The Molecular basis of cancer 1 Flashcards
what DNA damage is inherited?
germ line errors (from parents)
what DNA damage is acquired?
somatic errors (from every other cell in the body)
Which cells have the defected DNA in inherited cases?
every cell in the body. hence every cell in the body is at a predisposed risk.
Which cells carry the mutation in acquired cases?
only the cancer cells.
How many cancer cases can be attributed to genetic factors?
10%
What are some things that can cause dna damage?
radiation. viruses. bacteria, chemical carcinogens. age. diet. uv light.
why does the incidence of cancer increase with age?
- cancer takes decades to go form single cell to tumour.
- lifetime exposure to carcinogens and environment exposure.
- as you age, dna repair mechanisms don’t work as well.
what can radiation do?
cause double stranded DNA breaks.
what do cancer cells do in terms of p53?
they inactivate p53 early in development. hence, the cell does not arrest when the DNA is damaged and continue to go on and divide.
what percentage of carcinogens that we are exposed to in our diet are made up of “natural” carcinogens?
80%.
What type of diet predisposes to cancer?
high fat and low fibre diet.
Why does that diet predispose to cancer?
when fat is released, a lot of chemicals are released. fibres allow the food to stay in the gut for longer. the chemicals are thus there for longer.
what types of cancer does obesity predispose to?
breast, prostate, stomach.
how does obesity link to cancer?
people who are obese have an imbalance of sex hormones. thus they produce more oestrogen in their fat. this drives cells to grow (especially in breasts), predisposing to different types of cancers.
what does chronic inflammation do to cancer?
it predisposes to cancer. hepatitis of the liver can predispose to liver cancer. inflammatory bowel disease can predispose to bowel cancer.
What cells are susceptible to DNA damage?
- rapidly dividing cells are particularly susceptible to genetic damage and caner - they cycle faster through cell cycle, less time for DNA repair mechanisms.
- in somatic cells that divide frequently (bone marrow, gut cells, skin cells), carcinogens cause DNA damage, causing mutations of one base to another.
when does the accumulation of DNA mutations occur?
- substantial mutations.
- loss of DNA repair enzymes.
- less time for the DNA repair mechanisms.
how many cases of cancer can be accounted by viruses?
15%.
name some viruses and their cancer?
- nasopharynx/lymphomas = epstein-barr virus.
- liver cancer = hep b
- kaposi sarcoma = kaposi sarcoma virus.
- anogenital cancer = papillomavirus
- t cell leukemia = human t cell leukemia (HTLV-1)
how do viruses cause cancer?
they affect cell’s DNA leading to over expression of a protein or more active protein.
how many cancers result from inheritance of a mutated gene?
10%.
reason for some familial aggregation?
- shared exposure to carcinogens.
- genetic predisposition.
- mix of both.
what is the risk of a person developing cancer if their parent or sibling develops the cancer at a young age?
2 times.
is penetrance constant or variable?
variable.
what is non-penetrance?
an individual who inherits the mutation, but does not develop the disease.
what is anticipation?
when an offspring develops the cancer at a younger age in succeeding generations.
what is photocopy?
individuals who develop the disease due to environmental factors, but did not inherit the mutation.
what is penetrance?
the percentage of individuals with a specific gene defect who will get the disease.
What is the penetrance of colon cancer?
100%.
penetrance of breast cancer?
40-70%.
what percentage of breast cancers are due to a genetic predisposition?
10%.
what are hereditary breast cancer genes?
BRCA1 17q
BRCA2 13q
what is the life time risk for sporadic breast cancer in the community?
11%.
compared to the rest of the population, what % of BRCA1 will have breast cancer by 50?
51%
compared to the rest of the population, what % of BRCA2 will have breast cancer by 50
28%
What is the lifetime risk of breast cancer by the age of 70?
83-88%
Life time risk of ovarian cancer in this group of patients with hereditary breast and ovarian cancer syndromes.
16-60%.
what heritage is at an increased risk of an individual having BRCA mutations?
Ashkenazi Jewish heritage.
