Summary Nutrition and Cancer (HNH-37806)
Prerequisite knowledge
Epidemiology:
Descriptive epidemiology: Frequency/amount of disease or other characteristics in a
population
Analytical epidemiology: study of the cause of disease, exposure-disease association
o Observational study
Cross-sectional study: same moment in time
Cohort study: following in time
Case control study: track back in time
o Experimental study
Randomised controlled trial: random allocation, following in time
Cohort study: following exposed and non-exposed over time and see
what happens to them
Cohort: a group of people who share a common
characteristic
Purpose:
o Study etiological factors: cause of the disease
o Study prognostic factors: predictors of the disease
Case-control study: trace back in time to see if people with a certain
disease had a specific exposure
Suitable for:
o Rare conditions
o When disease slowly develops/have a long latency
period
Advantages:
o Less burden to participants
o Fast and cheap
Case groups
o Incident cases: newly diagnosed
o Prevalent cases: old and new occurrences
Reverse causation
Survivor effect
o Control group: representative to total population
o Hospital controls: patients admitted to same hospital as the cases, but for other
reasons
Randomized control trial (RCT):
Prospective design
To assess the efficacy of an intervention or treatment
Comparison with a control group/treatment
More proof of ‘causality’ than observational study
Outcome:
o Continuous
o Dichotomous (0/1 or yes/no)
Control treatment:
o Regular treatment
o No intervention
1
, o Placebo
Randomization of who gets intervention
Trial designs:
Parallel: people get one treatment and not the other
Cross-over: people receive both treatments by switching halfway
o Randomize treatment order to get rid of time effects
o Can only be used if the exposure has no long lasting effect
o Can only be used for outcomes that are reversible and that can change a short time
period
o Treatments may be separated by a ‘wash-out’ period
Community trial: trial in the population often focussed on primary disease prevention
o Unit of randomization are communities
o Intervention is provided by e.g. GPs, community health centres, local outpatient
facilities
o Suitable design for testing lifestyle interventions that cannot be allocated to
individuals
Quasi-experimental trial: trial without random assignment to the treatment, i.e. without
control group or control treatment
o Investigator assigns exposure
o Pretest/posttest comparison
o Often used in a hospital or public health setting
o Used when:
You are interested in studying cause and effect
You can manipulate the independent variable
You are not able to use a stronger experimental design because it is
unfeasible or unethical
Genetics: heritability of the DNA sequence
Epigenetics: the study of how your behaviour and environment can cause changes that affect the
way your genes work, involving DNA methylation and histone modifications
Seasonal polyphenism: two or more phenotypes are produced from a single genotype in different
seasons
DNA methylation: an epigenetic mechanism used by cells to control gene expression, to turn genes
‘off’ by adding a methyl group to a cytosine
Stable and long-term
Histone modification: epigenetic mechanism to control gene expression by tightening and loosening
the DNA
More dynamic
DNA (-) and histones (+) are attracted to each other
Euchromatin: open chromatin
Heterochromatin: closed chromatin
o Constitutive chromatin: when all cell types have the same closed histone state
o Facultative chromatin: histone state differs by cell type or by time
Histone acetylation: neutralizing histone charge to open chromatin
o Histone acetyltransferase (HAT): enzyme to uncoil DNA and open chromatin
structure
o Histone deacetylase (HDAC): enzyme to coil DNA and close chromatin structure
2
, Histone methylation: process by which methyl groups are transferred to amino acids of
histone proteins to alter gene expression, without altering the positive charge of the histones
Non-coding RNAs: inhibits the transcription of mRNA and has regulatory and epigenetic functions
Small ncRNAs (siRNAs, miRNAs and piRNAs)
o Highly conserved
o Involved in transcriptional and post-transcriptional gene silencing through sequence-
specific base pairing with their targets
Long ncRNAs
o Poorly conserved
o Transcribed RNA molecules greater than 200 nucleotides
o Regulate gene expression by diverse mechanisms
Signal: indicates gene regulation in space and time
Decoy: titrate away transcription factors and other proteins from chromatin
Guide: recruitment of chromatin modifying enzymes to target genes
Scaffold: brings together multiple proteins to form ribonucleoprotein
complexes and affects histone modifications
DNA methylation:
Methyl groups (CH3) are needed and can be derived from dietary methyl donors
S-adenosylmethionine (SAM): major methyl donor in the cell
o methyl group is transferred from SAM to cytosine by
the DNA methyltransferases (DNMTs)
o When SAM donates its methyl group it converts into
S-Adenosyl homocysteine (SAH)
o SAH is consequently converted to homocysteine
(HCY), which can be converted to methionine with the
help of vitamin B12
o Methionine, together with an adenosyl molecule, will
be converted to SAM again
The addition of methyl groups to DNA is
carried out by a family of enzymes called
DNA methyltransferases (DNMTs)
o DNMT1, DNMT3a and DNMT3b
are required for establishment and
maintenance of DNA methylation
patterns
DNMT1 is responsible for
the maintenance of established patterns of DNA methylation
DNMT3a and 3b mediate establishment of new, or de novo, DNA
methylation patterns
o DNMT2 and DNMT3L also have more specialized but related functions
DNMT2 displays weak DNA methyltransferase activity but actually functions
as an RNA methyltransferase
DNMT3L has no catalytic activity but recruits DNMT3a and DNMT3b to their
targets and increases the ability of both DNMT3s to bind to methyl groups,
thus facilitating methylation
3
Prerequisite knowledge
Epidemiology:
Descriptive epidemiology: Frequency/amount of disease or other characteristics in a
population
Analytical epidemiology: study of the cause of disease, exposure-disease association
o Observational study
Cross-sectional study: same moment in time
Cohort study: following in time
Case control study: track back in time
o Experimental study
Randomised controlled trial: random allocation, following in time
Cohort study: following exposed and non-exposed over time and see
what happens to them
Cohort: a group of people who share a common
characteristic
Purpose:
o Study etiological factors: cause of the disease
o Study prognostic factors: predictors of the disease
Case-control study: trace back in time to see if people with a certain
disease had a specific exposure
Suitable for:
o Rare conditions
o When disease slowly develops/have a long latency
period
Advantages:
o Less burden to participants
o Fast and cheap
Case groups
o Incident cases: newly diagnosed
o Prevalent cases: old and new occurrences
Reverse causation
Survivor effect
o Control group: representative to total population
o Hospital controls: patients admitted to same hospital as the cases, but for other
reasons
Randomized control trial (RCT):
Prospective design
To assess the efficacy of an intervention or treatment
Comparison with a control group/treatment
More proof of ‘causality’ than observational study
Outcome:
o Continuous
o Dichotomous (0/1 or yes/no)
Control treatment:
o Regular treatment
o No intervention
1
, o Placebo
Randomization of who gets intervention
Trial designs:
Parallel: people get one treatment and not the other
Cross-over: people receive both treatments by switching halfway
o Randomize treatment order to get rid of time effects
o Can only be used if the exposure has no long lasting effect
o Can only be used for outcomes that are reversible and that can change a short time
period
o Treatments may be separated by a ‘wash-out’ period
Community trial: trial in the population often focussed on primary disease prevention
o Unit of randomization are communities
o Intervention is provided by e.g. GPs, community health centres, local outpatient
facilities
o Suitable design for testing lifestyle interventions that cannot be allocated to
individuals
Quasi-experimental trial: trial without random assignment to the treatment, i.e. without
control group or control treatment
o Investigator assigns exposure
o Pretest/posttest comparison
o Often used in a hospital or public health setting
o Used when:
You are interested in studying cause and effect
You can manipulate the independent variable
You are not able to use a stronger experimental design because it is
unfeasible or unethical
Genetics: heritability of the DNA sequence
Epigenetics: the study of how your behaviour and environment can cause changes that affect the
way your genes work, involving DNA methylation and histone modifications
Seasonal polyphenism: two or more phenotypes are produced from a single genotype in different
seasons
DNA methylation: an epigenetic mechanism used by cells to control gene expression, to turn genes
‘off’ by adding a methyl group to a cytosine
Stable and long-term
Histone modification: epigenetic mechanism to control gene expression by tightening and loosening
the DNA
More dynamic
DNA (-) and histones (+) are attracted to each other
Euchromatin: open chromatin
Heterochromatin: closed chromatin
o Constitutive chromatin: when all cell types have the same closed histone state
o Facultative chromatin: histone state differs by cell type or by time
Histone acetylation: neutralizing histone charge to open chromatin
o Histone acetyltransferase (HAT): enzyme to uncoil DNA and open chromatin
structure
o Histone deacetylase (HDAC): enzyme to coil DNA and close chromatin structure
2
, Histone methylation: process by which methyl groups are transferred to amino acids of
histone proteins to alter gene expression, without altering the positive charge of the histones
Non-coding RNAs: inhibits the transcription of mRNA and has regulatory and epigenetic functions
Small ncRNAs (siRNAs, miRNAs and piRNAs)
o Highly conserved
o Involved in transcriptional and post-transcriptional gene silencing through sequence-
specific base pairing with their targets
Long ncRNAs
o Poorly conserved
o Transcribed RNA molecules greater than 200 nucleotides
o Regulate gene expression by diverse mechanisms
Signal: indicates gene regulation in space and time
Decoy: titrate away transcription factors and other proteins from chromatin
Guide: recruitment of chromatin modifying enzymes to target genes
Scaffold: brings together multiple proteins to form ribonucleoprotein
complexes and affects histone modifications
DNA methylation:
Methyl groups (CH3) are needed and can be derived from dietary methyl donors
S-adenosylmethionine (SAM): major methyl donor in the cell
o methyl group is transferred from SAM to cytosine by
the DNA methyltransferases (DNMTs)
o When SAM donates its methyl group it converts into
S-Adenosyl homocysteine (SAH)
o SAH is consequently converted to homocysteine
(HCY), which can be converted to methionine with the
help of vitamin B12
o Methionine, together with an adenosyl molecule, will
be converted to SAM again
The addition of methyl groups to DNA is
carried out by a family of enzymes called
DNA methyltransferases (DNMTs)
o DNMT1, DNMT3a and DNMT3b
are required for establishment and
maintenance of DNA methylation
patterns
DNMT1 is responsible for
the maintenance of established patterns of DNA methylation
DNMT3a and 3b mediate establishment of new, or de novo, DNA
methylation patterns
o DNMT2 and DNMT3L also have more specialized but related functions
DNMT2 displays weak DNA methyltransferase activity but actually functions
as an RNA methyltransferase
DNMT3L has no catalytic activity but recruits DNMT3a and DNMT3b to their
targets and increases the ability of both DNMT3s to bind to methyl groups,
thus facilitating methylation
3
