Topic 6 Part 3 Cancer genetics

Question 1

Sporadic cancer

Answer 1

1. Cancer that occurs usually as a result of environmental exposure or unknown factors and does not have any observable pattern of inheritance within a kindred.
2. Usually causes disruption of normal regulation of cell division in somatic tissues.
3. The person cannot pass on a predisposition for the cancer to his or her children because these mutations are acquired only in the tissues that develop the cancer.

Question 2

Familial cancer

Answer 2

1. Cancer that occurs at a higher-than-expected frequency within a kindred but does not demonstrate any observable pattern of inheritance.
2. Usually associated with older ages of onset.
3. Because there is no specific pattern of inheritance, no genetic testing can be recommended. Risk for these cancers may one day be detectable through genome-wide association studies (GWAS).

Question 3

Inherited cancer

Answer 3

1. Cancer that occurs with an observable autosomal dominant pattern of inheritance among much younger-than-expected individuals in a kindred. 5-15% of cancers.
2. Usually associated with younger ages of onset. Predisposition testing is available to the person who has a positive family history for an inherited cancer.
3. Example: BRCA1 suppressor gene mutations can be passed down and significantly increase a person’s risk for breast cancer.

Question 4

All cancers are caused by _

Answer 4

Genetic mutations.

Question 5

Germline mutation

Answer 5

1. A mutation that is present in the egg or sperm of a parent that is present in all cells of an offspring.
2. Heritable mutation that results in family cancer syndromes.

Question 6

Somatic mutation

Answer 6

1. A mutation that occurs in non-germline tissues (e.g., the breast) that affects only that tissue. Most common (85-90%) cause of cancer.
2. Non-heritable mutation. Example: Lung cancer is caused by environmental exposure to carcinogens, not due to hereditary factors.

Question 7

Mutations in _ are the most common mutations that lead to the development of cancer.

Answer 7

DNA repair proteins. (BRCA1 and BRCA2 are examples of this.)

Question 8

Tumor suppressor genes (“defective brake”)

Answer 8

1. Genes which generally inhibit cell cycle progression.
2. Mutations in these genes lead to a lack of control of cellular processes such as proliferation and DNA damage checkpoints - uncontrolled cell division occurs.

Question 9

Oncogenes (“jammed gas pedal”)

Answer 9

1. Genes which, when mutated, lead to increased proliferation and/or survival of cells, leading to malignant transformation.
2. Mutation of proto-oncogenes (normally functioning genes that become overactive when mutated) leads to activation/over-activation - the speed of cell division is increased.

Question 10

Characteristics of hereditary cancers

Answer 10

1. Young age of onset.
2. Multiple family members with the same type of cancer - familial aggregation.
3. Multiple primary tumors in the same individual.
4. Bilateral tumors in same organ.
5. Tumors occurring in abnormal sex (breast cancer in males).

Question 11

In families with hereditary cancer, the children have a _ chance of inheriting that cancer risk from a mutation-positive parent.

Answer 11

50%.

Question 12

For women with a BRCA mutation, mastectomy/ovarectomy decreases the risk of cancer in those organs by _

Answer 12

90%.

Question 13

A woman at average risk for breast cancer should have a mammography every _ years beginning at age _

Answer 13

1-2 years; age 40.

Question 14

A woman at high risk for breast cancer (BRCA mutation positive) should have a mammography every _ years beginning at age _

Answer 14

1 year; age 25-35.

Question 15

Lynch syndrome/HNPCC (hereditary nonpolyposis colorectal cancer)

Answer 15

1. Caused by a series of mutations in mismatch repair genes. A mutation in the APC gene is present at birth in 80-90% of affected individuals.
2. Early-onset cancer in one of several organs: Right-sided colorectal cancer, endometrium, renal pelvis, stomach, ovaries, brain, skin.

Question 16

Individuals in Lynch syndrome families should have an annual colonoscopy beginning at age _

Answer 16

Age 25 (or earlier if the age of onset within the family is earlier).

Question 17

Tumor heterogeneity

Answer 17

1. When one tumor cell mutation causes multiple effects that promote cancer, such as proliferation, decreased apoptosis, chemotherapy resistance, etc.
2. Makes tumors harder to treat - may kill cells of one type, but other types persist.

Question 18

The Cancer Genome Atlas (TCGA)

Answer 18

Massive, multi-site sequencing and annotating effort to characterize a set of mutations found in common cancers to allow for better targeted treatments.

Question 19

By which process does “initiation” assist in cancer development?

Answer 19

Inflicting mutations at specific sites on the exposed cell’s DNA.

Question 20

Which statement best describes the role of tumor suppressor genes in cancer development?

Answer 20

Tumor suppressor genes control or modify the activity of oncogenes, reducing the risk for cancer development.

Question 21

What is the result of a mutation occurring in a suppressor gene?

Answer 21

Loss of an existing function. [When a suppressor gene is damaged, it loses some or all of its function and can no longer express its products in the proper amounts to control oncogene expression.]

Question 22

Why are people who have poor DNA repair mechanisms at greater risk for cancer development?

Answer 22

Their somatic mutations are more likely to be permanent. [DNA damage occurs on a daily basis for any person. Most of this damage is repaired by DNA repair mechanisms before cancer can develop. For those people who have poor DNA repair mechanisms, these constant and random DNA mutations do not get repaired and are permanent, often constituting initiation.]

Question 23

Which feature is associated exclusively with sporadic cancers?

Answer 23

It occurs at the same frequency within a kindred as in the general population. [Sporadic cancers occur usually as a result of environmental exposure or unknown factors and do not have any observable pattern of inheritance within a kindred nor do they have an increased frequency within a kindred.]