrome:

answer

short stature, immune deficiency, sun sensitive skin, cancer before age 20, lymphoma and leukemia. * Inherited DNA repair defect that can cause cancer*

question

Gene and Gene function of Bloom's syndrome?

answer

Gene:BLM -recessive pattern Gene Function: codes for DNA helicase used to unwind DNA during repair.

question

Inheritance of Mutated Proto-oncogene

answer

Multiple endocrine neoplasia. Gene: RET that codes for a receptor on surface of endocrine cells (pituitary, thyroid, pancreas etc) A gain of function mutation, Mutant gene: An oncogene protein that is always active as a receptor. Receptor on endocrine cells do not need a signal from a growth factor. Cancer is usually a thyroid cancer

question

Inherited Defects in other systems that increase risk for cancer:

answer

Primary immune deficiencies (lack of thymus etc) Induced Immune deficiencies: HIV Immmune deficiency mostly leads to lymphomas and leukemias often by EBV. Inherited defects in liver metabolic enzymes to remove carcinogens.

question

Are there racial differences in risk for cancer?

answer

Melanoma- 15X higher in whites- melanin protection. Colon, lung and prostate higher in blacks- melanin blocks production hormone D. Note: Educated blacks have a lower incidence for Colon, lung and breast cancer than whites. Due to socioeconomic variables? Tobacco? Alcohol? Nutrition? Obesity? Lack of exercise? Protection from cancer by cell phones?

question

Figure 8-11

answer

Racial Differences in Cancer Incidence: (left)- Blacks living in the US have higher cancer rates than whites for most common cancers, including prostate, lung, colon cancers although not breast cancer. (right)- when cancer rates are compared among individuals with comparable levels of education, blacks have similar (or even lower) cancer rates than whites. Thus, many of the disparities in cancer incidences observed among blacks and whites are probably linked to socioeconomic variables rather than to genetic differences.

Bio Cancer Ch.8- Heredity and Cancer – Flashcards

Unlock all answers in this set

Haven't found what you were looking for?

Search for samples, answers to your questions and flashcards