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Kost, kræft og helbred En undersøgelsen til belysning af sammenhængen mellem kost og kræft
Anne Tjønneland Kim Overvad Institut for Epidemiologisk Institut for Epidemiologi og Kræftforskning Socialmedicin Kræftens Bekæmpelse Aarhus Universitet Kost, kræft og helbred
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Diet, Cancer and Health Organisation
Principal investigators Anne Tjønneland Institute of Cancer Epidemiology Danish Cancer Society Kim Overvad Department of Epidemiology and Social Medicine Aarhus University Funding Danish Cancer Society EU NCU Steering Committee Jørn Olsen (Chairman) Britmarie Sandström Per Kragh Andersen Peter Ebbesen Torben Kruse Hans Sjöström Kost, kræft og helbred
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Beskrivelse af databasen
Demografi Kost Baggrund, livsstil Antropometri/biologiske målinger Biologisk materiale Kost, kræft og helbred
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Deltagere En stikprøve af befolkningen 57.054 personer 27.179 mænd
kvinder Født i Danmark 7% af aldersgruppen år Bosiddende i Københavns kommune Frederiksberg kommune Københavns amt Århus amt Ikke tidligere haft en kræftsygdom Kost, kræft og helbred
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Kostoplysninger Kostspørgeskema
Semikvantitativt fødevare-frekvensspørgeskema Normalkost gennem det sidste år 196 spørgsmål Måltider Fødevarer Kosttilskud Fedtstoffer brugt ved madlavning Tilberedningsmetoder Kost, kræft og helbred
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Kost, kræft og helbred
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Spørgeskema om risikofaktorer
Baggrund og livsstil Spørgeskema om risikofaktorer Rygevaner Familieoplysninger - tidligere og nuværende Uddannelse Alkoholvaner Arbejde - tidligere og nuværende Kvindeoplysninger Hudtype - menstruationsforhold Fysisk aktivitet - graviditeter Sygdomme - svangerskabsforebyggelse - tidligere og nuværende - hormonbehandling Medicinindtagelse Mandeoplysninger Afføringsvaner - sterilisationsspørgsmål Vægt - antal børn - tidligere og nuværende Kost, kræft og helbred
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Diet, Cancer and Health Questionnaire check * Optically readable
* Missing marking. double marking * Limits * Logical checks Diet, Cancer and Health
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Antropometri og biologiske målinger
Ståhøjde Siddehøjde Vægt Taljemål Hoftemål Bioimpedans Blodtryk Totalkolesterol Urin blod protein sukker Kost, kræft og helbred
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Biologisk materiale Blodprøve 30 ml filterpapir
serum 4 x 1 ml plasma 6 x 1 ml buffy coat 2 x 1 ml erytrocytter 2 x 1 ml Urinprøve 4 x 1 ml Fedtbiopsi Tånegleklip Kost, kræft og helbred
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Diet, Cancer and Health Tube Box Rack Liquid nitrogen container
Kost, kræft og helbred
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Section of the biological bank
Kost, kræft og helbred
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Monitoring of the nitrogen containers
Kost, kræft og helbred
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Spare nitrogen container in case of break down
Kost, kræft og helbred
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Liquid nitrogen container
Kost, kræft og helbred
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Kost, kræft og helbred Registerkoblinger hvert år
* Det Centrale Personregister (CPR) * Cancerregisteret * Dødsårsagsregisteret * Landspatientregisteret Spørgeskemadata med 3-5 års interval * Ændringer for eksponering * Information om nye eksponeringer * Oplysninger om sygdomsudfald Kost, kræft og helbred
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Antal kræfttilfælde blandt deltagerne (primo 2003)
Mænd Kvinder Total 1713 2052 3765 Colon/rectum 241 208 Breast 5 836 Lung 234 209 Prostate 325 - Kost, kræft og helbred
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EPIC collaborating centres
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 I.A.R.C. LYON PARIS FLORENCE MILAN RAGUSA TURIN NAPLES
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Subject Recruitment in the EPIC Study
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Expected Cancer Cases in the EPIC Study after 5 and 10 Years’ Follow-up
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EPIC data on diet Two dietary measurements:
Dietary questionnaire on usual diet from all subjects Very detailed, 150 to 300 foods per questionnaire To relate diet to cancer risk One day “actual” diet from a 7% sample of subjects (32.000) Computerized, 3000 foods and 700 recipes per country To calibrate dietary measurements between countries
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EPIC Database on ORACLE system
Estimated final size of the database = 150 giga bytes. 90 screens have been developed to facilitate the transfer, standardization, control and export of the data subjects * common variables 1 Billion values to be stored
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Diet and cancer hypothesis 1: FOODS
Increased risk Meat (red?) Processed meat Salted food Sweets and sugar Reduced risk Vegetables Fruits Whole grain cereals Oily fish
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Diet and cancer hypothesis 2 :NUTRIENTS
Reduced Risk Poly Unsaturated Fats. Fibre Vitamins and minerals Various non-nutrient components Increased Risk Total fat Saturated fat (Animal) protein Sugars Cooking products
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Diet/Nutrition and cancer hypothesis 3 :
ENERGY BALANCE Increased risk Overweight Abdominal obesity Sedentary life Reduced risk Normal weight Low waist/hip ratio Physical activity
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Diet/Nutrition and cancer hypothesis 4 : Endogenous hormones
Androgens, Estrogens, Insulin, Growth Factors (IGFs) and their binding proteins
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Hypotheses 5 : GENETIC FACTORS
Focused on genetic polymorphisms, e.g. genes involved in hormones metabolism, DNA repair, carcinogens metabolisms, prostaglandins synthesis… Interactions between genes, lifestyle and environment Rare mutations in cancer associated genes (e.g. BRCA1, BRCA2, HNPCC)
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EPIC Biorepository
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EPIC BIOREPOSITORY: TUBES AND GOBLETS USED TO HOLD PLASTIC STROWS
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EPIC BIOREPOSITORY AT IARC-WHO
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EPIC BUILDING, LYON, IARC-WHO
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Total fruit consumption (grams/day) in EPIC adjusted for age, season and day of the week : MEN
500 450 u 400 350 300 grams/day 250 200 150 100 50 Murcia Ragusa Trin Umea Florence Granada Varese Oviedo Greece Malmo Pamplona Potsdam Aarhus Heidelberg Bilthoven San Sebastian Copenhagen UK - Health conscious UK: General population centres
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Variations of biomarkers of diet between EPIC cohorts
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Variations of biomarkers of diet between EPIC cohorts
Lycopene, men years 100 90 80 70 60 microg/dl 50 40 30 20 10 Murcia Umeå Florence Greece Granada Cambridge Heidelberg Potsdam Denmark Malmö Varese/Turin Oxford (*Veg) Ragusa/Naples The Netherlands Northern Spain
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Dietary patterns associated with participating countries
Country 150% or greater than mean overall intake Italy Vegetables, fruits, cereal products, vegetable oils, sauces Greece Vegetable, legumes, vegetable oils Spain Vegetables, fruits, legumes, vegetable oils, milk, eggs, fresh meat, fish France Sugars, butter, dairy products Bingham & Riboli, 2004 Kost, kræft og helbred
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Dietary patterns associated with participating countries
Country 150% or greater than mean overall intake Germany Butter, processed meat, coffee, juices The Netherlands Potatoes, margarines, dairy products, processed meat, tea, coffee United Kingdom Potatoes, cakes, sugar, margarine, butter, tea, soft drinks Denmark Sugars, margarines, tea, coffee, soft drinks, alcohol Sweden, Norway Potatoes, cakes, sugars, margarine, dairy products, coffee, soft drinks Bingham & Riboli, 2004 Kost, kræft og helbred
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Lifestyle factors and risk of breast cancer in postmenopausal 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 cases of postmenopausal breast cancer Kost, kræft og helbred
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Delprojekter i brystkræftstudiet
Kohortestudier Indtag af alkohol Indtag af frugt og grøntsager Indtag af kulhydrater/GI/GL Indtag af fisk Fysisk aktivitet Kropssammensætning Brug af hormoner i forbindelse med overgangsalderen Kost, kræft og helbred
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Delprojekter i brystkræftstudiet
Nestede case-control studier Enterolactone i plasma Oxiadation af lipider og proteiner i plasma Estrogenmetabolitter (16a-OHE1 + 2-OHE) i urin DNA-reparationsprodukter i urin IGF1+2 samt IGFBP2+3 i serum Estradiol, SHBG, estron og FSH i serum Kost, kræft og helbred
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Delprojekter i brystkræftstudiet
Nestede case-control studier, fortsat Antioxidant enzymer i røde blodlegemer Genetiske polymorfier vedr. metaboliske enzymer Genetiske polymorfier vedr. reparations enzymer Organochloriner i fedtvæv Kost, kræft og helbred
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Risikofaktorer for brystkræft (internt justerede)
IRR (95% CI) En ekstra fødsel ( ) Alder ved første fødsel (5 års stigning) 1.02 ( ) Tidligere benign brystsygdom ( ) Skolegang 7 år 8-10 år ( ) 11 år ( ) HRT Tidligere ( ) Nuværende ( ) Varighed af HRT (5 års stigning) ( ) BMI (5 kg/m2 stigning) ( ) Kost, kræft og helbred
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Frugt og grøntsager De kræftforebyggende effekter af frugt og grøntsager har været tilskrevet en række vitaminer, mineraler og andre fytokemikalier Antioxidative effekter har været i fokus Kost, kræft og helbred
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Epidemiologisk baggrund
En lang række case-kontrol studier Primære fund: beskyttende effekt 11 kohorte studier Ingen association til brystkræft Kost, kræft og helbred
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Olsen, J. Nutr. 2004 Kost, kræft og helbred
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Olsen, J. Nutr. 2004 Kost, kræft og helbred
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Olsen, J. Nutr. 2004 Kost, kræft og helbred
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Konklusion Ingen sammenhæng mellem indtag af frugt og grøntsager og risiko for brystkræft - I overensstemmelse med alle tidligere kohortestudier Måske forskellige effekter for ER+ og ER- brystkræft? Kost, kræft og helbred
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Enterolactone Enterolactone er det primære fytoøstrogen i den danske kost Enterolactone tilskrives antioxidative effekter og har været relateret til reducerende effekter vedr. tumor progression og metastaseren Forskningen er dog yderst begrænset og stammer fra in vitro og dyreeksperimentelle studier Kost, kræft og helbred
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Enterolactone Enterolactone stammer fra plantelignaner der indgår som en del af fiberkomponenten i planters cellevægge Lignanerne fermenteres i tyktarmen og optages som enterolactone Kost, kræft og helbred
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Kilder til enterolactone
Fuldkornsprodukter Grøntsager Kaffe Rygning Fedt BMI Johnsen & Hausner 2003 Kost, kræft og helbred
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Epidemiologisk baggrund
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Olsen, CEBP. 2004 Kost, kræft og helbred
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Enterolactone og brystkræft, kvartiler
Olsen, CEBP 2004 Kost, kræft og helbred
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Hvorfor reference i 2. Kvartil?
Enterolactoneniveauet afhænger af fermentering i tyktarmen Antibiotikabehandling ødelægger tarmfloraen De kvinder der er i laveste kvartil er måske en blanding af kvinder med ”sande” lave enterolactoneniveauer og kvinder med akut lave niveauer pga. nylig antibiotikabehandling Kost, kræft og helbred
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Konklusion Der er lavere incidens af brystkræft blandt kvinder med høje niveauer er enterolactone i plasma Den beskyttende effekt ses primært i forhold til ER- brystkræft Skyldes den øgede risiko for brystkræft ved langvarigt forbrug af antibiotika en nedsat produktion af enterolactone? Kost, kræft og helbred
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Hvorfor ER- brystkræft?
Hypoteser Den beskyttende effekt af enterolactone er primær antioxidativ. Effekten på ER+ bliver ”overskygget” af østrogene risikofaktorer (fra enterolactone eller andet)? ER- brystkræft er et senere stadie af ER+ brystkræft. Enterolactone ”bremser” progressionen fra ER+ til ER- brystkræft? Kost, kræft og helbred
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Hvor ofte drikker De den angivne mængde?
Alkoholoplysninger Kostspørgeskema Hvor ofte drikker De den angivne mængde? - Lys øl (flaske) - Almindelig øl (flaske) - Stærk øl (flaske) - Vin (rød, hvid,rosé) (glas) - Hedvin (ex. portvin) (genstand) - Spiritus (ex. snaps) (genstand) Angives i kategorier fra aldrig til 8 gange/dag Kost, kræft og helbred
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Alkoholoplysninger Livsstilsskema
Hvor ofte drikker De almindeligvis alkohol (øl, vin, hedvin eller spiritus)? - Aldrig - Mindre end 1 gang om måneden - 1-3 gange om måneden - 1 gang om ugen - 2-4 gange om ugen - 5-6 gange om ugen - Hver dag Kost, kræft og helbred
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Characteristics of 23,778 women in the Danish Diet, Cancer and Health cohort, 1993-2000
No. of cases = 426 (%) No. of cohort = 23,778 (%) Alcohol groups Abstainers 1 10 (2.3) 560 (2.4) Occasional drinkers 2 437 (1.8) Drinkers (grams per day) 0 to 6 122 (28.6) 7,875 (33.1) >6 to <12 89 (20.9) 5,812 (24.4) 12 to 24 93 (21.8) 4,903 (20.6) >24 to <60 3,794 (16.1) 60 9 (2.1) 357 (1.7) Kost, kræft og helbred
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Median (5-95 percentiles) Median (5-95 percentiles)
Characteristics of 23,778 women in the Danish Diet, Cancer and Health cohort, Median (5-95 percentiles) Median (5-95 percentiles) Age (years) 57 (51-64) Age at first birth (years) 23 (18-32) 23 (18-31) BMI + 24.8 ( ) 24.9 ( ) Alcohol (grams per day) * 11.5 ( ) 9.7 ( ) Alcohol from different types of beverages Wine 5.5 ( ) 5.4 ( ) Beer 1.1 (0-12.7) 1.0 (0-12.2) Spirits 0.3 (0-7.8) * Abstainers and occasional drinkers not included + Weight (kg)/height (m2) Kost, kræft og helbred
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Rate ratio for increases of 10 g alcohol per day by type of alcohol among 23,778 women in the Danish Diet, Cancer and Health cohort, Type of alcohol Adjusted* Rate ratio (95% CI) Mutually adjusted** P for similar effect Total alcohol 1.10 ( ) - Wine 1.14 ( ) 1.13 ( ) Beer 1.01 ( ) 0.98 ( ) 0.21 Spirits 1.15 ( ) 1.09 ( ) * Rate ratio were adjusted for parous/nulliparous and number of births (continuous), age at first birth (in years), benign breast tumour removed (yes/no), years at school categorized, (7, 8-10, >10), use of HRT (never, past, current), duration of HRT (in years), and BMI (continuous) ** The beverage specific estimates were in addition adjusted for each other (wine, beer, spirits) Tjønneland, CCC 2003 Kost, kræft og helbred
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Intake (g/day) (5-95% percentile)
Rate ratio* (RR) in each category of drinking pattern among 23,778 women in the Danish Diet, Cancer and Health cohort, Drinking occasions n Intake (g/day) (5-95% percentile) RR (95% CI) Every day 3,188 (12-70) 1.02 ( ) 5-6 times/week 2,471 (10-47) 0.96 ( ) 2-4 times/week 7,443 (5-32) 1 Once/week 3,467 (2-15) 0.99 ( ) Less than once/week 6,212 (0.35-8) 0.87 ( ) * Adjusted for total alcohol intake as well as for parous/nulliparous and number of births (continuous), age at first birth (in years), benign breast tumour removed (yes/no), years at school categorized, (7, 8-10, >10), use of HRT (never, past, current), duration of HRT (in years), and BMI (continuous) * Adjusted for total alcohol intake as week as well as Tjønneland, CCC 2003 Kost, kræft og helbred
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Rate ratio of breast cancer by frequency of alcohol consumption
Tjønneland, CCC 2003 Kost, kræft og helbred
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Rate ratio (RR) of breast cancer according to an increase of 10 grams of alcohol intake for different exposure periods among postmenopausal women in the “Diet, Cancer and Health” cohort, Exposure period RR 1 (95% CI) RR 2 (95% CI) Twenties 0.97 ( ) 0.97 ( ) Thirties 0.94 ( ) 0.94 ( ) Forties 1.01 ( ) 1.01 ( ) Fifties – baseline 1.11 ( ) 1.04 ( ) Cumulative intake 3 1.03 ( ) 4 0.99 ( ) Adjusted for parity, age at first birth, benign breast tumour, years of school education, HRT use, duration of HRT use, BMI, total alcohol intake in other exposure periods 2. Further adjusted for current alcohol intake 3. Cumulative intake, calculated from year 20 to baseline, excluding periods without drinking alcohol 4. Rate ratio of breast cancer according to an increase of 1 drink/day/year 1 drink-year of alcohol intake. Adjusted for the same variables as in 1) except adjustment for other exposure periods Tjønneland, J. Nutr. 2004 Kost, kræft og helbred
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Age at drinking start RR (95% CI)
Rate ratio of breast cancer per 10 g/day of alcohol intake according to age at drinking start among 21,901 postmenopausal women in the “Diet, Cancer and Health” cohort, Age at drinking start RR (95% CI) <16 0.84 ( ) 17-18 1.00 19-20 0.99 ( ) 21-25 1.06 ( ) 26-30 1.38 ( ) >30 1.01 ( ) Adjusted for parous/nulliparous, no. of births, age at first birth, benign breast tumour removed, school education, use of HRT, duration of HRT and BMI Tjønneland, J. Nutr. 2004 Kost, kræft og helbred
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- app. at the same time of 1st birth 56/3,136 1.10 (0.81-1.49)
Rate ratio of breast cancer per 10 g/day of alcohol intake according to drinking start among 21,901 postmenopausal women in the “Diet, Cancer and Health” cohort, Started drinking: Cases/ cohort RR (5-95% CI) - before 1st birth 203/11,409 1.00 - app. at the same time of 1st birth 56/3,136 1.10 ( ) - after the 1st birth 135/7,356 1.11 ( ) Rate ratios were adjusted for parous/nullliparous, no. of births, age at first birth, benign breast tumour removed, years at school, use of HRT, duration of HRT, and BMI; current alcohol intake and mutually adjusted Tjønneland, J. Nutr. 2004 Kost, kræft og helbred
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Incidence Rate Ratio 1 of breast cancer per each additional 10 g/d of average daily alcohol intake according to categories for cumulative average intake of total folate among 388 cases and 388 controls, nested in the Danish “Diet, Cancer and Health” cohort Median Total folate intake 5-95% percentiles Unit 300 < 400 P for interaction Alcohol intake 11.0 ( ) 10 g 1.21 ( ) 1.12 ( ) 1.02 ( ) 1.03 ( ) 0.48 1 Adjusted for vitamin C (food-frequency questionnaire and supplements), school education (low, median, high), body mass index (linear), parous/nulliparous and number of births (linear), age at birth of first child (linear), history of benign breast tumour surgery (yes/no). Tjønneland,subm 2004 Kost, kræft og helbred
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Incidence Rare Ratio of breast cancer by total folate and alcohol intake among 388 cases and 388 controls, nested in the Danish “Diet, Cancer and Health” cohort. The reference group for all comparisons was women who consumed 300 mcg/d or less total folate and 15 g/d or less alcohol. The Incidence Rate Ratio was adjusted for vitamin C, school education (low, median, high), body mass index (linear), parous/nulliparous and number of births (linear), age at first child (linear), history of benign breast tumor surgery (yes/no). Kost, kræft og helbred
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Konklusion Alkoholindtagelse øger risikoen for brystkræft med 10% for hver gang indtagelsen øges med 10 g/dag Drikkemønsteret har ikke betydning for risikoen Tidlig drikkestart øger ikke risikoen for brystkræft blandt postmenopausale kvinder Kost, kræft og helbred
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