Cancer outcomes associated with food food contaminants obesity

Cancer outcomes associated with food, food contaminants, obesity and dietary patterns: from science to policy Operationalising the WCRF/AICR cancer prevention recommendations using an index score: recent meta-analysis in relation to cancer incidence and mortality Dora Romaguera, Doris Chan, Giota Mitrou, Teresa Norat 101 M-T 1 Track 1 - Stemming the tide: innovations in prevention and screening Disclosure of interest: None

OUTLINE • WCRF/AICR Cancer prevention recommendations - WCRF/AICR sub-recommendations • The WCRF/AICR score - The WCRF/AICR score: an example (EPIC study) • The WCRF/AICR score and health outcomes: systematic review and meta-analysis - The WCRF/AICR score and breast cancer incidence: dose-response meta- analysis - The WCRF/AICR score and total cancer incidence: umbrella meta-analysis - The WCRF/AICR score and cancer mortality: systematic review • Conclusions and future research

WCRF/AICR Cancer prevention recommendations Wold Cancer Research Fund / American Institute for Cancer Research (WCRF / AICR) Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective Washington DC: AICR, 2007 The Panel emphasizes the importance of not

WCRF/AICR sub-recommendations Recommendation Sub-recommendations (personal recommendations) 1) Be as lean as possible without becoming underweight 1. 1) Ensure that body weight through childhood and adolescent growth projects 3 towards the lower end of the normal BMI range at age 21 1. 2) Maintain body weight within the normal range from age 21 1. 3) Avoid weight gain and increases in waist circumference throughout adulthood 2) Be physically active for at least 30 minutes every day 2. 1) Be moderately physically active, equivalent to brisk walking, for at least 30 minutes every day 2. 2) As fitness improves, aim for 60 minutes or more of moderate, or for 30 minutes or more of vigorous, physical activity every day 2. 3) Limit sedentary habits such as watching television 3) Limit consumption of energy-dense foods 3. 1) Consume energy-dense foods sparingly 3. 2) Avoid sugary drinks 3. 3) Consume 'fast foods’ sparingly, if at all 4) Eat more of a variety of vegetables, fruits, wholegrains, & pulses such as beans 4. 1) Eat at least five portions/servings (at least 400 g or 14 oz) of a variety of non-starchy vegetables and of fruits every day 4. 2) Eat relatively unprocessed cereals (grains) and/or pulses (legumes) with every meal 4. 3) Limit refined starchy foods 4. 4) People who consume starchy roots or tubers as staples also to ensure intake of sufficient non-starchy vegetables, fruits, and pulses (legumes) 5) Limit consumption of red meats (such as beef, pork and lamb) and avoid processed meats 5. 1) People who eat red meat to consume less than 500 g (18 oz) a week, very little if any to be processed 6) If alcoholic drinks are consumed, limit consumption to no more than two drinks a day for men and one drink a day for women 6. 1) If alcoholic drinks are consumed, limit consumption to no more than two drinks a day for men and one drink a day for women

WCRF/AICR sub-recommendations Recommendation Sub-recommendations (personal recommendations) 7) Limit consumption of salt & avoid mouldy grains and cereals 7. 1) Avoid salt-preserved, salted, or salty foods; preserve foods without using salt 7. 2) Limit consumption of processed foods with added salt to ensure an intake of less than 6 g (2. 4 g sodium) a day 7. 3) Do not eat mouldy cereals (grains) or pulses (legumes). 8) Aim to meet nutritional needs through diet alone 8. 1) Dietary supplements are not recommended for cancer prevention 9) It is best for mothers to breastfeed exclusively for up to 6 months and then add other liquids & foods 9. 1) Breastfeeding protects both mother and child 9. 2) 'Exclusively' means human milk only, with no other food or drink, including water 9. 3) In accordance with the UN Global Strategy on Infant and Young Child Feeding 10) After treatment, cancer survivors should follow the recommendations for cancer prevention 10. 1) Cancer survivors are people who are living with a diagnosis of cancer, including those who have recovered from the disease 10. 2) This recommendation does not apply to those who are undergoing active treatment, subject to the qualifications in the text 10. 3) This includes all cancer survivors, before, during, and after active treatment

The WCRF/AICR score § In last four years there has been increased interest in investigating adherence to the WCRF/AICR recommendations in relation to health outcomes § A scoring system has been developed to assess the degree of adherence to the WCRF/AICR recommendations and applied in different epidemiological studies

The WCRF/AICR score: an example European Prospective Investigation in Cancer and Nutrition (EPIC) (Romaguera et al, AJCN 2012) 1 0. 5 0 BODY MASS INDEX (BMI) 1 -Be as lean as possible without becoming underweight 18. 5 ≤ BMI < 25 25 ≤ BMI < 30 BMI ≥ 30 or BMI < 18. 5 PHYSICAL ACTIVITY (PA) 2 -Be physically active for at least 30 minutes every day Manual work or Vigorous PA > 2 h/w or Cycling + Sports > 30 m/d Cycling + Sports 15 - 30 m/d Cycling + Sports <15 m/d

The WCRF/AICR score: an example European Prospective Investigation in Cancer and Nutrition (EPIC) (Romaguera et al, AJCN 2012) Average 1 0. 5 0 FOODS THAT PROMOTE WEIGHT GAIN (FWG) 3. 1 -Limit consumption of energy-dense foods 3. 2 -Avoid sugary drinks ED ≤ 125 kcal/100 g 125 < ED < 275 kcal/100 g ED ≥ 125 kcal/100 g 0 g/d ≤ 250 g/d > 250 g/d PLANT FOODS (PF) 4. 1 –Eat at least 5 servings fruit and vegetables a day 4. 2 –Eat unprocessed cereals and pulses Average ≥ 400 g/d 200 - <400 g/d <200 g/d Dietary fibre ≥ 25 g/d Dietary fibre 12. 5 - <25 g/d Dietary fibre <12. 5 g/d

The WCRF/AICR score: an example European Prospective Investigation in Cancer and Nutrition (EPIC) (Romaguera et al, AJCN 2012) 1 0. 5 0 MEAT CONSUMPTION (MEAT) 5 -Limit consumption of red meats and avoid processed meats Red + Processed meats <500 g/d and Processed meat <3 g/d Red + Processed meats <500 g/d and Processed meat 3 - <50 g/d Red + Processed meats ≥ 500 g/d and/or Processed meat ≥ 50 g/d ALCOHOL INTAKE (ALC) 6 -Limit alcoholic drinks to 2 for men and 1 for women a day Ethanol ≤ 20 g/d men ≤ 10 g/d women Ethanol >20 -30 g/d men >10 -20 g/d women Ethanol >30 g/d men >20 g/d women

The WCRF/AICR score: an example European Prospective Investigation in Cancer and Nutrition (EPIC) (Romaguera et al, AJCN 2012) 1 7 -Limit consumption of salty foods 0. 5 0 Insufficient data avaible 8 -Don´t use supplements to protect against cancer Not applicable BREAST FEEDING (BF) 9 -Breastfeed exclusively for up to 6 months 10 -Cancer survivors should follow the recommendations Cumulative BF ≥ 6 months Cumulative BF >0 - <6 months Not applicable Cumulative BF 0 months Score Range: Range 0 – 6 points in Men 0 – 7 points in Women

The WCRF/AICR score and health outcomes Systematic review and meta-analyses 191 publications indentified in PUBMED until April 2016 154 publications excluded on the bases of title and abstract 37 full-text publications retrieved and assessed for inclusion 15 publications excluded for not fulfilling the inclusion criteria: 1 review 8 based on 1997 WCRF/AICR guidelines 6 descriptive publications without health outcome assessment 22 publications included in this systematic review: 8 cross-sectional studies 4 case-control studies 10 cohort studies 7 publications included in the breast-cancer meta-analysis 1 case-control studies 6 cohort studies 9 publications included in the total cancer umbrella meta-analysis 3 case-control studies 6 cohort studies

The WCRF/AICR score and breast cancer incidence Author, Year, Country Study name, Study design, Sex, age (years) Cases/total N (years FU) Cases/controls Outcome Components of the WCRF/AICR score RR (95%CI) per 1 -unit increase 0. 89 (0. 83; 0. 95) Harris, 2016 Sweden Swedish Mammography Cohort (SMC) Cohort, W (61. 4 y) 1388/31514 (15 y) Breast cancer 7 recommendations (BW, PA, FPWG, PF, A, SU) Nomura, 2016, USA Iowa Women’s Health Study (IWHS) Cohort, W (61. 7 y) 3189/36626 (1986 – 2010) Postmenopausal breast cancer 7 recommendations (BW, PA, FPWG, PF, A, S) 0. 76 (0. 67; 0. 87) Makarem, 2015 USA Framingham Offspring cohort Cohort M, W (66 y) 124/2983 (11. 5 y) Breast cancer 7 recommendations (BW, PA, FPWG, PF, A, FPPP) 0. 87 (0. 74; 1. 03) Catsburg, 2014 Canada Canadian National Breast Screening Study Cohort W (40 -59 y) 1970/47130 (16. 6 y) Breast cancer 7 recommendations (BW, PA, FPWG, PF, A, S) 0. 95 (0. 91; 0. 98) Hastert, 2013 USA Vitamins and lifestyle (VITAL) Study Cohort, M, W (50 -76 y) 899/30797 (6. 7 y) Postmenopausal breast cancer 6 recommendations (BW, PA, FPWG, PF, A) 0. 89 (0. 84; 0. 95) Romaguera, 2012 Europe 10 countries EPIC, Cohort W (25 -70 y) 9358/386355 (11 y) Breast cancer 6 + 1 (in women) (BW, PA, FPWG, PF, A, BF) 0. 95 (0. 93; 0. 97) Castelló, 2015, Spain Epi. GEICAM, Case-control W (22 -71 y) Breast cancer 8 + 1 recommendations (BW, PA, FPWG, PF, A, S, SU, BF) 1. 22 (1. 11; 1. 34) “Per 1 -unit decrease” Systematic review 973/973

The WCRF/AICR score and breast cancer incidence Dose-response meta-analyses

The WCRF/AICR score and total cancer incidence Author, Year, Country Study name, Study design, Sex, age (years) Systematic review Cases/total N (years Follow-up) Cases/controls Outcome Components of the WCRF/AICR score RR (95%CI) per 1 -unit increment Total cancer (a) Breast (b) Endometrial (c) Ovarian (d) Prostate (e) Colorectal (f) Lung (g) Bladder (h) Pancreas (i) Kidney (j) Stomach (k) UADT (l) Liver (m) Esophageal 6 + 1 (in women) 6 (in men) (BW, PA, FPWG, PF, A, BF) 0. 95 (0. 93; 0. 97) (a) 0. 95 (0. 93; 0. 97) (b) 0. 88 (0. 83; 0. 94) (c) 0. 95 (0. 89; 1. 02) (d) 1. 00 (0. 96; 1. 04) (e) 0. 88 (0. 84; 0. 91) (f) 0. 92 (0. 89; 0. 96) (g) 0. 94 (0. 89; 1. 00) (h) 1. 00 (0. 92; 1. 08) (i) 0. 91 (0. 85; 0. 99) (j) 0. 84 (0. 78; 0. 91) (k) 0. 82 (0. 74; 0. 90) (l) 0. 90 (0. 81; 0. 99) (m) 0. 84 (0. 73; 0. 96) 6 recommendations (BW, PA, FPWG, PF, A) 0. 99 (0. 94; 1. 05) Romaguera, 2012 Europe 10 countries EPIC, Cohort M/W (25 -70 y) 36994/386355 (11 y) (a) 9358 (b) 1148 (c) 906 (d) 4039 (e) 3880 (f) 2462 (g) 1514 (h) 783 (i) 745 (j) 696 (k) 602 (l) 522 (m) 312 Er, 2014 UK PSA-tested cohort Protec. T trial Case-control M (50 -69 y) 1806/12005 PSA-detected prostate cancer Makarem, 2015 USA Framingham Offspring cohort Cohort M, F (66 y) 480/2983 (11. 5 y) (a) 124 (b) 153 (c) 63 Obesity-related cancers (a) Breast (b) Prostate (c) Colorectal 7 recommendations (BW, PA, FPWG, PF, A, FPPP) 0. 94 (0. 86; 1. 02) (a) 0. 87 (0. 74; 1. 03) (b) 1. 08 (0. 92; 1. 27) (c) 0. 87 (0. 68; 1. 12) Lucas, 2016, Italy Case-control M, F (63 y) 326/652 Pancreatic cancer 7 recommendations (BW, PA, FPWG, PF, A, S) 0. 72 (0. 60; 0. 87)

The WCRF/AICR score and total cancer incidence Umbrella meta-analyses

The WCRF/AICR score and total cancer incidence Umbrella meta-analyses

The WCRF/AICR score and cancer mortality Systematic review Author, Year, Country Study name, Study design, Sex, age (years) Vergnaud, 2013 Europe 10 countries EPIC, Cohort M/W (25 -70 y) 23828/378864 (12. 8 y) Inoue-Choi, 2013 USA Iowa Women’s Health Study Cohort F (78. 9 y) 461/2017 (5. 4 y) (a) 184 Hastert, 2014 USA Vitamins and lifestyle (VITAL) Study Cohort, M, F (50 -76 y) Romaguera, 2015, Europe 10 countries EPIC, Cohort M/W (25 -70 y) Cases/total N (years Follow-up) 1595/57841 (7. 7 y) 872/3292 (4. 2 y) Outcome Secondary outcomes Total death Death due to: (a) Cancer Components of the WCRF/AICR score Score range Comparison High (5 -6 M/6 -7 W) 6 + 1 (in women) versus Low (0 -2 M/0 -3 W) 6 (in men) (BW, PA, FPWG, PF, AF, 1 -unit increase A, BF) All-cause mortality among older female 7 recommendations (BW, Q 4 (6. 0 -8. 0) versus Q 1 cancer survivors PA, FPWG, PF, A, S) (1. 5 -4. 0) (a) Cancer-specific mortality 6 recommendations (BW, PA, FPWG, PF, A) RR (95%CI) for secondary outcomes 0. 66 (0. 60; 0. 73) (a) 0. 80 (0. 69; 0. 93) 0. 87 (0. 86; 0. 88) (a) 0. 91 (0. 89; 0. 93) 0. 67 (0. 49; 0. 90) (a) 0. 63 (0. 39; 1. 04) Meeting 5+ versus 0 recommendations 0. 39 (0. 24; 0. 62) Per recommendation 0. 90 (0. 85; 0. 94) High (4 -6 M/5 -7 W) CRC-specific mortality 6 + 1 (in women) versus Low (0 -2 M/0 -3 W) among CRC cases; 6 (in men) (a) Overall mortality (BW, PA, FPWG, PF, AF, 1 -unit increase among CRC cases A, BF) 0. 70 (0. 56; 0. 89) (a) 0. 79 (0. 65; 0. 98) 0. 90 (0. 83; 0. 97) (a) 0. 93 (0. 87; 0. 99)

Conclusions and future research q Substancial evidence indicates that adherence to the WCRF/AICR recommendation for cancer prevention, is associated with lower risk of cancer incidence – mostly breast cancer – and cancer mortality; q Despite different definitions used to evaluate adherence to the WCRF/AICR recommendations, results among different studies are mostly consistent; q Since our last literature review, several new papers have been published on the WCRF/AICR and different health outcomes – in diverse populations –, therefore the meta-analyses need to be updated.

Thank you very much for your attention, Dora Romaguera MSC PHD (1, 2) (1) Instituto de Investigación Sanitaria de Palma (Id. ISPa); CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN). Spain mariaadoracion. romaguera@ssib. es (2) Imperial College London, UK d. romaguera-bosch@imperial. ac. uk