NCU conference Nutrition, Cancer and Biobanks the lessons learnt

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NCU conference Nutrition, Cancer and
Biobanks- the lessons learnt

• Anne Tjønneland
• Institute of Cancer Epidemiology
• Danish Cancer Society
• 30 August 2005

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• The advantage of including biological material in
  epidemiologic studies on nutrition and cancer

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• Presentation of the biobank in the Danish
  Diet, Cancer and Health study
• The EPIC study
• Examples of the use of the biobank in conducted
  studies
• Conclusion

• Diet, Cancer and Health

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Diet, Cancer and Health
Study Population Study area Copenhagen and
Aarhus Participants Random sample of the
generel population, 1993-1997 57,053 men
and women 50 - 64 years 7 No previous
cancer diseases Born in Denmark

• Diet, Cancer and Health

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Diet, Cancer and Health

• Exposure information
• Dietary questionnaire
• Lifestyle questionnaire
• Anthropometric measurements
• Biological material

• Diet, Cancer and Health

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Diet, Cancer and Health

• Biological material
• Blood 30 ml Urine 4 x 1 ml
• - serum 4 x 1 ml Adipose tissue (app. 50 mg)
• - plasma 6 x 1 ml Toe nail clippings
• - buffy coat 2 x 1 ml
• erythrocytes 2 x 1 ml
• - whole blood on filter paper
• Storage in nitrogen vapour (max. -1500 C)

• Diet, Cancer and Health

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Section of the biological bank

• Diet, Cancer and Health

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Liquid nitrogen container

• Diet, Cancer and Health

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Spare nitrogen container in case of break down

• Diet, Cancer and Health

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• Diet, Cancer and Health

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Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Fig. 1 Schematic overview of the Diet, Cancer and
Health study Study base 57,054 persons men
and women 50-64 years at enrolment  
Central Population Register
Central Population Register
Central Population Register
Central Population Register
Central Population Register
Central Population Register
Central Population Register
Central Population Register
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Danish Cancer RegistryFollow-up 6.5 years per
31-12-2002

• Diet, Cancer and Health

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Cancer incidents among participants (primo 2003)

• Diet, Cancer and Health

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Lifestyle factors and risk of breast cancer in
postmenopausal women
29,875 women
326 prevalent cancers 55 missing
information (alcohol) 4,844 premenopausal
24,650 postmenopausal
872 excluded due to missing information on
co-factors
23,778
Follow up 31 December 2000- 425 cases of
postmenopausal breast cancer

• Diet, Cancer and Health

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Breast Cancer StudyProject plans

• Explore further aspects of known risk factors
• Explore possible risk factors
• Go deeper into known and possible risk factors by
  using biological samples to study
• Dietary exposure levels
• Gene-diet interactions
• Exposure levels of endogenous factors

• Diet, Cancer and Health

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Subprojects in the breast cancer study
Cohort studies Alcohol intake Fruit and
vegetable intake Carbohydrate/GI/GL intake
Fish intake Physical activity Body
composition Use of hormones in relation to
menopause

• Diet, Cancer and Health

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Subprojects in the breast cancer study
Nested case-control studies Enterolactone in
plasma Oxidation of lipids and proteins in
plasma Oestrogen metabolites (16a-OHE1 2-OHE)
in urine DNA- adducts in urine IGF12 and
IGFBP23 in serum Estradiol, SHBG, estrone and
FSH in serum

• Diet, Cancer and Health

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Sub-projects in the breast cancer study
Nested case-control studies, continued Antioxidan
t enzymes in red blood cells Genetic
polymorphisms regarding metabolic
enzymes Genetic polymorphisms regarding
reparation enzymes Organochlorines in fat
tissue

• Diet, Cancer and Health

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Risk factors for breast cancer (mutually adjusted)
IRR (95 CI) One extra birth 0.87
(0.77-1.00) Age at first birth (5 years
increase) 1.02 (0.89-1.16) History of benign
breast tumour surgery 1.65 (1.30-2.09) School
education ? 7 years 1 8-10
years 1.00 (0.80-1.26) ? 11 years 1.35
(1.02-1.79) HRT Previously 1.10
(0.80-1.51) Present 1.97 (1.50-2.58) Duration
of HRT (5 years increase) 1.07 (0.97-1.19) BMI (5
kg/m2 increase) 1.07 (0.96-1.20)

• Diet, Cancer and Health

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Enterolactone
Enterolactone is the primary phytooestrogen in
the Danish food Enterolactone is ascribed to
antioxidative effects and has been related to
reducing effects regarding tumour progression and
progression of metastases However, research is
extremely limited and is mainly limited to in
vitro and animal experimental studies

• Diet, Cancer and Health

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Enterolactone
Enterolactone is ascribed to plant lignans as a
part of the fibre component in the cell wall of
the plant The lignans ferment in the colon and
digest as enterolactone

• Diet, Cancer and Health

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Sources of enterolactone
Whole grain products ? ? Vegetables ? Coffee
? Smoking ? ? Fat ? ? BMI ?
Johnsen Hausner 2003

• Diet, Cancer and Health

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Olsen, CEBP. 2004

• Diet, Cancer and Health

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Meat intake and Breast Cancer Risk

• Questionnaire data
• Total meat
• Red meat
• Genotyping of DNA
• NAT1 Slow/Fast
• NAT2 Slow/Intermediate Fast

• Diet, Cancer and Health

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Egeberg, 2005 Master Thesis

• Diet, Cancer and Health

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Egeberg, 2005 Master Thesis

• Diet, Cancer and Health

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Adipose organochlorine concentrations and risk
of breast cancer

• Nested case-control study (n816)
• Measured 14 pesticides and 18 polychlornated
  biphenyles in adipose tissue
• Conclusion Results do not support that
  higher organochlorine body levels
  increase the risk of breast cancer
• Raaschou-Nielsen, CEBP 2005

• Diet, Cancer and Health

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Adipose organochlorine concentrations and risk
of breast cancer

• Diet, Cancer and Health

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UK OXFORD CAMBRIDGE NETHERLANDS
UTRECHT RIVM GERMANY POTSDAM
HEIDELBERG FRANCE PARIS ITALY TURIN
MILAN FLORENCE NAPLES RAGUSA SPAIN
OVIEDO SAN SEBASTIAN PAMPLONA
MURCIA GRANADA GREECE ATHENS SWEDEN
UMEA MALMO DENMARK AARHUS
COPENHAGEN NORWAY TROMSO
EPIC collaborating centres
COPENHAGEN
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Variations of biomarkers of diet between EPIC
cohorts

• Diet, Cancer and Health

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Variations of biomarkers of diet between EPIC
cohorts
Lycopene, men 45-64 years
100
90
80
70
60
microg/dl
50
40
30
20
10
0
Umeå
Murcia
Malmö
Greece
Florence
Granada
Potsdam
Denmark
Heidelberg
Cambridge
Varese/Turin
Oxford (Veg)
Northern Spain
Ragusa/Naples
The Netherlands

• Diet, Cancer and Health

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Serum sex steroids in premenopausal women and
breast cancer risk in EPIC

• Diet, Cancer and Health

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Conclusions

• The lesson learnt
• Samples can successfully be stored, retrieved and
  used after several years of storage
• Biological samples are an important, necessary
  aspect to include in studies on diet, nutrition,
  hormones and cancer

• Diet, Cancer and Health

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Conclusions

• Biomarkers of diet (fatty acids, lycopene,
  enterolactone)
• Genetic markers of susceptibility (NAT) and
  gene-diet interaction
• Diet related risk factors (enterolactone)
• Other risk factors(organochlorines, endogenuous
  hormones)

• Diet, Cancer and Health

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Conclusions

• We shall balance lifestyle and genomics in
  research for disease prevention.
• Overly expectations regarding the benefits of
  genetic research have the potential to distort
  research priorities and spending for health.

• Diet, Cancer and Health

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• Conclusions from migrant and twin studies show
  that the large majority of cancers in Western
  populations are due to environmental rather than
  genetic factors.
• Genetic contribution is mostly accounted by a
  large number of polymorphisms

• Diet, Cancer and Health

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• Identifying persons who are genetically more
  susceptible to the effects of smoking is a
  distraction from effects to avoid smoking in the
  whole population.
• - But genomic research in epidemiologic
  studies of environmental factors could
  provide additional insight knowledge on
  causality and health benefits

• Diet, Cancer and Health