Nutrition and Cancer
Dr. Angela Chalé
School of Life Sciences, Pharmacy & Chemistry
LS7008
2023/24
Lecture aims and objectives
• To discuss if cancer is a disease of gene expression. Is it all about
our genes?
• We will examine the impact of environmental factors
• To discuss the role of diet and nutrition
• What evidence is considered and how?
• To explore one area:
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Red and processed meat and colorectal cancer
Evidence
Proposed mechanisms of action
Controversy
• To examine the application of functional foods in cancer
• Curcumin in experimental trials
‘Cancer is a disease of gene expression’
Wiseman (2008)
http://dx.doi.org/doi:10.1017/S002966510800712X
Endogenous
factors
Exogenous
factors
So is cancer all about your genes?
Global Cancer Incidence/Prevalence/Mortality
• http://gco.iarc.fr/
• Cancer today (2020) – see next slide (incidence)
• Cancer tomorrow (2020-2040)
Migrant (ecological) Studies: examine relationship
between environmental factors and disease outcomes
Yavari P. et al., 2006, Asian Pacific J Cancer Prev, 7, 86-90.
Inherited Mutations and Colorectal Cancer
Familial Adenomatous Polyposis (FAP)
Familial Adenomatous Polyposis (FAP)
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Autosomal dominant disease
Germline mutation in adenomatous polyposis coli (APC) gene
25-30% have no genetic basis
Hundreds to thousands of colorectal adenomas
Progression to colorectal cancer high if not identified
and treated early
• Characterised by rectal bleeding, anemia, change in
bowel habits, abdominal pain, weight loss and palpable masses,
extraintestinal manifestations (e.g., dental abnormalities),
extracolonic cancers
Half E et al., 2009 Orphanet J Rare Dis; 4:22
Familial Adenomatous Polyposis
Half E et al., 2009 Orphanet J Rare Dis; 4:22
Familial Adenomatous Polyposis
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APC is a tumor suppressor gene
Found on chromosome 5, band q21 (5q21)
Key role in Wnt signaling –regulates degradation of 𝛃-catenin
Wnt stabilizes complex containing 𝛃-catenin, conductin and glycogen
synthase kinase 3
• APC absence (colon cancers) leads to expression of 𝛃-catenin
target genes e.g., myc that further leads to expression of polyamine
ornithine decarbocylase, a proto-oncogene
Half E et al., 2009 Orphanet J Rare Dis; 4:22
Half E et al., 2009 Orphanet J Rare Dis; 4:22
Olkinuora AP et al., 2021
Olkinuora AP et al., 2021
Olkinuora AP et al., 2021
Olkinuora AP et al., 2021
Olkinuora AP et al., 2021
Olkinuora AP et al., 2021
Environment has a role to play
What is the role of diet and nutrition?
https://www.wcrf.org/dieta
ndcancer/do-not-usesupplements-for-cancerprevention/
Professor Martin Wiseman
World Cancer Research Fund International
How is the evidence assessed?
An initial interview about the Third expert Report (2018), a
comprehensive analysis of the body of research available sine 1997.
Red and processed meat and colorectal
cancer
What do the expert say about the consumption
of red and processed meat
• https://www.wcrf.org/dietandcancer/exposures/meat-fish-dairy
• https://www.wcrf.org/sites/default/files/Meat-Fish-and-Dairyproducts.pdf (pp. 5-9)
• In summary:
There is strong evidence that consuming:
üred meat increases the risk of colorectal cancer
üprocessed meat increases the risk of colorectal cancer
What is the nature of this strong evidence?
https://www.wcrf.org/sites/default/files/Meat-Fish-and-Dairy-products.pdf (p. 9)
The Continuous Update Project (CUP) Panel concluded:
ü Strong evidence that “consumption of processed meat is a convincing cause of
colorectal cancer.”
ü Strong evidence that “consumption of red meat is probably a cause of
colorectal cancer.”
Let us look at some of the evidence
https://www.wcrf.org/sites/default/files/Meat-Fish-and-Dairyproducts.pdf pp27-35
Relative risk: ratio of risk of event
among people exposed to a factor compared
to that of unexposed
Link
“When stratified by geographic location, a
significant increased risk was observed in
Europe (RR 1.23 [95% CI 1.08–1.41], but not
North America or Asia; see CUP colorectal
cancer SLR 2016, Figure 128). When stratified
by cancer type, a significant increased risk
was observed for colon cancer (RR 1.22 [95%
CI 1.06–1.39]; see CUP colorectal cancer SLR
2016, Figure 132), but not rectal cancer”.
“A separate dose–response meta-analysis of
15 studies showed a statistically significant
12 per cent increased risk of colorectal cancer
per 100 grams increase in red and processed
meat consumed per day (RR 1.12 [95% CI
1.04–1.21]; n = 31,551 cases; see CUP
colorectal cancer SLR 2016, Figure 83)”.
Limited –
suggestive:
Increases risk due
to too few studies
Red and processed meat and colorectal cancer
What is the mechanism of action?
• Diet, nutrition and
physical activity, other
environmental
exposures and host
factors interact to
affect the cancer
process
dietandcancerreport.org
• Hallmarks of cancer and two enabling characteristics
Adapted from: Cell 144,
Hanahan D and Weinberg
RA, Hallmarks of cancer:
the next generation, 646–
74, Copyright (2011), with
permission from Elsevier.
Definitions/explanations
are provided below:
https://www.wcrf.org/sites/default/
files/The-cancer-process.pdf
30-33
Glossary https://www.wcrf.org/dietandcanc
er/glossary
CONTACT COPYRIGHT
OWNER FOR
PERMISSION TO REUSE
FOR ANYTHING OTHER
THAN TEACHING AND
PERSONAL PURPOSES
dietandcancerreport.org
https://scienceblog.cancerresearchuk.org/2015/10/26/
processed-meat-and-cancer-what-you-need-to-know/
https://doi.org/10.1186/s13027-018-0174-9
https://doi.org/10.1016/j.meatsci.2014.02.011
Action of haem (heme)
https://doi.org/10.1186/s13027-018-0174-9
Carcinogenicity Nitrosamines – a group of
N-Nitroso compounds
https://doi.org/10.1186/s13027-018-0174-9
MDA Malondialdehyde
4-HNE 4-hydroxynonenal
Action of haem (heme) and N-Nitroso
Compounds – more detail
https://doi.org/10.1158/1940-6207.CAPR-10-0113
Other compounds
PAHs require activation by cytochrome
P450 (CYP) family of enzymes
Polycyclic aromatic hydrocarbons (PAHs)
http://iverson.cm.utexas.edu/courses/310N/MOTD%20Fl05/MOTDfl02%20copy/Be
nzpyrene.html
Other compounds: heterocyclic amines (HCAs)
https://doi.org/10.1111/j.1349-7006.2004.tb03205.x
https://doi.org/10.1093/toxsci/kft077
SULT – sulphotransferase
NAT- N-acetyltransferase
UGT – UDP-glucuronosyltransferase
PHAs, HCAs, NOCs
Put it all together
https://doi.org/10.1186/s13027-018-0174-9
Very recent controversy
• September/October 2019
• Uproar after research claims red meat poses no health risk
Guardian, September 2019
What did the controversial study conclude?
• Unprocessed red meat and processed meat consumption dietary guideline recommendations from the NutriRECS
consortium
• Reduction of red and processed meat intake and cancer
mortality and incidence
• Patterns of Red and Processed Meat Consumption and Risk for
cardiometabolic and Cancer outcomes - A systematic Review and
Meta-analysis of Cohort Studies
• Red and Processed Meat Consumption and Risk for All-cause
mortality and cardiometabolic Outcomees - A Systematic Review and
Meta-analysis of Cohort Studies
• Meat consumption and health - food for thought
Controversy Continues …
Link
https://www.evidencebasednutrition.org/nutritional-recommendations
Functional foods and cancer
Functional Foods
• What are they?
• Birthplace of functional foods - Japan
• Foods for Specified Health Use (FOSHU)
• European Commission Concerted Action on Functional Food Science in
Europe (FUFOSE) – consensus document
• http://journals.cambridge.org/abstract_S0007114599000471
• Page S6; section 1.5.1
Functional Foods and Cancer
Benninghoff et al. 2015 Journal of Developments in Sustainable Agriculture; 10: 34-54.
Benninghoff et al. 2015 Journal of Developments in Sustainable Agriculture 10: 34-54.
Benninghoff et al. (2015) Journal of Developments in Sustainable Agriculture 10: 34-54.
Aghajanpour et al. 2017 Am J Cancer Res; 7:740-759.
Further Reading
Further Reading
Link or via:
KU Library > Databases >
New Scientist > Videos >
search: nutrition & cancer
Questions?
Class Activity
What are some possible explanations for not finding
a difference in the number or size of polyps following
12 months of treatment with 3g/d of curcumin?
Some Possible Explanations
• Dose given
• Other investigations have used higher amounts (e.g., Carroll et al., Cancer
Prev Res [Phila] 2011, 4:354-64; used 4g/d)
• Poor bioavailability
• Did not assess absorption
• Would be important in a trial using pure curcumin particularly since their aim was to
“test the ability of the agent alone to regress adenomas” (p.6)
• Administer with fat
• Curcumin is lipophilic, complexes with fats enhancing its bioavailability
• Other natural agents
• Administer with piperine – gives black pepper its pungency
• Synergises with resveratrol
• Others – review Cas and Ghidoni, Nutrients 2019, 11, 2147