Cancer outcomes associated with food, food contaminants, obesity and dietary patterns: from science to policy

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1 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 101M-T1 Track 1 - Stemming the tide: innovations in prevention and screening Disclosure of interest: None

2 OUTLINE WCRF/AICR Cancer prevention recommendations - WCRF/AICR sub-recommendations The WCRF/AICR score - The WCRF/AICR score: an example ( study) The WCRF/AICR score and health outcomes: systematic review and metaanalysis - 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

3 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 smoking

4 WCRF/AICR sub-recommendations Recommendation Sub-recommendations (personal recommendations) 1) Be as lean as possible without becoming underweight 2) Be physically active for at least 30 minutes every day 3) Limit consumption of energy-dense foods 4) Eat more of a variety of vegetables, fruits, wholegrains, & pulses such as beans 5) Limit consumption of red meats (such as beef, pork and lamb) and avoid processed meats 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 11) Ensure that body weight through childhood and adolescent growth projects3 towards the lower end of the normal BMI range at age 21 12) Maintain body weight within the normal range from age 21 13) Avoid weight gain and increases in waist circumference throughout adulthood 21) Be moderately physically active, equivalent to brisk walking, for at least 30 minutes every day 22) As fitness improves, aim for 60 minutes or more of moderate, or for 30 minutes or more of vigorous, physical activity every day 23) Limit sedentary habits such as watching television 31) Consume energy-dense foods sparingly 32) Avoid sugary drinks 33) Consume 'fast foods sparingly, if at all 41) 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 42) Eat relatively unprocessed cereals (grains) and/or pulses (legumes) with every meal 43) Limit refined starchy foods 44) People who consume starchy roots or tubers as staples also to ensure intake of sufficient non-starchy vegetables, fruits, and pulses (legumes) 51) People who eat red meat to consume less than 500 g (18 oz) a week, very little if any to be processed 61) If alcoholic drinks are consumed, limit consumption to no more than two drinks a day for men and one drink a day for women

5 WCRF/AICR sub-recommendations Recommendation Sub-recommendations (personal recommendations) 7) Limit consumption of salt & avoid mouldy grains and cereals 71) Avoid salt-preserved, salted, or salty foods; preserve foods without using salt 72) Limit consumption of processed foods with added salt to ensure an intake of less than 6g (24g sodium) a day 73) Do not eat mouldy cereals (grains) or pulses (legumes) 8) Aim to meet nutritional needs through diet alone 81) 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 91) Breastfeeding protects both mother and child 92) 'Exclusively' means human milk only, with no other food or drink, including water 93) 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 101) Cancer survivors are people who are living with a diagnosis of cancer, including those who have recovered from the disease 102) This recommendation does not apply to those who are undergoing active treatment, subject to the qualifications in the text 103) This includes all cancer survivors, before, during, and after active treatment

6 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

7 The WCRF/AICR score: an example European Prospective Investigation in Cancer and Nutrition () (Romaguera et al, AJCN 2012) 1-Be as lean as possible without becoming underweight 2 -Be physically active for at least 30 minutes every day BODY MASS INDEX (BMI) 185 BMI < BMI < 30 PHYSICAL ACTIVITY (PA) Manual work or Vigorous PA > 2 h/w or Cycling + Sports > 30 m/d Cycling + Sports m/d BMI 30 or BMI < 185 Cycling + Sports <15 m/d

8 The WCRF/AICR score: an example European Prospective Investigation in Cancer and Nutrition () (Romaguera et al, AJCN 2012) Average 31 -Limit consumption of energy-dense foods 32 -Avoid sugary drinks 41 Eat at least 5 servings fruit and vegetables a day 42 Eat unprocessed cereals and pulses Average FOODS THAT PROMOTE WEIGHT GAIN (FWG) 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) 400 g/d <400 g/d <200 g/d Dietary fibre 25 g/d Dietary fibre <25 g/d Dietary fibre <125 g/d

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

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

11 The WCRF/AICR score and health outcomes Systematic review and meta-analyses 191 publications indentified in PUBMED until April publications excluded on the bases of title and abstract 37 full-text publications retrieved and assessed for inclusion 22 publications included in this systematic review: 8 cross-sectional studies 4 case-control studies 10 cohort studies 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 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

12 Author, Year, Country Study name, Study design, The WCRF/AICR score and breast Outcome cancer incidence Sex, age (years) Cases/controls Harris, 2016 (SMC) Systematic review Sweden Nomura, 2016, USA Swedish Mammography Cohort Cohort, W (614 y) Iowa Women s Health Study (IWHS) Cohort, W (617 y) Cases/total N (years FU) 1388/31514 (15 y) 3189/36626 ( ) Breast cancer Postmenopausal breast cancer Components of the WCRF/AICR score 7 recommendations (BW, PA, FPWG, PF, AF, A, SU) 7 recommendations (BW, PA, FPWG, PF, AF, A, S) RR (95%CI) per 1-unit increase 089 (083;095) 076 (067; 087) Makarem, 2015 USA Framingham Offspring cohort Cohort M, W (66 y) 124/2983 (115 y) Breast cancer 7 recommendations (BW, PA, FPWG, PF, AF, A, FPPP) 087 (074;103) Catsburg, 2014 Canada Canadian National Breast Screening Study Cohort W (40-59 y) 1970/47130 (166 y) Breast cancer 7 recommendations (BW, PA, FPWG, PF, AF, A, S) 095 (091;098) Hastert, 2013 USA Vitamins and lifestyle (VITAL) Study Cohort, M, W (50-76 y) 899/30797 (67 y) Postmenopausal breast cancer 6 recommendations (BW, PA, FPWG, PF, AF, A) 089 (084;095) Romaguera, 2012 Europe 10 countries, Cohort W (25-70 y) 9358/ (11 y) Breast cancer (in women) (BW, PA, FPWG, PF, AF, A, BF) 095 (093;097) Castelló, 2015, Spain EpiGEICAM, Case-control W (22-71 y) 973/973 Breast cancer recommendations (BW, PA, FPWG, PF, AF, A, S, SU, BF) 122 (111;134) Per 1-unit decrease

13 The WCRF/AICR score and breast cancer incidence Dose-response meta-analyses per 1 point % Author Year RR (95% CI) Weight Study Prospective Cohort Harris (083, 095) 1390 SMC Nomura (081, 094) 1255 IWHS Makarem (074, 103) 417 FHS-Offspring Cohort Catsburg (091, 098) 2062 CNBSS Hastert (084, 095) 1509 VITAL Romaguera (093, 097) 2402 Subtotal (I-squared = 511%, p = 0069) Case-Control 092 (089, 095) 9035 Castelló (075, 090) 965 EpiGEICAM Subtotal (I-squared = %, p = ) Overall (I-squared = 664%, p = 0007) 082 (075, 090) 091 (087, 094) NOTE: Weights are from random effects analysis

14 Author, Year, Study name, Study design, The WCRF/AICR score and Outcome total cancer incidence Country WCRF/AICR score Sex, age (years) Cases/controls Systematic review Romaguera, 2012 Europe 10 countries Er, 2014 UK Makarem, 2015 USA, Cohort M/W (25-70 y) PSA-tested cohort ProtecT trial Case-control M (50-69 y) Framingham Offspring cohort Cohort M,F (66 y) Cases/total N (years Follow-up) 36994/ (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) / /2983 (115 y) (a) 124 (b) 153 (c) 63 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 PSA-detected prostate cancer Obesity-related cancers (a) Breast (b) Prostate (c) Colorectal Components of the (in women) 6 (in men) (BW, PA, FPWG, PF, AF, A, BF) 6 recommendations (BW, PA, FPWG, PF, AF, A) 7 recommendations (BW, PA, FPWG, PF, AF, A, FPPP) RR (95%CI) per 1-unit increment 095 (093;097) (a) 095 (093;097) (b) 088 (083;094) (c) 095 (089;102) (d) 100 (096;104) (e) 088 (084;091) (f) 092 (089;096) (g) 094 (089;100) (h) 100 (092;108) (i) 091 (085;099) (j) 084 (078;091) (k) 082 (074;090) (l) 090 (081;099) (m) 084 (073;096) 099 (094;105) 094 (086;102) (a) 087 (074;103) (b) 108 (092;127) (c) 087 (068;112) Lucas, 2016, Italy Case-control M, F (63 y) 326/652 Pancreatic cancer 7 recommendations (BW, PA, FPWG, PF, AF, A, S) 072 (060;087)

15 The WCRF/AICR score and total cancer incidence Umbrella meta-analyses Author Year per 1 point RR (95% CI) Study Bladder cancer Breast cancer Harris 2016 Nomura 2016 Castelló 2015 Makarem 2015 Catsburg 2014 Hastert 2013 Colorectal cancer Makarem 2015 Endometrial Cancer Kidney cancer Liver cancer Lung cancer Oesophageal cancer Ovarian cancer Pancreatic cancer Lucas 2016 Prostate cancer Makarem 2015 Er 2014 Stomach cancer Upper Aerodigestive Cancer 094 (089, 100) 089 (083, 095) 088 (081, 094) 082 (075, 090) 087 (074, 103) 095 (091, 098) 089 (084, 095) 095 (093, 097) 087 (068, 112) 088 (084, 091) 088 (083, 094) 091 (085, 099) 090 (081, 099) 092 (089, 096) 084 (073, 096) 095 (089, 102) 072 (060, 087) 100 (092, 108) 108 (092, 127) 099 (094, 105) 100 (096, 104) 084 (078, 091) 082 (074, 090) SMC IWHS EpiGEICAM FHS-Offspring Cohort CNBSS VITAL FHS-Offspring Cohort Italian case-control study FHS-Offspring Cohort ProtecT

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

17 The WCRF/AICR score and cancer mortality Systematic review Author, Year, Country Study name, Study design, Sex, age (years) Cases/total N (years Follow-up) Outcome Secondary outcomes Components of the WCRF/AICR score Score range Comparison RR (95%CI) RR (95%CI) for secondary outcomes Vergnaud, 2013 Europe 10 countries, Cohort M/W (25-70 y) 23828/ (128 y) Total death Death due to: (a) Cancer (in women) 6 (in men) (BW, PA, FPWG, PF, AF, A, BF) High (5-6 M/6-7 W) versus Low (0-2 M/0-3 W) 1-unit increase 066 (060;073) (a) 080 (069;093) 087 (086;088) (a) 091 (089;093) Inoue-Choi, 2013 USA Iowa Women s Health Study Cohort F (789 y) 461/2017 (54 y) (a) 184 All-cause mortality among older female cancer survivors (a) Cancer-specific mortality 7 recommendations (BW, PA, FPWG, PF, AF, A, S) Q4 (60-80) versus Q1 (15-40) 067 (049;090) (a) 063 (039;104) Hastert, 2014 USA Vitamins and lifestyle (VITAL) Study Cohort, M, F (50-76 y) 1595/57841 (77 y) Cancer-specific mortality 6 recommendations (BW, PA, FPWG, PF, AF, A) Meeting 5+ versus 0 recommendations 039 (024;062) Per recommendation 090 (085;094) Romaguera, 2015, Europe 10 countries, Cohort M/W (25-70 y) 872/3292 (42 y) CRC-specific mortality among CRC cases; (a) Overall mortality among CRC cases (in women) 6 (in men) (BW, PA, FPWG, PF, AF, A, BF) High (4-6 M/5-7 W) versus Low (0-2 M/0-3 W) 1-unit increase 070 (056;089) (a) 079 (065;098) 090 (083;097) (a) 093 (087;099)

18 Conclusions and future research 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; Despite different definitions used to evaluate adherence to the WCRF/AICR recommendations, results among different studies are mostly consistent; 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

19 Thank you very much for your attention, Dora Romaguera MSC PHD (1,2) (1) Instituto de Investigación Sanitaria de Palma (IdISPa); CIBER Fisiopatología de la Obesidad y Nutrición (CIBER- OBN) Spain mariaadoracionromaguera@ssibes (2) Imperial College London, UK dromaguera-bosch@imperialacuk