COLTIVAZIONE COLTIVAZIONE DELL’OLIVODELL’OLIVO

• Origini: 5000 a.C. (Medio

Oriente)

• 4500 a.c. Codice di

Hammurabi

• In Italia: 500 a.c.

• 800 milioni di piante nel

mondo

• 700 milioni di piante nel

Mediterraneo

Mediterranean Mediterranean DietDiet

Dietary patterns found in olive growing regions

of the Mediterranean Countries

Basso rischio cardiovascolare

Basso rischio di cancro

“Vantaggio” Mediterraneo

RUOLO DELL’OLIO D’OLIVA

IMPORTANZA BIOLOGICA IMPORTANZA BIOLOGICA DELL’OLIO D’OLIVADELL’OLIO D’OLIVA

• MUFA- Fluidità di membrana

cellulare

• ANTIOSSIDANTI- Anti radicali liberi- Anti perossidazione

• MALATTIE CARDIOSVACOLARI- LDL - colesterolo- Ipertrigliceridemia

IMPORTANZA BIOLOGICA IMPORTANZA BIOLOGICA DELL’OLIO D’OLIVADELL’OLIO D’OLIVA

• APPARATO DIGERENTE- attività della colecisti- secrezione pancreatica

• CANCRO- > apoptosi - oncogene ras,- < addotti al DNA

< 10% PROSTATE,

PANCREAS, ENDOMETRIUM

< 25% COLON

< 15% BREAST

WITH MEDITERRANEAN DIET:

(Trichopoulou et al., 2000)

CANCER RISK FACTORSCANCER RISK FACTORSCANCER RISK FACTORSCANCER RISK FACTORS

The issue of fats, and of specific types of fats, on the risk of colorectal and breast cancers, as well as of several other neoplasms, remains a major open question.

FATSFATS

RRs and 95% CI of selected cancers according to RRs and 95% CI of selected cancers according to RED MEATRED MEAT consumption. Italy, 1983-1997 consumption. Italy, 1983-1997

Pesce

1

1.2

1.4

1.6

1.8

0.8

0.6

Carni bianche

Carni lavorate Carni

rosse

Tutte le carni

Cohort studies

Case-control studies All studies

CARNE & CANCRO DEL COLON

Meta-analisi, IARC, Lione 2002

CARNE & CANCRO DEL COLON

Meta-analisi, IARC, Lione 2002

GENETICA E DIETA

Nei Giapponesi emigrati negli Stati Uniti:

Marcato aumento del cancro del colon in soggetti con genotipo rapid NAT2:

Ma solo in chi consumava carni rosse molto cotte

J Natl Cancer Inst Monogr 1999;(26):101-5COMBINED INFLUENCE OF GENETIC AND DIETARY FACTORS ON COLORECTAL CANCER INCIDENCE IN JAPANESE AMERICANS.Marchand LL. (Honolulu, USA)

Cancer Epidemiol Biomarkers Prev 2002 Jun;11(6):541-8DIET ACTIVITY, AND LIFESTYLE ASSOCIATIONS WITH P53 MUTATIONS IN COLON TUMORS. Slattery ML, Curtin K et al. (Salt Lake City, USA)

P53: tumor suppressor gene

Casi con mutazione del gene P53 più frequentemente:

consumano una dieta “occidentale”

presentano indice glicemico alto

seguono una dieta ricca in carni rosse e fast food

GRASSI N-6 E N-3 GRASSI N-6 E N-3 IN RAPPORTO TRA IN RAPPORTO TRA

ACIDI VARIE ACIDI VARIE POPOLAZIONIPOPOLAZIONI

POPOLAZIONI n-6:n-3

Periodo paleolitico 0,79

Grecia prima del 1960 1,00 / 2,00

Stati Uniti 2000 16,74

Regno Unito e Nord Europa 15

Giappone 4

Italia 13

RRs and 95% CI of selected cancers according to RRs and 95% CI of selected cancers according to FISHFISH consumption. Italy, 1983-1997. consumption. Italy, 1983-1997.

N-3 Polyunsaturated fatty acidsN-3 Polyunsaturated fatty acidsQUINTILE OF INTAKE

CANCER SITE CASES/CONTROLS (N)

3RD 5TH (HIGHEST)

Oral cavity/pharynx

736/1772 0.7 (0.5-0.9) 0.5 (0.3-0.7)

Oesophagus 395/1066 0.7 (0.5-1.1) 0.5 (0.3-0.7)

Large bowel 2280/4765 1.0 (0.9-1.2) 0.7 (0.6-0.9)

Colon 1394/4765 0.9 (0.8-1.1) 0.7 (0.5-0.8)

Rectum 886/4765 1.1 (0.9-1.4) 0.8 (0.6-1.0)

Breast 2900/3122 1.0 (0.8-1.1) 0.8 (0.7-1.0)

Ovary 1031/2411 0.8 (0.6-1.0) 0.6 (0.4-0.7)

OMEGA-3 & CANCROOMEGA-3 & CANCRO

(olio di pesce)(olio di pesce)

DHADHA

Riduce l’espressione di Riduce l’espressione di COX-2 COX-2 Induce Induce apoptosiapoptosi

(Da Caterina,01)(Da Caterina,01)

Olive oil & Olive oil & Colorectal cancerColorectal cancer

Tertile of intake

2 3 (high)

Colorectal 0.78 (0.62-0.99) 0.77 (0.59-0.99)

Colon 0.79 (0.59-1.04) 0.82 (0.60-1.12)

Rectum 0.79 (0.57-1.11) 0.69 (0.46-1.02)

In a large study from Italy, isocaloric substitution of 5% of total calories as

saturated fats by unsaturated ones was associated with reductions in breast (OR= 0.67) and colorectal (OR= 0.78) cancer risk

FATSFATS

FATSFATS

DIETARY CHANGE BREAST (OR 95% CI)

COLON RECTUM

(OR 95% CI)

Replacement of saturated fat by complex carbohydrate

(10% of cal.)

0.95

(0.73-1.25)

0.96

(0.74-1.24)

Replacement of saturated fat by polyunsaturated fat

(5% of cal.)

0.67

(0.54-0.83)

0.78

(0.65-0.95)

Replacement of complex carbohydrate by polyunsaturated fat

(5% of cal.)

0.69

(0.58-0.81)

0.80

(0.69-0.93)

FATSFATS

DIETARY CHANGE BREAST (OR 95% CI)

COLON RECTUM

(OR 95% CI)

Replacement of saturated fat by monounsaturated fat

(5% of cal.)

0.91

(0.73-1.12)

0.89

(0.73-1.09)

Replacement of complex carbohydrate by monounsaturated fat

(5% of cal.)

0.93

(0.83-1.04)

0.91

(0.82-1.00)

Olive oil Olive oil Oral and pharyngeal Oral and pharyngeal cancercancer

UPPER LIMIT - (g per day) INTAKE QUINTILE

1 3 5

Olive oil 3.2 29.5 -

OR (95% CI) 1 0.7 (0.5-1.1) 0.4 (0.3-0.7)

Vegetable-adjusted OR (95% CI) 1 0.8 (0.5-1.2) 0.6 (0.4-0.9)

Mixed seed oils 0.3 2.3 -

OR (95% CI) 1 1.0 (0.7-1.4) 1.1 (0.7-1.7)

Vegetable-adjusted OR (95% CI) 1 0.9 (0.6-1.4) 1.1 (0.7-1.7)

Butter 0.4 1.9 -

OR (95% CI) 1 1.3 (0.8-1.9) 2.3 (1.6-3.5)

Vegetable-adjusted OR (95% CI) 1 1.3 (0.9-2.0) 2.4 (1.6-3.5)

Substituting Substituting olive oil olive oil for other seasoning for other seasoning fatsfats has favourable has favourable

effects on the risk of effects on the risk of oral, laringeal and oral, laringeal and

pharyngeal (OR= 0.7),pharyngeal (OR= 0.7), and and oesophageal oesophageal (OR= 0.4)(OR= 0.4) cancers cancers

FATS

Mediterranean diet Mediterranean diet score and cancers score and cancers

of the upper of the upper digestive tractdigestive tract

An a priori defined score, summarising eight of the major characteristics of the

Mediterranean diet, was applied to data of case-control studies of oral (n=599),

oesophageal (n=304) and laryngeal (n=460) cancers

Diet and cancers of the

upper digestive tract

CANCER, OR (95% CI)

ORAL/PHARYNGEAL OESOPHAGEAL LARYNGEAL

Monounsaturated/

saturated fat ratio

0.72 (0.56-0.93) 0.73 (0.51-1.01) 0.97 (0.73-1.28)

Alcohol 4.26 (3.11-5.83) 6.04 (3.79-9.62) 2.77 (2.01-3.83)

Legumes 1.09 (0.87-1.38) 1.03 (0.74-1.42) 0.75 (0.58-0.98)

Cereals 0.77 (0.59-1.00) 0.96 (0.67-1.38) 0.92 (0.68-1.24)

Fruit 1.06 (0.83-1.35) 0.95 (0.68-1.31) 0.82 (0.62-1.07)

Vegetables 0.79 (0.62-1.01) 0.72 (0.51-1.01) 0.51 (0.39-0.67)

Meat and meat products 1.42 (1.11-1.81) 1.50 (1.06-2.13) 1.53 (1.15-2.04)

Milk and dairy products 1.09 (0.86-1.40) 1.24 (0.87-1.75) 1.07 (0.81-1.42)

Cancer Mediterranean diet score<3 4 6

Oral/pharyngeal

Cases/controls 214/241 120/376 41/201

OR (95% CI) 1 0.41 (0.30-0.57) 0.40 (0.26-0.62)

Oesophageal

Cases/controls 102/147 66/174 14/83

OR (95% CI) 1 0.63 (0.41-0.95) 0.26 (0.13-0.51)

Laryngeal

Cases/controls 183/225 98/279 19/124

OR (95% CI) 1 0.47 (0.33-0.66) 0.23 (0.13-0.40)

Mediterranean diet score and cancers of the

upper digestive tract (Bosetti, ‘03)

Pizza and cancer risk

Pizza is one of the best known and most widespread Italian foods, and it is the most common generic commercial sign worldwide. Investigating the role of pizza on cancer risk may have interesting implications in respect to dietary advice not only in Italy

Pizza and cancer riskPizza and cancer risk

CANCER

OR (95% CI)

OCCASIONAL REGULAR ALL EATERS

Oral cavity and pharynx

0.76 (0.60-0.95) 0.66 (0.47-0.93) 0.73 (0.59-0.91)

Oesophagus 0.57 (0.42-0.78) 0.41 (0.25-0.69) 0.53 (0.39-0.72)

Larynx 0.86 (0.66-1.11) 0.82 (0.56-1.19) 0.85 (0.66-1.08)

Colon 0.84 (0.72-0.97) 0.74 (0.61-0.89) 0.81 (0.70-0.93)

Rectum 0.85 (0.71-1.02) 0.93 (0.75-1.17) 0.88 (0.74-1.04)

Cancer Causes Control 2000 Aug;11(7):609-15MEN WHO CONSUME VEGETABLE OILS RICH IN MONOUNSATURATED FAT: THEIR DIETARY PATTERNS AND RISK OF PROSTATE CANCER (NEW ZEALAND).Norrish AE, Jackson RT et al. (Auckland, New Zealand)

317 prostate cancer cases vs 480 controls.

Increasing levels of MUFA-rich vegetable oil intake were associated with a progressive reduction in prostate cancer risk - multivariate relative risk = 0.5 (> 5.5 ml per day vs. nonconsumption - P trend = 0.005)

Prostate cancer risk was not associated with intake of total MUFA or the major animal food sources of MUFA

CONCLUSION: 1) protective effect of an associated dietary pattern high in antioxidants and fish oils.

2) Independent protective effect of MUFA-rich vegetable oils unrelated to the MUFA

component

PHENOLIC AND LIPID COMPONENTS OF OLIVE OILS-2:

THE CONCENTRATION AND ANTIOXIDANT ACTIVITY OF TOTAL

PHENOLS, SIMPLE PHENOLS, SECOIRIDOIDS, LIGNANS AND

SQUALENE.   

Robert W. Owen,1 Attilio Giacosa,2

Walter Mier, Bertold Spiegelhalder1 and Helmut

Bartsch1

 

1German Cancer Research Center, Heidelberg, Germany

 2National Institute of Cancer Research, Genoa, Italy

   

TOTAL AND INDIVIDUAL PHENOLIC TOTAL AND INDIVIDUAL PHENOLIC COMPOUNDS IN OLIVE OILCOMPOUNDS IN OLIVE OIL

PHENOLIC COMPOUND mg/kg

OLIVE OIL

ALL VOQ RVO P value

Total 196 19 232 15 62 12 < 0.0000

1

Hydroxytyrosol 11.66 2.60

14.42 3.01

1.74 0.84

< 0.05

Tyrosol 22.13 3.82

27.45 4.05

2.98 1.33

< 0.01

Total simple phenols (TSP)

33.79 4.48

41.87 6.17

4.72 2.15

< 0.01

SID-1 7.97 2.57

9.62 3.18

2.00 0.87

ns

SID-2 15.75 3.54

18.09 4.31

7.30 3.01

ns

Total secoiridoids (SID)

23.71 5.61

27.72 6.84

9.30 3.81

ns

Lignans 34.09 4.42

41.53 3.93

7.29 2.56

< 0.001

TSP + SID + LIGNANS

91.59 10.57

111.12 9.99

21.31 8.03

< 0.001

POLYPHENOLSPOLYPHENOLS

0

50

100

150

200

250

300

350

Extra-verginRefined Seed oil

LIGNANSLIGNANS

0

10

20

30

40

50

60

70

80

90

Extra-vergin Refined Seed oil

Eur J Cancer Prev 2002 Aug;11(4):351-8Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis.Fabiani R, De Bartolomeo A, Rosignoli P, Servili M, Montedoro GF, Morozzi G. (Perugia, Italy)

Hydroxytyrosol inhibited proliferation of both human promyelocytic leukaemia cells HL60 and colon adenocarcinoma cells HT29

At concentrations ranging from 50 to 100 micromol/l, hydroxytyrosol induced an appreciable apoptosis

Hydroxytyrosol (50-100 micromol/l) arrested the cells in the G0/G1 phase with a concomitant decrease in the cell percentage in the S and G2/M phases.

Scavenging of ROS generated in the faecal matrix Scavenging of ROS generated in the faecal matrix by tyrosol isolated from olive oil.by tyrosol isolated from olive oil.

100

20 0.01 0.1 1 10 100 1000

10000

Dihydroxy benzoic acids (%)

Tyrosol (µ M)

J Agric Food Chem 2002 Oct 9;50(21):5962-7Influence of thermal treatments simulating cooking processes on the polyphenol content in virgin olive oil.Brenes M, Garcia A, Dobarganes MC et al. (Sevilla, Spain)• Thermal oxidation:

– rapid degradation of alpha-tochopherol– 180°: < tyrosol and tydroxytyrosol

for 25 h.: lignans unchanged

• Microwave:– for 10 min.: minor losses

• Pressure cooker:– for 30 min: losses of polyphenols at ph <6– alpha-tocopherol: not modified

• Lignans: the least affected polyphenols

SQUALENESQUALENE

0

50

100

150

200

250

300

350

400

Extra-verginRefinedSeed oil

SQ

UA

LEN

E M

G/1

00

G

Squalene: potential chemopreventive agent.Smith TJ. (University of South Carolina, USA), 2000

The average intake: 30 mg/day in the United States

200-400 mg/day in Mediterranean countries (olive oil).

Experimental studies have shown that squalene can effectively inhibit chemically-induced colon, lung and skin tumourigenesis in rodents.

The mechanisms involved: •inhibition of Ras farnesylation, •modulation of carcinogen activation•anti-oxidative activities.

Int J Cancer 2000 Aug 1;87(3):444-51Diet, metabolic polymorphisms and dna adducts: the EPIC-Italy cross-sectional study.Palli D, Vineis P, Russo A, et al. (Florence, Italy)

DNA adducts in peripheral leukocytes: reliable indicator of internal dose exposure to genotoxic agents and cancer risk.

EPIC-Italy (section of European prospective study): 47,749 men and women, aged 35-64 years, in 5 centres.

Among 309 volunteers, 72.8% had detectable levels of DNA adducts.

Strong negative associations emerged with the reported frequency of consumption of fresh fruit and vegetables, olive oil, and the intake of antioxidants.

DNA adducts were higher in subjects with GSTT1 null genotype (p = 0.05).

Cancer Preventive role of Cancer Preventive role of

olive oilolive oil Study projectStudy project

CASES CONTROLS Italy 12000 10000

Greece 1500 1500

Spain ? ?

Dieta Mediterranea e prevenzione dei tumori e

delle malattie cardiovascolari

MICRONUTRIENTI & SOSTANZE MICRONUTRIENTI & SOSTANZE BIOATTIVEBIOATTIVE

VIT. C, E, ACIDO FOLICO, SE FRUTTA & VERDURA

LUTEINA VEGETALI GIALLI E VERDI

LICOPENE POMODORO

FLAVONOIDI FRUTTA & VERDURA, THE, VINO

CUMARINE AGRUMI

DITIOLTIONI

CRUCIFEREISOTIOCIANATI

INDOLO-3- CARBINOLO

DIALLIL SOLFIDE

AGLIOALLIL METIL TRISOLFIDE

FLAVONOIDI

* Responsabili dei colori di molti vegetali

* Presenti in semi, agrumi, the, vino rosso

* Azione antiossidante e antiproliferativa

CAROTENOIDI E CANCROCAROTENOIDI E CANCRO• Luteina < incidenza Ca mammella

(premenopausa)

> apoptosi• Zeaxantina < Ca mammella (in storia

familiare positiva!)

Vegetali gialli (arance, carote,

pomodori)Spinaci, broccoli,

sedano

ANTIOSSIDANTI E ANTIOSSIDANTI E FRUTTAFRUTTA

(Unità ORAC)(Unità ORAC)

• Arancia 1 983 unità• Succo di arancia 1 bicchiere 1142 unità• Fragole una tazza 1170 unità• Prugne nere 3 1454 unità• Mirtilli 1 tazza 3480 unità • Melone 3 fette 197 unità • Pesca 1 222 unità• Mela 1 301 unità• Spinaci cotti 1 tazza 2042 unità• Succo di uva nera un bicchiere 5216 unità• More 1 tazza 1466 unità

ANTIOSSIDANANTIOSSIDANTI E FRUTTATI E FRUTTA

(Unità ORAC)(Unità ORAC)

• Arancia 1 983 unità• Succo di arancia 1 bicchiere 1142 unità• Fragole una tazza 1170 unità• Prugne nere 3 1454 unità• Mirtilli 1 tazza 3480 unità • Melone 3 fette 197 unità • Pesca 1 222 unità• Mela 1 301 unità• Spinaci cotti 1 tazza 2042 unità• Succo di uva nera un bicchiere 5216 unità• More 1 tazza 1466 unità

IL TUMORE DELLO IL TUMORE DELLO STOMACO STOMACO

QUANTA FRUTTA E QUANTA FRUTTA E VERDURA ?VERDURA ?

QUANTA FRUTTA E QUANTA FRUTTA E VERDURA ?VERDURA ?

• 500 – 600 g al giorno• Almeno 5 porzioni al giorno• Ogni porzione in più: < 10% rischio di CRC • La più ampia varietà possibile • Stagionalità, locoregionalità

CALORIE ,PESO CALORIE ,PESO e SALUTE (?!?)e SALUTE (?!?)CALORIE ,PESO CALORIE ,PESO e SALUTE (?!?)e SALUTE (?!?)

•

Quintili di Calorie ORs (95% CI)

1 1

2 1.10 (0.92-1.31)

3 1.18 (0.99-1.42)

4 1.16 (0.97-1.39)

5 1.50 (1.25-1.80)

Continuous (100 kcal/day) 1.02 (1.01-1.03)

COLON-RETTO

(Franceschi ,Giacosa et al, 97)

CALORIE & CANCRO DEL COLON

Studio Italiano

ATTIVITA’ FISICA ATTIVITA’ FISICA E CANCRO DEL COLONE CANCRO DEL COLON

ATTIVITA’ FISICA ATTIVITA’ FISICA E CANCRO DEL COLONE CANCRO DEL COLON

0 1 2 3 4 5

Livello di attività fisica

Ris

chio

re

lati

vo

0.6

1

2

Slattery et al, 97

CARBOIDRATI &CARBOIDRATI &

CANCRO DEL COLON CANCRO DEL COLON Studio ItalianoStudio Italiano

CARBOIDRATI &CARBOIDRATI &

CANCRO DEL COLON CANCRO DEL COLON Studio ItalianoStudio Italiano

Alimenti ORs in highest (95% CI)vs lowest quintile

Pane e farinacei 1.69 (1.36-2.10)

Dolci 1.13 (0.93-1.37)

Zucchero 1.43 (1.19-1.73)

Patate 1.20 (0.96-1.51)

COLON-RETTO

(Franceschi ,Giacosa et al, 97)

CHO & CANCRO DELLA CHO & CANCRO DELLA MAMMELLAMAMMELLA

Quintile di consumo

1 (basso) 2 3 4 5 (alto)

Carboidrati disponibili

OR 1 1.05 1.13 1.16 1.29

Amidi

OR 1 1.05 1.28 1.24 1.39

Lancet, 96

IPOTESI INSULINICAIPOTESI INSULINICAIPOTESI INSULINICAIPOTESI INSULINICA

• Le farine raffinate e gli zuccheri possono indurre:

- sovraccarico glicemico

- resistenza insulinica

• Ciò può indurre promozione della crescita cellulare

• Attraverso ormoni specifici e fattori di crescita

RELAZIONE TRA BMI E RISCHIO DI MORTALITA’

RISCHIO DI MORTALITA’

BODY MASS INDEX (kg/m2)

20 25 30 35 40

2.5

2

1.5

1

-------------------------------------------------------------------------

COMPLICANZE DELL’OBESITA’

METABOLICHE

• DIABETE • DISLIPIDEMIA• GOTTA

CARDIOVASCOLARI

• IPERTENSIONE• EVENTI CEREBROVASC.• CORONOPATIA• SCOMPENSO CARDIACO• INSUFFICIENZA VENOSA

ALTRE

• COLELITIASI • CALCOLOSI RENALE • APNEE NOTTURNE • ARTROSI ERNIA IATALE

L’ERNIA IATALEL’ERNIA IATALE

• IL REFLUSSO

• IL DOLORE

• IL BRUCIORE

• MAL DI CUORE ?

• ASMA?

• TOSSE?

Ernia iataleErnia iataleEsofagiteEsofagite

Esofago di BarrettEsofago di Barrett

•

L’ERNIA IATALEL’ERNIA IATALE

Calcolosi della colecistiCalcolosi della colecisti

Calcolosi della colecistiCalcolosi della colecisti

DIETA E PREVENZIONE DIETA E PREVENZIONE DEI TUMORIDEI TUMORI

DIETA E PREVENZIONE DIETA E PREVENZIONE DEI TUMORIDEI TUMORI

Evita il soprappeso e l’obesità e tieni costantemente

sott’occhio il peso corporeo, stando attento a ciò che mangi

ed evitando la sedentarietà.

Mantieni attivo il fisico durante tutta la vita, effettuando almeno

mezz’ora al giorno di attività fisica intensa, ma

adeguando il tipo di esercizio al variare dell’età.

Assumi spesso alimenti ricchi

in fibre e prodotti integrali.

Cerca di assumere almeno

cinque porzioni al giorno tra frutta e

verdura.

Cerca di limitare il

consumo di zucchero,

dolci e prodotti con

farina bianca.

Modera l’apporto di grassi di origine animale (ad esempio latticini e carni grasse) scegliendo

spesso latte e formaggi magri e togliendo il grasso visibile dalla carne e la pelle dal pollo.

Per la cottura e per i condimenti, scegli preferibilmente olio extra-vergine d’oliva.

Ricordati che il pesce e i legumi sono

splendide alternative alla carne.

Inoltre, l’olio presente nel pesce è utile per prevenire vari tumori (soprattutto il

tumore della mammella) e le malattie cardiovascolari.

Bevi acqua in abbondanza

e, se assumi alcolici, bevial massimo due bicchieri al giorno di vino o birra se sei di sesso maschile,

uno se sei di sesso femminile.

La scelta e lo stoccaggio degli alimenti sono molto importanti. Controlla sempre l’etichetta e, per i vegetali, cerca di preferire

prodotti locali, stagionali e freschi o surgelati.

Per cucinare in modo salutare, fai uso di piccole quantità di

grasso e olio, utilizza basse temperature e

riduci il più possibile i tempi di cottura.

This study provides evidence that an a

priori defined nutritional pattern,

which includes several aspects of the

Mediterranean diet, favourably affects the risk of cancers of the upper aerodigestive

tract

Mediterranean diet score and cancers of the upper digestive tract