20 - Cancer Genetics Flashcards
Cancer is a genetic process, what does this mean?
Changes/mutations occur over time and can lead to cancer.
Other factors can also play a role such as lifestyle (smoking), exposures (environmental/occupational), and internal factors (viruses, hormones).
What are the causes of cancer? What are the majority of cancers?
Majority are sporadic - 60%, with onset after 50 years, and with that person being the only person in the family to have that cancer.
Only 10% is hereditary and attributed to the inheritance of a single gene.
30% is considered familial due to multiple genes and environmental factors.
What is the difference between hereditary and non-hereditary retinoblastoma?
In hereditary, a mutation in one copy of the RB gene is inherited in all body cells and a mutation in the second copy occurs in one or mor eretina cells.
In non-hereditary, a mutation in one copy of RB gene occasionally occurs as cells divide and a mutation in the second copy of the RB gene occurs in one or more cells.
Describe the difference between hereditary predisposition and acquired cancers?
This predisposition is inherited in a dominant manner. Most display aut dominant inheritance (of the predisposition of cancer).
Somatic mutations follow the two hit hypothesis in which both alleles of particular gene are altered. This is just speaking to the genomic alterations within that tumor cell. These are NOT within the gonads of the parent. (NOT A RECESSIVE HYPOTHESIS, nothing to do with inheritance)
Describe how mutations can cause acquired cancers?
- Normal genes regulate cell growth (tumor suppressor genes are the brakes to the car)
- 1st mutation in a susceptible carrier ( you nay have a stuck gas pedal but you can still pump your breaks)
- 2nd mutation or loss (breaks are out and gas is stuck down - car crashes into cancer wall).
What are some clues that a cancer is hereditary?
- Younger than expected age of dx
- Many affected family members
- More than one generation affected
- Pairing of cancers (breast & ovarian, colon & endo)
- More than one cancer in the same person
- Ashkenazi Jewish heritage
What are different testing methods for genetic testing?
- Single site analysis - looks at certain spot in gene
- Multisite analysis (Ashkenazi Jewish)
- Sequencing
- Deletion/duplication testing
- Next Gen sequencing
- gene panels
- whole exome sequencing
- whole genome sequencing
What is the benefit of next gen sequencing? What are benefits of genetic testing in general?
Many genes are implicated in cancer, so testing multiple genes simultaneously can be more time and cost effective.
Genetic testing in general may:
- provides risk info
- info useful for medical management
- Leads to cancer PREVENTION and EARLY detection
- may releieve anxiety
What are risks and limitations of genetic testing?
Risks: emotional proces and insurance discrimination
Limitations: not available to detect all causes of hereditary cancer, continued risk for sporadic cancers, some management strategies not proven effective.
What are the three classifications of a variant?
Positive: deleterious mutation means variant is likely pathogenic (95-98% chance) interpret with caution
Inconclusive: variant of uncertain significance (anything less than 95% significance)
Negative: variant likely benign (interpret with caution),
What is the genetic information nondiscrimination act (GINA)?
GINA is a federal law passed in 2008 that protects individuals from genetic discrimination in health insurance and employment.
- prohibits employers from discriminating based on genetic tests
Does NOT apply to life insurance, long-term care insurance, or disability insurance.
Should a 42 year old women (arrow) be sequenced for BRCA1 and 2? Her family history is displayed here.
Nope, she doesn’t have a strong family history of breast cancer.
In what cases should a woman get genetic testing done to look for predisposition to breast cancer?
- If they have a known BRCA1 or BCRA2 gene mutation
- Have a first degree relative with a BRCA1 or 2 mutation but haven’t had testing done themselves
- Have a lifetime risk of breast cancer >20-25% based on assessment tools
- Had radiation to the chest between 10 and 30 years old
Based on the family history, should this person (arrow) be tested for the BRCA1 and 2 gene mutations? What family member should be tested?
Yes! All of these cancers are rapidly progressing and they are members of a high risk population (Ashkenazi jewish)
Always test the family member who is most severely affected.
Sara comes to you with concerns about her family history of endometrial cancer. She would like to be tested for the lunch genes. What is a significant limitation of tested her, given that she is unaffected? What should be done instead?
A negative result in her would not be reassuring because there are other genes that may be mutated and cause the endometrial cancer in her family.
Her sister (who has endometrial cancer) should be tested to see what is causing her cancer. We know to test her sister becasue she’s the one who got it the youngest.
