Kjøtt og tarmkreft - hva viser epidemiologiske studier?

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Rosamond Merritt
10 years ago
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1 Kjøtt og tarmkreft - hva viser epidemiologiske studier? Christine L. Parr (Folkehelseinstituttet/Univ. i Oslo) Møte Forskning med fokus på tarmkreft og kjøtt

2 Min bakgrunn Hovedfag i ernæring PhD/postdok i epidemiologi, Avd. for biostatisikk ved UiO: Kreft og kosthold/livsstilsfaktorer i store befolkningsstudier (kohorter) Metoder i kostholdsforskning, vekt på spørreskjema (FFQ) Datakvalitet, valideringsstudier, målefeil, anvendt statistisk korreksjon Prosjekt «Kostråd og kreftforebygging»

3 Epidemiological study 2013

4 Expert evaluations/meta-analyses: meat and colorectal cancer (CRC)

5 Meta-analyses Word Cancer Research Fund/American Inst. for Cancer Research (WCRF/AICR): 1997, 2007 Continuous Update Project (CUP) 2011: Chan DS et al. PloS ONE papers/24 studies (high-low) & 26/21 dose-resp. Stratifications: red & processed meat, subsites, sex, region (Eur/North America/Asia-Pacific) Huxley RR et al. Int. J Cancer 2009 Alexander DD et al.. Eur J Cancer Prev & 2011

7 Evidence red & processed meat: WCRF/AICR: From convincing (2007) to supportive (2011) Red meat: CRC risk per 100 g/day increase reduced from 29% to 17% Processed meat: CRC risk per 50 g/day increase was similar, 21% and 18% Sex difference: not established Regional differences: red meat & colon cancer Stronger association in Eur than N. Am & Asia Few studies on colon subsites (proximal/distal)

8 Chan DS et al. PloS ONE 2011

10 What is processed meat? No generally agreed definition. Used inconsistently in epidemiological studies...meats preserved by smoking, curing or salting, or by addition of preservatives. Ex: ham, bacon, salami, hot dogs/ sausages. Minced meats/hamburgers sometimes fall inside this definition, often if preserved chemically, but not always.

11 Colorectal cancer: multifactorial

14 Norwegian Women and Cancer Cohort Study (NOWAC) Kvinner og Kreft studien

15 Data material/methods 84,538 NOWAC women: nationwide cohort Age yrs at inclusion: or Linkage to Cancer Registry (through 2009) Median follow-up 11.1 yrs Validated food frequency questionnaire (FFQ)

16 Statistics Multivariable Cox regression Main models adjusted for intake of energy, alcohol, fiber, calcium, BMI, smoking status (never, ex, current), and physical activity score Measurement error correction by regression calibration (Spiegelman D et al. Am J Clin Nutr 1997) Reference: 4 24-HDRs during one year ( ) by telephone, n = 238 (Hjartåker et al. 2007)

17 Cases by subsites of the colon-rectum Colon cases: 459 Proximal: 242 Distal: 167 Rectum cases: 215

18 Meat questions in FFQ: what s red and processed? R R R P? P D D C D P R = Red P = Processed C = Chicken D = Dishes with meat

19 CRC risk: red & processed meat Red (n=83,997) Processed (n=84,210) g/day Cases HRs (95% CI) < < (0.80, 1.26) 15-< (0.83, 1.36) 25-< (0.58, 1.14) (0.61, 1.39) p trend 0.45 g/day Cases HRs (95% CI) < < (0.83, 1.28) 30-< (0.80, 1.29) 45-< (0.78, 1.38) (1.19, 2.12) p trend 0.02

20 Reviewer comment no. 1: Shouldn t meatballs/hamburgers be included in the fresh red meat group as these foods usually are not preserved with nitrate/nitrite, smoking, or curing? What are the results for red meat and processed meat if meatballs and hamburgers are included in red meat?

21 Results processed meat With meatballs (n=84,210) g/day Cases HRs (95% CI) < < (0.83, 1.28) 30-< (0.80, 1.29) 45-< (0.78, 1.38) (1.19, 2.12) p trend 0.02 Without meatballs (n=83,460) g/day Cases HRs (95% CI) < < (0.81, 1.17) 30-< (0.80, 1.27) 45-< (0.94, 1.64) (0.85, 1.85) p trend 0.12 Per 50 g/day increase HR = 1.21 (95% ) HR = 1.25 (95% CI: )

24 Nitrates/nitrites in Norwegian meat products?

25 Nitrate/nitrites allowed? SNT/Norwegian food authoroties say: Kjøttdeig er ikke et kjøttprodukt, men faller inn under matvarekategori 8.1 ubearbeidet kjøtt og det har ikke vært/er ikke tillatt med nitritt/nitrat Ferdigkjøpte/varmebeh. kjøttkaker/ karbonader: ikke varmebehandlede ja, i varmebehandlede kun nitritt og det skilles på mengde utfra om produktet er sterilisert eller ei.

26 Analyzed values: SNT Rogaland 2001 Our reply: The level (mg/kg) in meatballs/hamburgers was generally lower (max 23 for nitrate and 7 for nitrite, 5 products) than for heated sausages (max 35 for nitrate and 20 for nitrite, 13 products), but similar to that found in many other items usually defined as processed meat (several cured hams and salami-style sausages).

27 Hypothesized mechanism(s) Related to Additives/preservatives: Nitrites (mainly E250) High temp cooking heterocyclic amines (HCAs), carcinogenic in animal models Heme iron N-nitroso compounds (NOCs) (Bovine viruses)

28 No effect of cooking method

29 Other studies on HCAs Detailed meat cooking questionnaires developed to estimate HCA intake Mutagen database CHARRED developed in the US ( Inconsistent findings NIH-AARP cohort Multiethnic Cohort Study Genetic variations in enzymes responsible for bioactivation/detoxification may be important

30 Why no effect of red meat? Chan DS et al. PloS ONE 2011

31 Why no effect of red meat? Larsson SC et al. Int J Cancer 2005

32 Chan DS et al. PloS ONE 2011

33 Main results NOWAC No increase in risk for red meat intake ( 30 g/day) No effect of meat cooking methods Intake 60 g/day associated with sig. increased risk of CRC in all subsites, including distal (HR=1.69) and proximal colon (HR=2.13) Effect mainly driven by intake of sausages. Norwegian women have high intake of processed meat (European context)

34 European Prospective Investigation into Cancer and Nutrition (EPIC) 500, 000 participants 23 study centers 10 countries, including Norway

35 A sample of single 24-HDRs from the entire cohort, including about 1,800 NOWAC women (data collected during ), showed that the Norwegian/NOWAC women had the highest mean intake of total processed meat (about 45 g/day), the main source being heated sausages (intake about 20 g/day), while the mean intake of fresh red meat (about 30 g/day) was at the low end of the population range for women in all EPIC countries.

37 The puzzle Could processed meat be an indicator of poor diet/lifestyle and low socioeconomic status Negative association with household income in Norway If CRC risk is affected by Cooking/HCA level: why no assoc. with chicken? Heme iron: why not higher risk for red meat? Nitrites: why effect of red meat? Different mechanisms for red & processed meat? Presence of anti-carcinogens in the diet?

38 Thanks!

39 Current dietary recommendation To prevent chronic diseases, incl cancer: Limit intake of red and processed meat Adults: max 500 g red meat/wk, little should be processed

Q&A on the carcinogenicity of the consumption of red meat and processed meat

Q&A on the carcinogenicity of the consumption of red meat and processed meat Q. What do you consider as red meat? A. Red meat refers to all mammalian muscle meat, including, beef, veal, pork, lamb, mutton, horse, and goat. Q. What do you consider as processed meat? A. Processed