Gaetano Crepaldi CNR Sezione Invecchiamento-Padova Nutrizione e cancro Gaetano Crepaldi CNR Sezione Invecchiamento-Padova

L’alimentazione è responsabile di un terzo dei tumori

Mediterranean Diet Score Gli alimenti vengono suddivisi in gruppi: un gruppo racchiude tutti quelli che sono considerati protettivi (verdure, legumi, frutta e mandorle, cereali, pesce e frutti di mare, olio di oliva, moderato consumo di vino); un altro gruppo racchiude gli alimenti considerati meno benefici (carne e prodotti a base di carne, latticini). Si assegna un punteggio alla quantità e alla frequenza con la quale vengono consumati: un punteggio basso, da 0 a 6, è indicativo di una bassa aderenza alla Dieta Mediterranea (0 nessuna, e via via aumentando); da 7 a 10 una media aderenza; da 11 a 18 un’alta aderenza (massima per un punteggio di 18). 4

The Mediterranean Diet Score Components beneficial for health Vegetables Legumes Fruits and nuts Fish and seafood Cereals High ratio of monounsaturates to saturates Components not beneficial for health Meat and products Dairy products Value=1, if consumption ≥ sample median Value =0, if consumption < sample median Value=0, if consumption ≥ sample median Value =1, if consumption < sample median

The Mediterranean Diet Score (ctd) Ethanol MEN WOMEN Value=1, if 10g (one unit) ≤ consumption/day < 50 g (six units) Value =0, otherwise Value=1, if 5g (half a unit) ≤ consumption/day < 25 g (three units) Value =0, otherwise

Perché è importante costruire uno score? Uno score riassume più associazioni attraverso una singola variabile; cattura tutte le dimensioni (anche gli estremi) dello stile alimentare d’interesse; prende in considerazione possibili effetti di confondimento o di modificazione

Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of all-cause mortality. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of all-cause mortality. The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of information from the study. The diamond indicates pooled estimates. Francesco Sofi et al. Am J Clin Nutr 2010;92:1189-1196 ©2010 by American Society for Nutrition

Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of mortality from or incidence of cardiovascular diseases. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of mortality from or incidence of cardiovascular diseases. The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of information from the study. The diamond indicates pooled estimates. CHD, coronary heart disease. Francesco Sofi et al. Am J Clin Nutr 2010;92:1189-1196 ©2010 by American Society for Nutrition

Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of mortality from or incidence of neoplastic diseases The center of each square indicates the relative risk of the study, and the horizontal ... Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of mortality from or incidence of neoplastic diseases The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of the information from the study. The diamond indicates pooled estimates. Francesco Sofi et al. Am J Clin Nutr 2010;92:1189-1196 ©2010 by American Society for Nutrition

Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of incidence of neurodegenerative diseases. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of incidence of neurodegenerative diseases. The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of the information from the study. The diamond indicates pooled estimates. Francesco Sofi et al. Am J Clin Nutr 2010;92:1189-1196 ©2010 by American Society for Nutrition

European Prospective Investigation for Cancer and nutrition (EPIC) Prospective cohort study (1992 - To investigate the role of biologic, dietary, lifestyle and environmental factors in the etiology of cancer and other chronic diseases. 23 research centers in 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden and the UK) Study sample: general population of specific geographical areas Coordinated by IARC and supported by the EC.

EPIC – Greece (baseline data collection) 28 572 participants, recruited between 1994 and 1999. Dietary data: interviewer administered, semi-quantitative food-frequency questionnaire Socio-demographic and lifestyle characteristics questionnaire (incl. smoking habits, physical activity and use of dietary supplements) Somatometric measurements

EPIC – Greece (follow-up) Active follow-up through telephone interviews A structured form is filled-in Verification of diagnosis accomplished through pathology reports, medical records, discharge diagnoses or death certificates

Study sample Median follow-up time: 7.9 years 851 cases of incident cancer (excluding non-melanoma skin cancer) 10% of initial cohort excluded due to: prevalent cancer at enrolment (excluding non-melanoma skin cancer), lack of information from follow-up and missing values

Distribution of incident cancer cases Cancer site ICD-O-2 codes Men Women Stomach C16 35 13 Large bowel C18-21 38 Liver C22 19 9 Pancreas C25 18 17 Lung C34 116 Hematopoietic system C42 25 Breast C50 158 Cervix uteri C53 - 21 Corpus uteri C54 15 Ovary C56 34 Prostate C61 48 Kidney C64 7 Bladder C67 27 Brain C71 11 14 Thyroid gland C73 2 Lymphomas C77 16 All other sites 50 30 Total 421 430 Source: Benetou V et al. Conformity to traditional Mediterranean diet and cancer incidence. Br J Cancer. 2008;99(1):191-5.

Statistical analysis To assess the relation of dietary components or MD score to cancer incidence Models adjusted for age, years of schooling, smoking status, body mass index, physical activity, ethanol intake Stratification by sex

Hazard ratios for incident cancer per increments of intake Intake (g/day) Increment Hazard ratio 95% CI Vegetables 230 0.96 0.88 to 1.05 Legumes 6 0.98 0.92 to 1.05 Fruits – including nuts 205 1.01 0.93 to 1.09 Dairy products 140 1.03 0.96 to 1.10 Cereals 60 0.91 to 1.05 Meat 50 1.08 0.99 to 1.17 Fish 15 0.99 to 1.08 Ratio MUFA to SFA 0.5 0.91 0.85 to 0.98 Olive oil 20 0.97 0.91 to 1.04 Ethanol 10 1.00 0.96 – 1.04 Eggs 1.07 1.01 to 1.13 Energy intake (kcal/day) 650 1.05 0.98 to 1.14 Source: Benetou V et al. Conformity to traditional Mediterranean diet and cancer incidence. Br J Cancer. 2008;99(1):191-5.

Hazard ratios for incident Ca per Mediterranean diet score Category of the Mediterranean diet score Hazard ratios Score 0-3 Score 4-5 Score 6-9 per 2-point increment For any cancer Ref. 0.84 (0.72 to 0.98) 0.78 (0.64 to 0.94) 0.88 (0.80 to 0.95) Smoking related Ca 0.83 (0.67 to 1.03) 0.86 (0.66 to 1.11) 0.91 (0.81 to 1.02) Smoking unrelated Ca (0.68 to 1.08) 0.70 (0.52 to 0.93) (0.74 to 0.95) Excluding 1st year of FU (all cancers) 0.85 (0.72 to 1.00) 0.76 (0.63 to 0.93) (0.80 to 0.96) By sex Men 0.96 (0.76 to 1.20) (0.63 to 1.09) (0.80 to 1.02) Women 0.74 (0.59 to 0.92) 0.73 (0.56 to 0.96) Source: Benetou V et al. Conformity to traditional Mediterranean diet and cancer incidence. Br J Cancer. 2008;99(1):191-5.

Perchè la DM è associata negativamente al rischio di cancro, anche se l’associazione delle singole componenti non risulta significativa? Ciascuna componente, considerata da sola, potrebbe avere piccoli effetti, non rilevabili singolarmente; potrebbero esistere interazioni di natura biologica tra alcune componenti della Dieta Mediterranea; uno score di aderenza alla Dieta Mediterranea può valutare anche gli estremi dell’esposizione cumulativa; l’effetto del “caso” è maggiormente rilevante quando si analizza un singolo cibo, rispetto a quando si considerano diverse componenti contemporaneamente come in uno score.

Perchè gli scores sembrano essere inversamente associati agli eventi patologici nei paesi Mediterranei e non così fortemente in altre parti del mondo? Grandi quantità di frutta fresca e con guscio, vegetali, legumi, e olio extravergine di oliva sono consumati da una larga fetta della popolazione nei paesi Mediterranei, ma da una relativamente bassa percentuale di popolazione nei paesi non-Mediterranei Nei paesi Mediterranei l’alcol è rappresentato prevalentemente dal vino e consumato durante il pasto.

Mandair et al. Nutrition & Metabolism 2014, 11:30

Allen NE, et al

PROSTATE CANCER Schwingshackl et al,

Prevenzione – Tumore della Prostata C’è qualche evidenza descrittiva che suggerisce un possibile ruolo della Dieta Mediterranea come fattore di protezione del tumore della prostata E, queste evidenze sono utili per generare ipotesi per studi clinici 27

Prevenzione – Tumore della Prostata Comunque, la Dieta Mediterranea è sicuramente efficace nel prevenire altre forme di tumore, malattie cardiovascolari, diabete, disturbo cognitivo, QUINDI, Nutrizione adeguata ed esercizio fisico vanno consigliati senza alcun dubbio, perchè contribuiscono al nostro invecchiamento di successo 28