Cancer as a preventable disease Flashcards
Tobacco
Smoking largest preventable cause of cancer (22% of all cancer deaths)
73 carcinogenic chemicals in smoke
Nicotine not a carcinogen but is addictive
Mutations in KRAS and TP53
Obesity
Adipocytes release adipokines (signal molecules) which drive proliferation
Oestrogen release (drives growth of hormone responsive cells)
Recruitment of macrophages leading to chronic inflammation
Disruption of insulin signalling
Infections and cancer
Chronic infections cause 20% of all cancers
Primarily caused by H. pylori and HPV
Gardasil9 vaccine against HPV. Engerix-B against HBV
Hepatocellular carcinoma
Liver cancer
HBV causes 50% of cases
HCV causes 15% of cases
Aflatoxin contamination of food (28%)
Alcohol abuse (alcoholic fatty liver disease)
Obesity (non-alcoholic fatty liver disease)
HBV/HCV and liver cancer
Chronic inflammation causing an increase in ROS. Results in cell damage
Immune cell infiltration of liver
Aflatoxin B1
Mycotoxin produced by Aspergillus spp.
Activated in the liver by cytochrome p450 enzymes
Reacts with DNA to form an adduct
Oestrogen and breast cancer
75% of breast cancers are positive for the oestrogen receptor
Oestrogen receptor (TF) binds oestradiol and activates
Binds ERE (oestrogen response element) in complex with a co-activator.
Activates ER target genes leading to proliferation
Aromatase inhibitors
Prevents oestrogen synthesis in peripheral fat (main source post-menopause) so stops ER gene transcription
Aromatase synthesises oestrone/oestradiol
Doesn’t work in the ovaries
Side effects are menopausal symptoms, joint pain and osteoporosis
SERMs
ER antagonist in breast tissue
Prevents binding of oestrogen to co-activator
Can act as an ER agonist in other tissue (bone/endometrium)
Increased risk of stroke/endometrial cancer
Breast feeding and cancer
Reduces oestrogen levels and fully differentiates tissue
Massive epithelial apoptosis may remove cells with initial DNA damage
