The Malmö Diet Cancer StudyPeter M Nilsson, MD, PhD, Professor

Dept. Clinical Sciences, LUClinical Research UnitDept. Internal Medicine

Skane University Hospital, Malmö

FAIR Data Seminar5th February 2019

Malmö Diet Cancer Study – baseline 1991 to 1996

The European Prospective Investigation into Cancer and Nutrition (EPIC) study

The Malmo Diet Cancer Study

• 30,000 subjects examined in 1992-1996, of which28,000 subjects had full data set (diet) – EPIC cohort

• Physical exam, questionnaire, dietary registration• Biobank samples, DNA• Genetics: GWAS, exome sequencing in all (Regeneron

Inc. US)• Register follow-up for incident cardiometabolic and

cancer events until 2016-12-31• Supported by the Research Council of Sweden as a

national infrastructure for research

MALMÖ KOST CANCER STUDIEN: 1991 - 1996

DESIGN OCH METODER:

• Populationsbaserat screening program (individer födda 1923-1950, boende i Malmö)

• Material: 28,449 individer(17,203 kvinnor (60%), 11,246 män)

• Baselinje undersökning:Självadministrerat frågeformulär, kroppsundersökning, kost (inkl intervjuv), biobank

CV kohort (n=6,103): karotid ultraljud och fastande laboratorie tester

• Deltagarfrekvens: 41 %

• Icke deltagande: Högre dödlighet men lägre cancer incidens innan baslinjen, lägre självrapporterad god hälsa, etc

M-ålder: 59 år M-ålder: 57 år

Manjer J, et al. Eur J Cancer Prev 2001;10:489-99

Procent

Göran Berglund Bo Hedblad Elisabet Wirfält Sven-Olof IsacssonLars Janzon

Gunnar Engström Sölve Elmståhl Marju Orho-Melander Olle Melander Peter M Nilsson

Jonas Manjer

MDCS1991-2019scientists

Karin Jirström Jan Nilsson Emily Sonestedt Margaretha Persson

The Malmo Diet Cancer CV cohort

• 6100 subjects examined in 1992-1996• 3700 subjects (mean age 71 years, 2/3 women)

examined during the MDC-CV re-exam in 2007-2012• Pulse Wave Velocity (PWV) in 3050 subjects

(SphygmoCor) – arterial stiffness• Biobank samples, DNA, OGTT in non-DM subjects• Genetics: GWAS, exome sequencing in all (Regeneron

Inc. US; PI: Olle Melander)• Register follow-up for incident events• Supported by the Research Council of Sweden

B-mode Carotid Artery Ultrasound Examination

B-mode ultrasound quantification and qualification of carotid atherosclerosis

Externalcarotid

Bifurcation Common carotid

Plaque

Internalcarotid IMT

10 mm long segment

Gerd Östling 1998

Carotid-femoral Pulse Wave Velocity (c-f PWV) measured by SphygmoCor®

Femoral artery

Carotid artery

PWV=∆L/∆t

Laurent, S. et al. Eur Heart J 2006 2006 27:2588-2605.

Research on arterial stiffness in MDC

MALMÖ DIET CANCER STUDY: 1991 - 1996

ENDPOINT REGISTERS

• SOCIALSTYRELSEN – Total- an cause-specific mortality– National in-patient register– Cancer register

• Local MI and stroke register (STROMA)

31 December 2016 (600.000 person-years):- 9827 deaths (3220 cvd, 3613 cancer)- 3864 Cardiac Events: MI, sudden cardiac death- 3353 stroke- 2070 congestive heart failure, hospital-treated- 4284 diabetes- 10 764 cancer (1344 breast cancer)

Anders Dahlin, data manager 2019

Clinical dataeg. treatment

Imaging e.g. breast density

SNP:s700.000

Tumour characteristics

e.g. type, grade, and hormone receptors

MDCSBreast cancer

ready available data

Jonas ManjerKarin Jirström

The Malmo Offspring Study cohort• Ongoing since March 2013, planned until 2020• Children and grand-children to index subjects

(grandparents) in the MDC-CV cohort• At present 3600 subjects screened for PWV

(SphygmoCor), but also 24-h Arteriograph, 24-h ABPM• Focus on phenotyping, genetics, diet, oral and GI

microbiota patterns (PI: Marju Orho-Melander)• Additional vascular and metabolic phenotypes: carotid

ultrasound, EndoPat, AGE Reader (sf), biomarkers• Supported by the Research Council of Sweden, and HLF

MOS methods• Physical examination• Questionnaire• Lab-samples (with DNA extraction)• Urinary- and feces sampling (microbiota)• OGTT (in the beginning), changed to fasting samples• Technical investigations (PWV, PWA, cIMT, EndoPat)• Dietary registration (4-day)• Cognitive testing• Oral and dental investigations, oral microbiota in the

Malmö Offspring Dental Study (MODS)ti

PI: Peter M Nilsson

Tremaroli, BäckhedNature 2012; 489:242–249

Microbiota andits consequencesfor health

- Metabolism- Obesity- Immunology- Vascular function

A link to early lifecolonization of the GItract of newbornsduring delivery

The Malmo OffspringStudy (MOS)

4-day dietary data- Louise Brunkwall- Ulrika Knutsson

Gut microbiotasalivary microbiota- PI: M Orho-Melander- Daniel Jönsson

Metabolic and vascular phenotypes- Peter M Nilsson- Olle Melander- Gunnar Engström- Margaretha Persson

Women n=476

Controls n= 345 Breast cancerCases n= 135

Men n=3,671

P Cancer at time of selection n= 691

P Cancer free at time of selection n=2,980

Malmö Birth Data Cohort, n=4,309

MDC n=476

MPP n=165

MPPn=3,351

MDCn=2,353

Nilsson PM, Johnson L 2018

MDC

Data on birth weight and gestational age

Summary

• The Malmö Diet Cancer (MDC) is a big cohort(n= 28,000) 1991-1996 with a smaller Cardiovasculararm, CVA (n= 6000), for long-term follow-up of incident events such as mortality, cancer, diabetes, and CVD, etc. trough national and regional register linkages

• The MKC CVA Re-exam study 2007-2012 (n= 3700) focused on arterial stiffness, vascular ageing and impaired glucose metabolism/diabetes

• We have rich resources of data, biobank samples, DNA• In the ongoing Malmö Offspring Study (MOS) children

and grandchildren to index individuals in MDC areexamined during 2013 to 2020, aiming for 6000 subjects

PN2019