Animal models of cancer
Definitions SNPs
Single nucleotide polymorphisms (SNPs) –
variations in the DNA sequence between
individuals occurring in otherwise identical regions
May be:
o In the protein coding sequence and change the
protein code (when does a SNP become a
mutation?)
o In the protein coding sequence but silent
o In non-coding regions and functional – affecting
gene expression or regulation (e.g. splicing)
o In non-coding regions and non-functional (but
potentially linked to unknown functional
variations)
o Can cause gene to be expressed at higher or lower
levels, if for example a tumour suppressor gene,
could cause increased susceptibility to cancer
Haplotype – a set of DNA variations (sets of SNPs)
that tend to be inherited together
o Refers to a set of single nucleotide polymorphisms
(SNPs) found on the same chromosome that are in
linkage disequilibrium – rarely separated by
chiasmata events at meiosis
Odds / odds ratio / relative risk / hazard ratios –The
relative difference in risk that an individual has
when they have a particular risk allele compared to
those that do not e.g. increase/decrease by 1.15 or
0.8
Absolute risk (could be lifetime or within a time
period)– Absolute numbers at risk e.g. an absolute
lifetime risk of 0.5 (%) of getting a disease means
out of every 1000 people, 5 will get the disease in
the course of their lives
Consider the two together Risk factors for cancer
– In a reference population without the risk Aging – most cancers req(uire 4 to 6
allele, absolute risk is 0.5 x 1(baseline) = mutations minimum to progress from normal
0.5 = 5 in 1000 cell to malignant invasive cell – takes time
– In individuals with the risk allele, and there are surveillance mechanisms to stop
absolute risk is 0.5 x 1.15 = 0.575 =approx. it
6 in 1000 Genetics – SNPs and cancer genes (e.g.
– (500 in 100,000 vs 575 in 100,000) BRCA1, BRCA2) typically identified through
studies of cancer families or whole
But risks are combinatorial populations
Infections
Immune surveillance failure
Lifestyle- alcohol, smoking
Environmental exposure- carcinogens
Hormonal exposure- oestrogen in breast C
and androgen in Prostrate C
Tissue microenvironment
Definitions SNPs
Single nucleotide polymorphisms (SNPs) –
variations in the DNA sequence between
individuals occurring in otherwise identical regions
May be:
o In the protein coding sequence and change the
protein code (when does a SNP become a
mutation?)
o In the protein coding sequence but silent
o In non-coding regions and functional – affecting
gene expression or regulation (e.g. splicing)
o In non-coding regions and non-functional (but
potentially linked to unknown functional
variations)
o Can cause gene to be expressed at higher or lower
levels, if for example a tumour suppressor gene,
could cause increased susceptibility to cancer
Haplotype – a set of DNA variations (sets of SNPs)
that tend to be inherited together
o Refers to a set of single nucleotide polymorphisms
(SNPs) found on the same chromosome that are in
linkage disequilibrium – rarely separated by
chiasmata events at meiosis
Odds / odds ratio / relative risk / hazard ratios –The
relative difference in risk that an individual has
when they have a particular risk allele compared to
those that do not e.g. increase/decrease by 1.15 or
0.8
Absolute risk (could be lifetime or within a time
period)– Absolute numbers at risk e.g. an absolute
lifetime risk of 0.5 (%) of getting a disease means
out of every 1000 people, 5 will get the disease in
the course of their lives
Consider the two together Risk factors for cancer
– In a reference population without the risk Aging – most cancers req(uire 4 to 6
allele, absolute risk is 0.5 x 1(baseline) = mutations minimum to progress from normal
0.5 = 5 in 1000 cell to malignant invasive cell – takes time
– In individuals with the risk allele, and there are surveillance mechanisms to stop
absolute risk is 0.5 x 1.15 = 0.575 =approx. it
6 in 1000 Genetics – SNPs and cancer genes (e.g.
– (500 in 100,000 vs 575 in 100,000) BRCA1, BRCA2) typically identified through
studies of cancer families or whole
But risks are combinatorial populations
Infections
Immune surveillance failure
Lifestyle- alcohol, smoking
Environmental exposure- carcinogens
Hormonal exposure- oestrogen in breast C
and androgen in Prostrate C
Tissue microenvironment
