Hereditary cancer Flashcards
What is the definition of hereditary cancer?
A clustering of cancer in one family due to an inheritable mutation which can be passed from parent to child.
Rank hereditary cancer, familial cancer and sporadic cancer from least to most common.
Sporadic cancer is the most common, thereafter familial cancer and the least common is hereditary cancer.
What is the difference between hereditary cancer and familial cancer?
Hereditary cancer is caused by inheritable mutations, whereas familial cancer is caused by genes and/or other shared factors such as environment and life style.
Hereditary cancer is caused by germline mutations in tumor suppressor genes (TSGs) and proto-oncogenes. Which is the more commonly affected genes?
The tumor suppressor genes (TSGs) are more commonly affected.
What are differences in cancer causing mutations in tumor suppressor genes (TSGs) and proto-oncogenes?
TSGs negatively regulate the cell cycle. Cancer causing mutations in these genes are inactivating, resulting in loss of function. Two hits are needed.
Proto-oncogenes positively regulate the cell cycle. Cancer causing mutations in these genes are activating, resulting in gain of function. One hit is needed.
What is the difference between sporadic and hereditary cancer causing mutations in term of first and second hit?
In hereditary cancer the first hit occur in the germ line cells and the second hit occur in somatic cells. (This means every somatic cell in the individual carries the mutation in one allele.) As for sporadic cancer both the first and second hit occur in somatic cells.
What are the differences between sporadic and hereditary cancer in terms of bilateral/unilateral presentation, onset of disease, and number of tumors?
Hereditary cancer is more likely than sporadic cancer to present bilaterally.
Onset of disease is usually early in hereditary cancer, whereas sporadic cancer usually has it’s onset later.
In sporadic cancer there is usually only one tumor, whereas hereditary cancer often has multiple tumors.
Why is it important to discover families with hereditary cancer?
Early detection of mutation carriers/healthy family member allows better prognosis (and increased survival).
Risk reducing option (such as surgery) may be offered.
Implications for cancer treatment.
What is meant by genetic overlap in relation to genes in hereditary cancer?
Several genes can increase the risk of a single cancer. Several cancers can be associated with a single gene.
Mutations in hereditary cancer genes increase the risk of cancer. The risk is usually divided into high risk mutations, moderate risk mutations and low risk mutations. What is meant by high, moderate and low risk?
In high risk mutation the relative risk (RR) is higher than 5.
In moderate risk mutations the relative risk (RR) is higher than 2, but lower than 5.
In low risk mutations the relative risk (RR) is lower than 2.
True or false: The most common mutations in hereditary cancer are also the ones with the highest penetrance.
False. The most common mutations have the lowest penetrance, whereas rare mutations have moderate to high penetrance.
Which genes are the most commonly associated with hereditary breast and ovarian cancer?
BRCA 1 and BRCA 2.
How are mutations in the BRCA1 or BRCA2 monitored related to hereditary cancers?
Annual mammography from 25 years of age.
Risk reducing surgery (salpigno-oophectory at 35-40 years, risk reducing mastectomy).
Annual PSA from 40 years of age in males - prostate cancer.
What are the criteria for testing for hereditary breast and ovarian cancer genes in patients with cancer?
Breast cancer under the age of 60 years in females.
Breast cancer in males at any age.
Ovarian cancer at any age.
What are the criteria for testing for hereditary breast and ovarian cancer genes in healthy patients?
first degree relative (or second degree with a male between) with one of the following:
Breast cancer under the age of 50 in females.
Breast cancer at any age in males.
Triple negative breast cancer under the age of 60 in females.
Bilateral breast cancer under the age of 60 in females.
Ovarian cancer.
2 relatives with breast or prostate cancer mean age 55.
3 relatives with breast cancer at any age.
