Selenium And Cancer Flashcards
In genetics lecture. What defined tumorigenesis
Mutations and damage leading to proliferation signalling, angiogenesis, resisting cell death, metastasis
What is selenium
A micronutrient needed for selenoprotein synthesis
Name some anti carcinogenic properties of seleniproteuns
Antioxidants (ox stress causes cancer)
Immune surveillance
Er stress response
Tumour suppressive/anti proliferation and survival
What are the major antioxidant proteins
Gpx
Where is deficiencies seen due to poor soil content
Europe , China and nz
Explain the small benefit risk window
Deficiency causes diseases like keshans
Suboptimal- increased cancer, cvd and t2d risk
Diabetes seen in supra optimal SELECT study
And selenosis/toxicity in high levels
What do all selenoproteins need to share forking the hierarchy
The selenium is contained in form of selenocysteine (sec amino acid) incorporated during translation
Which stop codon in selenoproteins read to incorporate sec instead
Uga
What does selenoproteins mrna have in 3’ utr
Secis
Explain briefly the steps of translation
Ribosome reads uga and recruits trna sec
It binds to secis
Sec is then incorporated into selenoproteins
Secis needs bound factors like sbp2 and ef which then allows the sec incorporation as it allows recoding uga into a non Stop codon
What happens to proteins low in hierarchy
If not enough sec, uga is a stop codon and truncated protein is degraded
What are some proteins high in hierarchy
Sep15 - er stress
Gpx4 - antiox
What are some low
Gpx1
SelS (er)
Why might selenoproteins be linked to cvd
Oxidative stress causes damage to vascular endothelial cells exacerbating issues like atherosclerosis
What does selS knockout do when er stress builds
Activation of inflammatory pathways like nfkb and apoptosis dysregulation
What did the npc us study find
In those with baseline low se levels, pca and crc risk reduced when given supplements
Why did the select study counteract this
Found no effect on pca risk but increased t2d risk instead
Why did this study differ
Ppts we’re already high in selenium baseline
What did these studies spark
Interest in genetic factors affecting requirements for se
Need to test previous se levels because of the small window
What study type was used to study sep15 snps in prostate cancer
Candidate
What is sep15 relevance in prostate cancer
Helps protein folding and involved in er response
Highly expressed in prostate
Which 2 variants found
Intron variant (gene exp affected in selenium presence)
3’ utr affecting sec incorporation
What did this study conclude from selenium intake
The supplement only improved for those with the ga/gg genotype
As increased survival rates
No effect for A/A
Hence need genotyping before supplementation
Which plasma selenoprotein is responsible for delivering se for other protein Stnrhesis
Sepp/ selenoprotein P
