On the relationships between genes, diet and cancer - challenges and opportunities to study their link

1. Diet, genes and
cancer
Prof. Dr. Koen Kas
European Cancer Prevention Meeting - Alba, Italy
November 25, 2011
01/12/2011 1

2. Outline
 Literature and stories
 Two ‘missing links’
 New ways to study relationship
 Conclusions
Koen Kas 2

3. Insight from literature on the topic
# PubMed # Google
Genes & cancer 152.300 X 500 71.600.000
Diet & genes 8.150 24.900.000
Diet & cancer 29.600 X 10.000 302.000.000
Diet, genes & cancer 1.370 14.200.000
Search October 23, 2011
Koen Kas 3

4. Insight from literature on the topic
# PubMed # Google
Genes & cancer X5 152.300 71.600.000 : 5
Diet & genes 8.150 24.900.000
Diet & cancer 29.600 302.000.000
Diet, genes & cancer 1.370 14.200.000
Search October 23, 2011
Koen Kas 4

5. The classic stories
 Change in dietetic habits when people migrate to other
countries
 Incidence of colorectal cancer and breast cancer
 Increases 3-6 times when the Japanese migrate to Hawai
Koen Kas 5

6. Some classic players
Koen Kas 6

7. Centenarians now constitute the fastest-growing
age group owing to advances in health care
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8. Koen Kas 8

9. Defence mechanisms to be influenced by diet
 Minimise damage
 Inhibition oxidative reactions by free radical scavenging
 Detoxification of potential mutagens
 Repair damage
 Remove damaged cells (apoptosis)
Koen Kas 9

10. Genes & cancer
10 years into the ‘human genome’, function of 40% of our
21.000 genes is still a mystery – 400+ drive cancer directly
Koen Kas 10

11. Diet & genes (nutrigenetic effects)
Genetic polymorphisms alter response to dietary components
by influencing absorption, metabolism, or site of action
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12. Diet & cancer
Not possible to mimic ‘immediate’ effects of artificial genetic
mutations (KO mice, silencing vectors) for food components
Koen Kas 12

13. Diet, genes & cancer
So how do we overcome sample size and outcome issues ?
Koen Kas 13

14. Why so difficult to create ‘strong’ data ?
 Lack of robust surrogate endpoints
 cf. cholesterol – cardiovasc. diseases, glucose tolerance - diabetes
 Starts changing with the appearance of biomarkers for cancer risk
 Requires large prospective cohort studies (for observation)
 European Prospective Investigation into Cancer and Nutrition (EPIC)
 To include adjustments for confounding factors
 Intervention studies required to prove causality
 Including prospective genotyping
Koen Kas 14

15. Enter epigenetics
Koen Kas 15

16. Epigenetics
 Study of heritable changes in gene expression caused by
mechanisms other than changes in the underlying DNA
sequence
 DNA methylation and histone deacetylation serve to
suppress gene expression without altering their sequence
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17. The epigenetic code
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18. Epigenetics, II
 Changes remain through cell divisions for remainder of
cell's life and may last for multiple generations
 NO change in the underlying DNA sequence
 Allows to study how genes react to environmental and
dietary influences
 Certain genes that help prevent cancer turned off with
certain foods while other foods turn on genes to fight cancer
Koen Kas 18

19. Enter the microbiome
 > our 400 billion cells
 > our 21.000 genes
 Transferring the microbes
from obese mouse to a lean
mouse results in weight
gain for the recipient
 Could ‘modification of’
intestinal flora influence
health / disease ?
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20. How to overcome conceptual and
practical challenges ?
 New technologies to the rescue
 Next Gen (deep) Sequencing
 Social networks
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21. Decoding the human genome …
2001-2003
Database of known and hypothetical genes
/ proteins from mix of individuals
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22. … initiated the future of medicine (public
perception)
Medicine tailored to the
patient (Personalised)
“DNA-based” diagnostics:
the birth of biomarkers
First routinely used
biomarkers are indeed
specific DNA mutations
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23. The tip of the iceberg
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24. But what was / is the real impact ?
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25. Koen Kas 25

26. Koen Kas 26

27. Next generation nucleotide sequencing (NGS)
Towards the 100(0)$ genome
in a few hours
Deep sequencing of
3.000.000.000 nucleotides
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28. Consumer diagnostics companies
Empower individuals with real-time info medical risks
 23andme
 Navigenics
 DecodeMe
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29. Build on ‘Patient’ awareness Social network
Will lead to web-based self diagnosis
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30. The potential of 700 million people connected
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31. Consumer Apps diet
The Eatery (Massive Health)
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32. 4
Koen Kas 33

33. Genes VERSUS diet -> 1. Genes AND diet
Cancer Cancer
Cancer
Genes Diet
Genes Diet
Diet Genes
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34. 2. Diet does not change structure, but how
genes are expressed (Epigenetics)
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35. 3. Our microbiome an important new determinant
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36. 4. Power to perform decent studies to unravel link
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37. Contact information
Prof. Dr. Koen Kas
Professor University Ghent, Belgium
Chief Executive Officer, InBioVeritas
E koen.kas@inbioveritas.com
W http://inbioveritas.com/
L be.linkedin.com/in/koenkas
T @kaskoen
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