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Summary of HNH-37806 Nutrition and Cancer

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This is a summary of all the lectures and knowledge clips that are given during the course Nutrition and Cancer (HNH-37806) that are needed for the examining.

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  • 18 oktober 2021
  • 22
  • 2021/2022
  • Samenvatting
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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

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, 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


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,  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




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