Nutritional risk factors of Colorectal Cancer in Morocco

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1 Kingdom of Morocco Workshop Kuala Lumpur, October 2 nd, 2018 Session title: Understanding global nutrition habits and dynamics as a step towards cancer prevention and control (T1-18) Nutritional risk factors of Colorectal Cancer in Morocco K EL RHAZI, MD, PhD

Epidemiologic transition Life expectancy trend, Morocco 1967-2014 Introduction

endocriniènnes, nutritionnelles et métaboliques Maladies dont l'origine se situe

75-79 ans 70-74 ans 65-69 ans 60-64 ans 55-59 ans 50-54 ans 45-49 ans 40-44 ans

2000000 1000000 0 1000000 2000000 Leading causes of death, 2013.

4 0 5 10 15 20 25 Moyenne de consommation per capita (Kg/personne/an) des

2000/2003. (FAO, Division des statistiques) 1. S Benjelloun.

Commissariat au Plan 3. Direction de la statistique.

2 Epidemiologic transition Life expectancy trend, Morocco Introduction Nutritional transition RGPH 2014 Evolution of burden disease Maladies endocriniènnes, nutritionnelles et métaboliques Maladies dont l'origine se situe au cours de la prériode péinatale Tumeurs Maladies de l'appareil circulatoire H ans ans ans ans ans ans ans ans ans ans ans ans ans ans 5-9 ans 0-4 ans Fem Leading causes of death, Source: Health Sales in 2014 Morocco Ministry of Health % Moyenne de consommation per capita (Kg/personne/an) des différents groupes alimentaires au cours des périodes 1968/1970, 1990/1992, 2000/2003. (FAO, Division des statistiques) 1. S Benjelloun. Nutrition transition in Morocco. Public Health Nutrition 2002: 5(1A), Direction de la Statistique. Consommation et Dépenses des Ménages 1984/85, 2000/2001 Rabat, Maroc: Haut Commissariat au Plan 3. Direction de la statistique. Enquête nationale sur le niveau de vie des ménages 1990/1991, 1998/1999, Rabat, Maroc.: Haut Commissariat au Plan. Source : Extrait de Zeghichi-Hamria, World Rev Nutr Diet Source : Extrait de Zeghichi-Hamria, World Rev Nutr Diet

3 Colorectal Cancer in Morocco, Casablanca Cancer registry: First population registry in Morocco taking place in Casablanca region (11% general population) Incidence du cancer du colon, RCRC, 2004 Incidence du cancer du rectum, RCRC, 2004

4 What are the contributing nutritional factors to the incidence of cancer in Morocco? Some results from a Moroccan National case control study

5 Methodology - short Reminder Objective: We investigated associations between nutritional factors and colorectal cancer (CRC) risk in Morocco. Colon and rectal cancer 1516 Cases 1516 Controls Matched by Age (5 years) + sex+ center Moroccan Food Frequency Questionnaire* * Centers of the National Case control study *K EL Kinany et al. Nutr J ;17(1):61. Adaptation and validation of a food frequency questionnaire (FFQ) to assess dietary intake in Moroccan adults.

6 Table 1. Some general characteristics of the study population (N=2906). Data Cases (n=1453) Controls (n=1453) p N (%) N (%) Center Rabat 479 (33.00) Casablanca 475 (32.70) Oujda 249 (17.13) NS Fez 224 (15.40) Marrakech 26 (01.77) Sex Female 737 (50.70) NS Male 716 (49.30) Marital status Single 136 (9.40) 141 (9.7) Married 1109 (76.3) 1119 (77.0) NS Divorced 46 (3.2) 56 (3.9) Widow 162 (11.1) 137 (9.4) Residency Urban 1005 (69.2) 1100 (75.7) 10-3 Rural 448 (30.8) 353 (24.3) Educational level Illiterate 918 (63.2) 729 (50.2) Primary 274 (18.9) 272 (18.7) 10-3 Secondary 175 (12.0) 267 (18.4) Higher 86 (5.9) 185 (12.7) Monthly household < (82.6) 1044 (71.9) income (MAD)* (14.0) 289 (19.9) 10-3 > (3.4) 120 (8.3) Smoking status Never smokers 1127 (77.6) 1217 (83.8) Ex-smokers 150 (10.3) 146 (10.0) 10-3 Smokers 176 (12.1) 90 (6.2) * 1 MAD 0.11$

[95% IC] OR a [95% IC] OR b [95% IC] OR a [95% IC] OR b [95% IC] OR a [95% IC] Industrial

56 [0.46-0.69] 0.71 [0.55-0.91] Yogurt 0.42 [0.32-0.55] 0.57 [0.40-0.82] 0.47 [0.36-0.61] 0.

58 [0.46-0.74] 0.80 [0.58-1.08] 0.65 [0.55-0.76] 0.75 [0.61-0.

[0,57-1,21] 0,66 [0,53-0,83] 0,75 [0,57-0,98] Raib 0,75 [0,59-0,95] 0,78 [0,57-1,05] 0,61

7 Table 2. Adjusted Odds Ratio for dairy products consumption in CRC cases and controls by CRC subtypes. Dairy products Colon cancer (N=729) Rectal cancer (N=724) Colorectal cancer (N=1453) OR b [95% IC] OR a [95% IC] OR b [95% IC] OR a [95% IC] OR b [95% IC] OR a [95% IC] Industrial dairy products Milk 0.53 [ ] 0.68 [ ] 0.59 [ ] 0.69 [ ] 0.56 [ ] 0.71 [ ] Yogurt 0.42 [ ] 0.57 [ ] 0.47 [ ] 0.74 [ ] 0.44 [ ] 0.66 [ ] Cheese 0.71 [ ] 0.68 [ ] 0.58 [ ] 0.80 [ ] 0.65 [ ] 0.75 [ ] Traditional dairy products Lben 0,60 [0,44-0,82] 0,64 [0,43-0,96] 0,74 [0,54-0,99] 0,83 [0,57-1,21] 0,66 [0,53-0,83] 0,75 [0,57-0,98] Raib 0,75 [0,59-0,95] 0,78 [0,57-1,05] 0,61 [0,48-0,78] 0,66 [0,48-0,91] 0,68 [0,57-0,81] 0,72 [0,58-0,90] Saykok 0,67 [0,54-0,84] 0,70 [0,53-0,93] 0,66 [0,52-0,82] 0,59 [0,45-0,78] 0,67 [0,57-0,78] 0,64 [0,52-0,77] Jben 0,44 [0,33-0,59] 0,46 [0,32-0,66] 0,50 [0,38-0,67] 0,57 [0,39-0,81] 0,47 [0,39-0,58] 0,52 [0,40-0,67] Lben Raib Saikok Jben

cancer Colorectal cancer ORb [95% IC] ORa [95% IC] ORb [95% IC] ORa [95% IC] ORb [95% IC] ORa[95% IC] Total meat Non-intake 1

12) Red meat Non-intake 1 1 1 1 1 1 Intake 1.92(1.49-2.47) 1.95(1.44-2.66) 1.48(1.15-1.91) 1.55(1.11-2.17) 1.70(1.42-2.04) 1.

8 Table 4. Adjusted OR for meat consumption and CRC cancer in Morocco: case-controls study (1453cases/1453controls) Colon cancer Rectal cancer Colorectal cancer ORb [95% IC] ORa [95% IC] ORb [95% IC] ORa [95% IC] ORb [95% IC] ORa[95% IC] Total meat Non-intake Intake 1.95( ) 2.18( ) 1.41( ) 1.27( ) 1.68( ) 1.68( ) Red meat Non-intake Intake 1.92( ) 1.95( ) 1.48( ) 1.55( ) 1.70( ) 1.63( ) White meat Non-intake Intake ( ) ( ) ( ) ( ) ( ) ( ) Unadjusted odds ratio All odds ratios and their corresponding 95% confidence intervals were calculated by performing conditional logistic regressions Adjusted for age, Residence; Smoking status; Alcohol intake; Physical activity; Body mass index; Education levels; Level of income Family history of CRC ; Dairy products; Fruits; Vegetables; Fibre; Calcium;;Energy intake.

case-controls study (1453 case/1453 controls) Khlii of beef Colon cancer Rectal

OR b [95% IC] OR a [95% IC] Non-intake 1 1 1 1 1 1 Khlii of lamb Intake 0.

71(0.47-1.06) Non-intake 1 1 1 1 1 1 Intake 0.23(0.90-0.63) 0.17(0.05-0.52) 1.

72) Quaddid Non-intake Intake Delicatness meat Non-intake Intake 1 0.54(0.33-0.

9 Table 5. Adjusted OR for processed meat consumption and CRC cancer in Morocco case-controls study (1453 case/1453 controls) Khlii of beef Colon cancer Rectal cancer Colorectal cancer OR b [95% IC] OR a [95% IC] OR b [95% IC] OR a [95% IC] OR b [95% IC] OR a [95% IC] Non-intake Khlii of lamb Intake 0.69( ) 0.59( ) 0.80( ) 0.76( ) 0.75( ) 0.71( ) Non-intake Intake 0.23( ) 0.17( ) 1.92( ) 0.66( ) 0.39( ) 0.37( ) Quaddid Non-intake Intake Delicatness meat Non-intake Intake ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( )

[95%IC] N=729 Rectal cancer ORa [95%IC] N=724 CRC overall ORa [95%IC] N=1453 Body

34-0.75] 0.45 [0.29-0.68] 0.48 [0.36-0.63] Physical activity <0.5 1 1 1 0.5-<1 0.56 [0.

24-0.45] Plant foods <0.5 1 1 1 0.5-<1 0.47 [0.21-1.04] 0.34 [0.13-0.88] 0.41 [0.22-0.

10 Table 6. Adherence to WCRF/AICR recommendations and CRC risk in Morocco Colon cancer ORa [95%IC] N=729 Rectal cancer ORa [95%IC] N=724 CRC overall ORa [95%IC] N=1453 Body fatness < < [ ] 0.46 [ ] 0.59 [ ] [ ] 0.45 [ ] 0.48 [ ] Physical activity < < [ ] 0.34 [ ] 0.44 [ ] [ ] 0.24 [ ] 0.33 [ ] Plant foods < < [ ] 0.34 [ ] 0.41 [ ] [ ] 0.15 [ ] 0.21 [ ] Alcoholic drinks < < [ ] 0.37 [ ] [ ] 1.07 [ ] 0.96 [ ]

11 Conclusion Increasing incidence of CRC (Even if still among the lowest) First national and large study in Morocco and MENA region Same known nutritional risk factors Some Moroccan specificities studied for the first time Other needed studies ( Extension of the EPIC to APIC study for example) More accurate results International comparisons Adaptation of the international recommendations to the local context

12 Acknowledgments Fez City The spiritual and scientific capital of Morocco

13 Nutrient profiling and cancer risk results from the EPIC study as an example for future public health strategies Inge Huybrechts Track 1 - Motivating prevention and healthy behaviours Disclosure of interest: no conflicts of interests to declare 1

authorities consider the implementation of a simplified labelling system to reflect the

14 Background Figure1. Nutri-Score Helping consumers make healthier food choices key to prevention of cancer Political authorities consider the implementation of a simplified labelling system to reflect the nutritional quality of food products Nutrient profiling is a scientific method for assessing the nutritional quality of foods & beverages can be used to promote public health dietary goals

15 The Nutri-Score A five-colour nutrition label derived from the Nutrient Profiling System of the British Food Standards Agency (FSAm-NPS) Calculated for each food/beverage using its 100g-content in: energy sugar saturated fatty acids sodium fibres proteins fruits/vegetables/legumes/nuts Figure1. Nutri-Score

16 The Nutri-Score In 2017, the Nutri-Score was selected as official front-ofpack nutrition label to be implemented in France In 2018, discussions regarding the possible implementation of a unique nutrition labelling system for all EU countries were initiated Similar discussions are ongoing in North & South Americas, Canada and Australia Scientific evidence regarding the relevance of this label at an international level is important Figure1. Nutri-Score

17 Figure1. Nutri-Score Nutri-Score & cancer risk in Europe Validity & health impact assessment of the Nutri-Score as underlying nutrient profiling system for front-of-pack nutrition labels is needed Associations between the individual Nutri-Score and cancer risk investigated in the large and diverse European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

The EPIC-study Multi-centre cohort 521,448 volunteers Recruited from 1992 to 2000 10 European countries Dietary questionnaires Lifestyle questionnaires

18 The EPIC-study Multi-centre cohort 521,448 volunteers Recruited from 1992 to European countries Dietary questionnaires Lifestyle questionnaires Biospecimen (e.g. metabolites, GWAS) Health outcomes (e.g. via cancer registries, health insurance records) Food composition & occurrence data Source: 6

19 Computation of Nutri-Score Higher score lower nutritional quality

20 Associations between Nutri-Score & cancer risk Multivariable Cox proportional hazards models, EPIC FSAm-NPS Dietary Index* range (men/women) n=471,495 *Higher score lower nutritional quality Per 2-point increment Q5 vs. Q1 P-trend Total cancer All (cases/person-years) 49,794/6,635,062 Sex-adjusted model - HR (95% CI) 1.04 ( ) 1.12 ( ) <0.001 Multi-adjusted model - HR (95% CI) 1.02 ( ) 1.07 ( ) <0.001 Colorectal cancer All (cases/person-years) 5,806/6,639,343 Sex-adjusted model - HR (95% CI) 1.03 ( ) 1.11 ( ) 0.03 Multi-adjusted model - HR (95% CI) 1.03 ( ) 1.11 ( ) 0.03 Breast cancer Women (cases/person-years) 12,063/4,659,777 Unadjusted model - HR (95% CI) 1.03 ( ) 1.08 ( ) 0.01 Multi-adjusted model - HR (95% CI) 1.02 ( ) 1.06 ( ) 0.05

21 Associations between Nutri-Score & health Weight gain in men (SU.VI.MAX) +16% risk for becoming obese for 1 point increase in Nutri-score +91% risk for becoming obese (Q4 vs. Q1) Figure1. Nutri-Score Metabolic syndrome (SU.VI.MAX) +43% risk of developing MetS (Q4 vs. Q1) Cardiovascular disease (NutriNet-Sante & SU.VI.MAX) +40 to +61% risk of CVD (Q4 vs. Q1) Cancer (SU.VI.MAX & NutriNet-Sante ) Overall cancer: +7 to +34% risk (Q5 vs. Q1) Breast cancer: +52% risk (Q5 vs. Q1) Julia, Kesse-Guyot et al., Prev Med 2015;81: Julia, Kesse-Guyot et al., J Nutr, 2015;145(10): Deschasaux, Touvier et al., BMJ Open. 2017;7(6):e Adriouch, Fezeu, Touvier et al., Int J Cardiol. 2017;234:22-27 Adriouch, Fezeu, Touvier et al., Eur J Prev Cardiol. 2016;23(15): Donnenfeld, Touvier et al, BJN 2015;1-9 9

22 Associations between Nutri-Score & health risk in Europe The consumption of food products with a higher Nutrient Profiling Score (lower nutritional quality) was associated with a higher disease risk (incl. cancer, obesity, metabolic syndrome, CVD) This supports the relevance of the Nutri-Score as underlying nutrient profiling system for front-of-pack nutrition labels in the prevention of NCD such as cancer Figure1. Nutri-Score

procedure for systematic validation and comparison of different approaches is required WHO has developed a Guiding

23 WHO Nutrient profiling project Development of an internationally recognized method for nutrient profiling? beneficial for a number of applications criteria might not be applicable to all cultures, settings and applications A procedure for systematic validation and comparison of different approaches is required WHO has developed a Guiding Principles and Framework Manual to assist member states in developing or adapting NP models.

24 Acknowledgements Nutritional Epidemiology Research Team (EREN), Paris Mélanie Deschasaux Chantal Julia Serge Hercberg Mathilde Touvier International Agency for Research on Cancer (IARC), Lyon Neil Murphy Marc Gunter Pietro Ferrari Corinne Casagrande Contact: 12

25 13

26 Take home messages Specificity of nutrition-related exposures and local environment are different in LMIC than in Westernized populations More local research is needed, as cancer risk factors and subtypes may not be the same in LMIC than in HIC Prospective investigations into cancer and nutrition are needed (e.g. EPIC APIC)

27 Take home messages Use local resources, expertise and collaborations Recommendations for cancer prevention may need to be adapted and tailored for LMIC Feasibility and impact of public health strategies shown to be effective in HIC should be evaluated in LMIC (e.g. Nutrient Profiling as Front-of-Package)

28 Priorities in LMIC? Discussion Unutilised potentials in LMIC? Nutrition transition Opportunities in LMIC?

29 Understanding global nutrition habits and dynamics as a step towards cancer prevention and control Aim: Nutrition-related factors of common cancers in HIC Nutrition-related factors in LMIC? Future public health strategies

30 Ellen Kampman, PhD Nutrition and Disease Wageningen University, The Netherlands

31 Phyllis Ngunjiri s questions Why is the incidence of Western cancers in Africa and other LMICs increasing? Are risk factors of cancer in LMICs similar to HICs? Why is breast cancer occurring in younger women in Africa? Is obesity a risk factor for breast cancer in Africa? What can we do to prevent cancer in LMICs?

32 Global cancer incidence

33 Predicted global cancer cases Economic progress Increase in life expectancy Urbanisation Adaptation to Western lifestyles

34 Transition to Western dietary habits in LMICs

35 Transition to Western physical activity habits in LMICs

36 Transition in spectrum of common cancer in LMICs breast, colorectal & prostate reproductive hormonal lifestyle cervical & liver infections Based on Brady et al Lancet 2012

37 Dietary guidelines for cancer prevention

38 Are these global recommendations?

39 Cancer in LMIC: are risk factors similar?

40 Is cancer similar? Age at diagnosis of breast cancer From Knaul FM et al. Int J Gynecol Obstetrics 2012

41 Due to different demographic structure? From: Akarolo-Anthony SN, et al. Emerging breast cancer epidemic: evidence from Africa. Breast Cancer Res. 2010

42 Mostly pre-menopausal breast cancer in Africa Same etiology?

43 Risk factors for premenopausal breast cancer in South Africa and Latin America Sabina Rinaldi, PhD Nutrition and Metabolism International Agency for Research on Cancer (IARC), Lyon, France

44 Colorectal cancer more common in Northern Africa Colon cancer incidence by age and sex, Morocco, Casablanca cancer registry

45 Nutrition and CRC risk: strong evidence in HICs

46 Nutritional risk factors of colorectal cancer in Morocco Karima El Rhazi, MD, PhD Epidemiology & Community Medicine Faculty of Medicine Sidi Mohamed Ben Abdillah University Fez, Morocco

48 From EPIC to APIC? What do we need? Good infrastructure Cancer registries Trained researchers??

49 Nutrient profiling and cancer risk results from the EPIC study as an example for future public health strategies Inge Huybrechts, PhD Nutrition and Metabolism International Agency for Research on Cancer(IARC), Lyon, France

Programme 9.30-9.40 Welcome and aim of the workshop 9.40-9.50 Nutrition and breast & colorectal cancer in HIC 9.50-10.10 Nutrition and breast cancer in Latin America and South Africa 10.10-10.

50 Programme Welcome and aim of the workshop Nutrition and breast & colorectal cancer in HIC Nutrition and breast cancer in Latin America and South Africa Nutrition and colorectal cancer in Morocco Nutrition profiling and cancer risk: future public health strategies Summarizing and points for discussion Discussion Ellen Kampman Sabina Rinaldi Karima El Rhazi Inge Huybrechts

51 In honour of Mrs. Phyllis Ngunjiri Nairobi, Kenya 25 February August 2016

Breast Cancer The PRECAMA Study. Dr. Isabelle Romieu Head, Section of Nutrition and Metabolism

Breast Cancer The PRECAMA Study Dr. Isabelle Romieu Head, Section of Nutrition and Metabolism Estimated incidence of breast cancer (2008) Age- standardised rates per 100,000 GLOBOCAN 2008 (globocan.iarc.fr)