Breadt Cancer Genetics Flashcards
Why is angiogenesis a requirement for tumorigenesis (1/6 requirements)
Tumour needs oxygen aupply
What epigentic fsctor causes metastatic breast cancers
HDAC increased reduces exp of ecadherins
Explain what makes up the breast
Lobular units where milk is made then ducts take it down
Epithelial cells make the milk
Myoepithelium surround them as a barrier
Stromal cells also present
In situ malignancy is what
Where cells are malignant but stay surrounded by myopeithelial cells
What is the difference between invasive malignancies and metastatic breast cancer
Invasive means they peoentraye the Myoepithelium barrier and spread to breast connective tissues
Metastatic is where they invade other tissues via lymphatic drainage,neural network or vasculature
What 3 breast event changes occur eg during mestrual cycle, pregnancy, puberty and lactation
Cells will expand, differentiate and then involution occurs to counteract changes
What is this controlled by
Hormones
When is breast cancer risk increased
During early and late menopause
Contraceptive pill
Hormone rt for menopause
Phytoestrogens
Zenoestrogens (mimic hormones)
Why does oestrogen and progesterone promote mutagenesis
Increased cell proliferation
Why is pregnancy seen as protective
Allows differentiation in mammary gland which is protective
What else helps reduce risk
Lactation/breastfeeding
How can this explain demographic incidence
Reduced risk in areas like africa with more pregnancy and breastfeeding
What are the sources of oestrogen for pre, post menopausal women and men
Pre- ovarian androgens converted
Post- adrenal androgens converted
Men- testicular androgens converted
Converted to estrogens by aromataae
Why may obese people have more aromatise and so bigger risk
Present in adipose tissue
Give examples of anti-oestrogen treatment which could reduce risk
Aromatase inhibitors
Serms- antagonist of er binding
What do serms like tamoxifen stop
Cell proliferation / block cell cycle
Explain how the er can affect genes for cell proliferation,apoptosis and differentiation
It has tf activity and can interact with other tf in nucleus like ap-1
Which genes are usually gained or lost in breast cancers via mutations or epi genetics
Loss of tumour suppressors via gene exp or mutation
Gain of oncogenes via mutation in Proto-oncogenes
What are proto-oncogenes
Genes which when mutated can cause cancer
They usually regulate cell growth
What % of breast cancer is hereditary (I.e dominant pattern of inheritance and high penentrance)
5%
What % does sporadic bc make (ie de novo variants/ mutations)
80%
What does familial breast cancer mean
Runs in family but not Mendelian inheritance- either shared environment, by chance or low risk alleles
What are the major hereditary cancer genes (autosomal dominant)
Brca 1/2 and they are tumour suppressirs
Which brca gets commonly methylated
Brca1
