Kost, kræft og helbred

En undersøgelsen til belysning af sammenhængen mellem kost og kræft

Anne Tjønneland Kim Overvad

Institut for Epidemiologisk Institut for Epidemiologi ogKræftforskning Socialmedicin

Kræftens Bekæmpelse Aarhus Universitet

Diet, Cancer and Health

Organisation

Principal investigatorsAnne TjønnelandInstitute of Cancer EpidemiologyDanish Cancer Society

Kim OvervadDepartment of Epidemiology and Social MedicineAarhus University

FundingDanish Cancer SocietyEUNCU

Steering CommitteeJørn Olsen (Chairman)Britmarie SandströmPer Kragh AndersenPeter EbbesenTorben KruseHans Sjöström

Beskrivelse af databasen

Demografi

Kost

Baggrund, livsstil

Antropometri/biologiske målinger

Biologisk materiale

En stikprøve af befolkningen• 57.054 personer

27.179 mænd

29.875 kvinder

• Født i Danmark

• 7% af aldersgruppen 50-64 år

• Bosiddende i

Københavns kommune

Frederiksberg kommune

Københavns amt

Århus amt

• Ikke tidligere haft en kræftsygdom

Deltagere

Kostspørgeskema• Semikvantitativt

fødevare-frekvensspørgeskema

• Normalkost gennem det sidste år

196 spørgsmål• Måltider• Fødevarer• Kosttilskud• Fedtstoffer brugt ved

madlavning• Tilberedningsmetode

r

Kostoplysninger

Brød og fedtstof på brød Hvor mange skiver brød spiser De? Når De svarer på spørgsmålene, skal De tænke på brød til alle måltider. Et halvt rundstykke, en halv bolle eller et stykke flûte svarer til en skive franskbrød.

pr. måned pr. uge pr. dag Brød aldrig/

sjældent 1 2-3

1-2 3-4 5-6

8 eller 1 2-3 4-5 6-7 flere

Rugbrød (antal ½ skiver)

Lyst franskbrød (antal hele skiver)

Groft franskbrød (antal hele skiver)

Knækbrød (antal hele skiver)

Hvor mange skiver brød kommer De fedtstof på? (Nogle bruger kun fedtstof en gang imellem).

pr. måned pr. uge pr. dag Fedtstof på brød aldrig/

sjældent 1 2-3

1-2 3-4 5-6

8 eller 1 2-3 4-5 6-7 flere

Rugbrød med fedtstof (antal ½ skiver)

Lyst franskbrød med fedtstof (antal hele skiver)

Groft franskbrød med fedtstof (antal hele skiver)

Knækbrød med fedtstof (antal hele skiver)

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

Diet, Cancer and Health

Questionnaire check

* Optically readable* Missing marking. double marking* Limits* Logical checks

Antropometri og biologiske målinger

Ståhøjde

Siddehøjde Vægt Taljemål Hoftemål Bioimpedans Blodtryk Totalkolesterol Urin

blod protein sukker

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

Diet, Cancer and Health

Tube

Rack

Liquid nitrogen container

Box

Section of the biological bank

Monitoring of the nitrogen containers

Spare nitrogen container in case of break down

Liquid nitrogen container

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

Antal kræfttilfælde blandt deltagerne(primo 2003)

Mænd Kvinder Total

Total 1713 2052 3765

Colon/rectum

241 208

Breast 5 836

Lung 234 209

Prostate 325 -

I.A.R.C.LYON

PARIS

FLORENCE

MILAN

RAGUSA

TURIN

NAPLES

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

Subject Recruitment in the EPIC Study

Subjects included End of subject recruitment

Questionnaire Blood

Spain 41 529 40 040 1996

I taly 47 822 47 822 1998

UK 76 041 40 901 1998

Netherlands 40 659 36 924 1998

France 72 000 24 000 1993

Germany 55 000 53 000 1998

Greece 24 200 24 104 1999

Sweden 57 932 62 122 1996

Denmark 57 100 56 800 1997

Total 9 countries 472 283 385713

Expected Cancer Cases in the EPIC Study

after 5 and 10 Years’ Follow-up Cancer

M e n 5 years 10 years

W o m e n 5years 10 years

Stomach 268 639 195 483 Colorectum 530 1241 731 1748 Colon 305 719 466 1120 Rectum 225 522 265 628 Pancreas 143 333 132 323 Larynx 133 297 24 52 Lung 1037 2423 394 866 Bladder 289 701 105 256 Kidney 124 280 127 293 Prostate 447 1156 - - Breast - - 2156 4477 Cervix - - 283 582 Uterus - - 472 1054 Ovary - - 389 833 All cancers 4069 9480 6323 13979

Two dietary measurements: Dietary questionnaire on usual diet from all 470.000 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

EPIC data on diet

• Estimated final size of the database = 150 giga bytes.

• 90 screens havebeen developed tofacilitate thetransfer, standardization,control andexportof the data

• 500.000 subjects * 2000 common variables

1 Billion values to be stored

EPIC Database on ORACLE system

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

Diet and cancer hypothesis

2 :NUTRIENTS

Increased Risk• Total fat• Saturated fat• (Animal) protein• Sugars• Cooking products

Reduced Risk• Poly Unsaturated

Fats.• Fibre• Vitamins and

minerals• Various non-nutrient

components

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

Diet/Nutrition and cancer hypothesis 4 :

Endogenous hormones

• Androgens, • Estrogens,• Insulin, • Growth Factors (IGFs)

– and their binding proteins

• 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)

Hypotheses 5 : GENETIC FACTORS

EPIC Biorepository

Country No. of subjects No. of aliquots

France 20,749 290,486

Italy 47,726 668,164

Spain 39,963 559,482

United Kingdom 43,273 605,822

Netherlands 36,320 508,480

Greece 28,560 399,840

Germany 50,700 709,800

Total at IARC 267,291 3,742,074

Samples stored only at the EPIC collaborating centres

Sweden 53,785

Denmark 56,131

Total EPIC 377,207

EPIC BIOREPOSITORY: TUBES AND GOBLETS USED TO HOLD PLASTIC STROWS

EPIC BIOREPOSITORY AT IARC-WHO

EPIC BUILDING, LYON, IARC-WHO

u

Total fruit consumption (grams/day) in EPIC adjusted for age, season and day of the week : MEN

0

50

100

150

200

250

300

350

400

450

500

Mur

cia

Ragus

aTr

in

Flor

ence

San

Seba

stia

n

Grana

da

Vares

e

Ovi

edo

Pam

plon

a

Greec

e

UK - Hea

lth

cons

ciou

s

Pots

dam

Aarhu

s

Hei

delb

erg

Biltho

ven

UK: Gen

eral

pop

ulat

ion

Cope

nhag

en

Umea

Mal

mo

centres

gra

ms/d

ay

Fatty Acids in Epic Cross Sectional Study (men)

% of Eicosapentaenoic acid (C20:5, n- 3)

0

0,5

1

1,5

2

2,5

3

3,5

4

Denmar

k

Malm

oUmea

Cambr

idge

North

Spa

in

Mur

cia

Pots

dam

Greec

e

Heide

lber

g

Nethe

rland

s

Grana

da

Ragu

sa/N

aples

Mila

n/Va

resa

/ tur

in

Flor

ence

Oxfor

d

Epic center

% o

f Eic

osap

enta

enoi

c ac

id

( C20:5

, n-

3)

Variations of biomarkers of diet between EPIC cohorts

Lycopene, men 45-64 years

0

10

20

30

40

50

60

70

80

90

100

Ragus

a/Nap

les

Vares

e/Tu

rin

Flor

ence

Oxfor

d (*Veg

)

Greec

e

Grana

da

Cambr

idge

Mur

cia

Heide

lber

g

Pots

dam

Denm

ark

The

Nethe

rland

s

Umeå

North

ern

Spain

Malm

ö

mic

rog

/dl

Variations of biomarkers of diet between EPIC cohorts

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

Dietary patterns associated with participating countriesCountry 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

Lifestyle factors and risk of breast cancer in postmenopausal women

24,650 postmenopausal

23,778

Follow up – 31 December 2000- 425 cases of postmenopausal breast cancer

29,875 women

326 prevalent cancers 55 missing information

(alcohol)4,844 premenopausal

872 excluded due to missing information on co-factors

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

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

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

Risikofaktorer for brystkræft (internt justerede)

IRR (95% CI)

En ekstra fødsel 0.87 (0.77-1.00)

Alder ved første fødsel (5 års stigning) 1.02 (0.89-1.16)

Tidligere benign brystsygdom 1.65 (1.30-2.09)

Skolegang 7 år 18-10 år 1.00 (0.80-

1.26) 11 år 1.35 (1.02-1.79)

HRTTidligere 1.10 (0.80-1.51)Nuværende 1.97 (1.50-2.58)

Varighed af HRT (5 års stigning) 1.07 (0.97-1.19)

BMI (5 kg/m2 stigning) 1.07 (0.96-1.20)

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

Epidemiologisk baggrund

En lang række case-kontrol studier

Primære fund: beskyttende effekt

11 kohorte studier

Ingen association til brystkræft

Relativ risiko for brystkræft pr. 100 stigning i indtag af frugt, grøntsager og juice

1,02 (0,98-1,06)Total (f rugt, grøntsager og juice)

1,04 (0,91-1,19)J uice (f rugt og grøntsags)

0,98 (0,89-1,09)Grøntsager

1,05 (0,98-1,11)Frugt

IRR (95% CI )

Olsen, J. Nutr. 2004

Relativ risiko for brystkræft for indtag af grupper af frugt og grøntsager per 100 gram stigning

1,00 (0,99-1,01)Andre f rugter

1,02 (1,00-1,03)Citrusf rugter

1,05 (0,89-1,26)”Stængelgrøntsager”

1,01 (0,94-1,09)Løg, hvidløg

1,01 (0,90-1,14)Svampe

1,01 (0,93-1,09)Kål

0,98 (0,96-1,00)Rodf rugter (ikke kartofler)

1,01 (0,97-1,05)”Frugtgrøntsager”

1,02 (0,91-1,12)Bladgrøntsager

IRR (95% CI )

Olsen, J. Nutr. 2004

Relativ risiko, I RR (95% CI ) for brystkræft for ind-tagelsen af frugt, grøntsager og juice i relation til østrogen receptorstatus

J usteret f or alder, tid i studiet, paritet, benign brysttumor, skoleuddannelse, brug af HRT, alkoholindtagelse, BMI

0,90 (0,81-0,99)1,05 (1,00-1,10)Total

0,67 (0,42-1,08)1,04 (0,89-1,22)J uice

0,92 (0,73-1,16)1,01 (0,90-1,13)Grøntsager

0,92 (0,79-1,08)1,07 (1,00-1,15)Frugt

Østrogen- receptor negativ

Østrogen- receptor positiv

Olsen, J. Nutr. 2004

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?

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

Enterolactone

Enterolactone stammer fra plantelignaner der indgår som en del af fiberkomponenten i planters cellevægge

Lignanerne fermenteres i tyktarmen og optages som enterolactone

Kilder til enterolactone

Fuldkornsprodukter

Grøntsager

Kaffe

Rygning

Fedt

BMI

Johnsen & Hausner 2003

Epidemiologisk baggrund

Relativ risiko for brystkræft pr. 20 nmol/ l stigning i plasma enterolactone

Er- brystkræft

Total brystkræft

0,74 (0,55-1,00)Enterolactone (per 20 nmol/ l)

0,96 (0,88-1,06)Enterolactone (per 20 nmol/ l)

ER+ brystkræft

0,93 (0,86-1,01)Enterolactone (per 20 nmol/ l)

IRR (95% CI )

Olsen, CEBP. 2004

Kvartiler af enterolactone i plasma

0.1- 14.4 nmol/ l

I RR (95% CI )

14.5- 28.1 nmol/ l

I RR (95% CI )

28.2- 47.9 nmol/ l

I RR (95% CI )

48.0- 454.6 nmol/ l

I RR (95% CI )

Total brystkræf t 0.78 (0.52-1.17) 1 0.81 (0.54-1.22) 0.56 (0.37-0.86)

ER+ brystkræf t 0.79 (0.49-1.28) 1 0.96 (0.59-1.55) 0.68 (0.42-1.10)

ER- brystkræf t 0.61 (0.25-1.53) 1 0.43 (0.16-1.15) 0.26 (0.09-0.77)

Enterolactone og brystkræft, kvartiler

Olsen, CEBP 2004

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

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?

Hvorfor ER- brystkræft?

Hypoteser

1) Den beskyttende effekt af enterolactone er primær antioxidativ. Effekten på ER+ bliver ”overskygget” af østrogene risikofaktorer (fra enterolactone eller andet)?

2) ER- brystkræft er et senere stadie af ER+ brystkræft. Enterolactone ”bremser” progressionen fra ER+ til ER- brystkræft?

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

Alkoholoplysninger

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

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 10 (2.3) 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 93 (21.8) 3,794 (16.1)

60 9 (2.1) 357 (1.7)

Median(5-95 percentiles)

Median (5-95 percentiles)

Age (years) 57 (51-64) 57 (51-64)

Age at first birth (years) 23 (18-32) 23 (18-31)

BMI + 24.8 (19.7-33.6)

24.9 (19.9-33.8)

Alcohol (grams per day) * 11.5 (1.3-43.8) 9.7 (0.8-42.1)

Alcohol from different types of beverages

Wine 5.5 (1.3-43.8) 5.4 (0.4-30.7)

Beer 1.1 (0-12.7) 1.0 (0-12.2)

Spirits 0.3 (0-7.8) 0.3 (0-7.8)

* Abstainers and occasional drinkers not included + Weight (kg)/height (m2)

Characteristics of 23,778 women in the Danish Diet, Cancer and Health cohort, 1993-2000

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, 1993-2000

Type of alcohol

Adjusted*Rate ratio (95% CI)

Mutually adjusted**Rate ratio (95% CI)

P for similar effect

Total alcohol 1.10 (1.04-1.16) -

Wine 1.14 (1.06-1.22) 1.13 (1.06-1.22)

Beer 1.01 (0.87-1.17) 0.98 (0.50-1.14) 0.21

Spirits 1.15 (0.92-1.43) 1.09 (0.87-1.36)

* 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

Rate ratio* (RR) in each category of drinking pattern among 23,778 women in the Danish Diet, Cancer and Health cohort, 1993-2000

Drinking occasions nIntake (g/day)

(5-95% percentile) RR (95% CI)

Every day 3,188 (12-70) 1.02 (0.72-1.44)

5-6 times/week 2,471 (10-47) 0.96 (0.68-1.35)

2-4 times/week 7,443 (5-32) 1

Once/week 3,467 (2-15) 0.99 (0.73-1.35)

Less than once/week 6,212 (0.35-8) 0.87 (0.65-1.15)

* 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

Rate ratio of breast cancer by frequency of alcohol consumption

Tjønneland, CCC 2003

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, 1993-2000

Exposure period RR 1 (95% CI) RR 2 (95% CI)

Twenties 0.97 (0.79-1.20) 0.97 (0.78-1.20)

Thirties 0.94 (0.79-1.11) 0.94 (0.79-1.12)

Forties 1.01 (0.88-1.16) 1.01 (0.88-1.16)

Fifties – baseline 1.11 (1.00-1.24) 1.04 (0.91-1.19)

Cumulative intake 3 1.03 (0.99-1.07) 4 0.99 (0.94-1.04)1. 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

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, 1993-2000

Age at drinking start

RR (95% CI)

<16 0.84 (0.55-1.28)

17-18 1.00

19-20 0.99 (0.75-1.32)

21-25 1.06 (0.79-1.42)

26-30 1.38 (0.96-1.99)

>30 1.01 (0.72-1.43)

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

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, 1993-2000

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(0.81-1.49)

- after the 1st birth 135/7,356 1.11(0.84-1.46)

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

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 Uni

t300 301-350 <351-400 400

P forinteracti

on

Alcohol intake 11.0 (0.8-43.8) 10 g 1.21 (1.01-1.45) 1.12 (0.84-

1.48)1.02 (0.83-1.25)

1.03 (0.86-1.22)

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

<=300301-350

351-400>400

<=15

>15 g/d0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

IRR

Total folate intake

<=15

>15 g/d

Alcohol intake

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).

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