This document discusses the relationship between diet and gastrointestinal cancers. It finds that habitual consumption of processed meats is clearly associated with increased risk of colon and pancreatic cancers. A diet high in red meats cooked at high temperatures also increases risk of stomach and intestinal cancers. Obesity is causally linked to gastrointestinal cancers through mechanisms like alterations in insulin signaling, inflammation from adipose tissue, and changes in sex hormone levels and metabolism. A pro-inflammatory diet pattern, as measured by the dietary inflammatory index score, is associated with increased risk of colorectal cancers.

1. I TUMORI DELL'APPARATO DIGERENTE:
DALLA PREVENZIONE ALLA CURA
ROMA
HOT TOPICS IN
GASTROENTEROLOGIA
Cosa è cambiato e cosa bisogna sapere
DIETA E TUMORI DELL'APPARATO DIGERENTE
Riccardo Marmo

2. Cause di Morte (ICD) Stili di vita
Alimenti
Biologici
e
genetici
Ambientali Assistenza
Sanitaria
1 – Tumori
2 – Cardiopatia ischemica
3 – Cerebrovasculopatie
acute
4 – Altre forme di cardiopatia
5 – Bronchite, enfisema,
asma
6 – Polmonite
7 – Tutti gli incidenti
8 – Incidenti automobilistici
9 – Diabete mellito
10 - Suicidi
40
50
40
32,5
35
25
52,5
60
30
50
30
20
25
32,5
25
15
5
5
50
15
20
10
20
17,5
30
35
35
20
5
20
10
10
5
7,5
10
20
10
5
10
5
Determinanti dello stato di salute e riduzione delle 10 principali cause di morte

3. L’uso abituale di Carni trasformate si è chiaramente dimostrato
associato allo sviluppo di tumori del colon, del pancreas
Una dieta ricca in carni cotte ad alte temperature, alla griglia, alla
brace aumenta il rischio di tumori dello stomaco e dell’intestino
Alimentazione

4. Sistema complesso
insieme di elementi variabili e fortemente interconnessi anche nella loro evoluzione temporale, sicché la conoscenza singola
d’ognuno di essi non è sufficiente a stabilire l’evoluzione complessiva del sistema.
è composto da un numero notevole di sottosistemi interagenti; presenta caratteristiche emergenti, cioè comportamenti
ordinati derivanti dalle interazioni fra i sottosistemi quando i sottosistemi stessi o le loro connessioni superano un certo
numero; è altamente strutturato;
presenta meccanismi di retroazione (per cui una risposta in uscita diventa anche uno stimolo in entrata); è caratterizzato da
una dinamica non lineare e sensibile alle condizioni iniziali (→ caos) teoria delle catastrofi,

5. Stabilità strutturale
Interdipendenza e controllo reciproco

6. Sistema complesso : sistema coordinato e interdipendente

7. Stabilità strutturale
Insulti e perturbazioni costanti e continue
Inapparenti
Interdipendenza e controllo reciproco

8. Adiposity and gastrointestinal cancers:
epidemiology, mechanisms and future directions
A large body of epidemiological evidence supports a causal
relationship between excess adiposity and gastrointestinal cancers.
• With the rising prevalence of obesity worldwide, this relationship could
represent a growing source of cancers of the gastrointestinal system.
•
Neil Murphy, Mazda Jenab and Marc J. Gunter Nature Reviews | Gastroenterology & Hepatology sept 2018

9. Obesity
Overweight
Underweigh
t

10. Adiposity and gastrointestinal cancers:
epidemiology, mechanisms and future directions
A large body of epidemiological evidence supports a causal relationship
between excess adiposity and elevated risk of developing
gastrointestinal cancers.
• With the rising prevalence of obesity worldwide, this relationship could
represent a growing source of cancers of the gastrointestinal system.
• Experimental and molecular epidemiological studies indicate important roles
for alterations in insulin signalling, adipose tissue derived inflammation
and sex hormone pathways in mediating the association between
adiposity and gastrointestinal cancer
Neil Murphy, Mazda Jenab and Marc J. Gunter Nature Reviews | Gastroenterology & Hepatology sept 2018

11. Risk estimates for overall and abdominal adiposity and
individual gastrointestinal cancers
Type ofcancer rr with BMIper5kg/m2
(95% CI) rr with waist circumference(95% CI) rr with waist-to-hip ratio(95% CI)
Colon(men) RR1.10 (1.07–1.13)1 RRper 10 cm 1.07 (1.02–1.12)1 RRper 0.1 unit 1.36 (1.05–1.74)1
Colon(women) RR1.04 (1.02–1.06)1
RRper 10 cm 1.03 (1.01–1.04)1
RRper 0.1 unit 1.16 (1.00–1.34)1
Rectal (men) RR1.02 (1.01–1.04)1 RRper 10 cm 1.01 (0.98–1.03)1 RRfor highest versus lowest category
1.33(0.94–1.71)1a
Rectal (women) RR1.01 (0.99–1.03)1 RRper 10 cm 1.03 (1.01–1.06)1 RRfor highest versus lowest category
1.19(0.88–1.50)1a
Smallintestine
(men andwomen)
RRfor ≥35 kg/m2 versus <25kg/m2
1.77(1.11–2.82)27 RRper 5cm 1.18 (0.98–1.42)28 RRper percentage increase 1.02
(0.99–1.06)28
Pancreatic(men) RR 1.13(1.04–1.22)29 RRper 10 cm 1.13 (0.89–1.44)4 Men and women combined RR per
0.1 unit 1.19 (1.09–1.31)4
Pancreatic(women) RR 1.10(1.04–1.16)29
RRper 10 cm 1.14 (1.02–1.28)4
Liver(men) RR1.21 (1.02–1.44)2
RRper 5cm 1.07 (1.01–1.13)36 Men and women combined RR
per 0.1 unit 1.45 (1.16–1.83) (ref.37)b
Liver (women) RR1.21 (1.10–1.33)2
RRper 5cm 1.11 (1.04–1.18)36
Gallbladder (men) RR1.23 (1.13-1.33)7 RRper 5cm 1.12 (1.02–1.24)41 RRper 0.1 unit 1.22 (0.89–1.66)41
Gallbladder (women) RR1.25 (1.07–1.45)7
RRper 5cm 1.09 (1.03–1.14)41
RRper 0.1 unit 1.09 (0.92–1.30)41
Stomach cardia
(men andwomen)
RR1.23 (1.07–1.40)5 RRfor highest versus lowest category
1.87 (1.19–2.54) (refs43,141
)c
RRfor highest versus lowest category
1.50 (0.98–2.02) (refs43,141
)c
Stomach non-cardia
(men and women)
RR0.93 (0.85–1.02)5 RRfor highest versus lowest category
1.25 (0.75–1.75) (refs43,141
)c
RRfor highest versus lowest category
1.71 (1.00–2.42) (refs43,141
)c
EAC(men) RR1.56 (1.39–1.74)3 Men and women combined RR1.34
(1.17–1.52)3
Men and women combined RR per
0.1 unit 1.38 (1.10–1.73)3
EAC(women) RR1.48 (1.29–1.71)3
EAC, oesophageal adenocarcinoma; ESCC, oesophageal squamous cell carcinoma
Nature reviews | G ast ro en t ero loG y & HepatoloGy

13. O b e s i t y a n d g a s t r O i n t e s t i n a l c a n c e r
Targe
tcel
l
Recepto
r
I
R
IGFI
R
Gastrointestinal tract tumourdevelopment
i Angiogenesis
i Proliferation and/or
survival
-!Apoptosis
TNF
i CRP IL-
1�
IL-6
Bioavailab
le
oestrogen
s
iLeptin
-!
Adiponectin
-!
SHBG
i
Insulin
Obesity
E
R
Recepto
r
Fig. 3 | Major established mechanismslinking adiposity and gastrointestinal
cancers.Adiposity is associated with substantial metabolic and endocrine
abnormalities. Three leading hypotheses have emerged to explain the link between
adiposity and cancer: alterations in insulin signalling, dysregulation of adipose tissue-
derived inflammation and hormonal pathways and sex hormone metabolism. CRP,C-
reactive protein; ER,oestrogen receptor; IGFIR,insulin-like growth factor I receptor
(also known
as IGF1R); IR,insulin receptor; SHBG, sex hormone-binding globulin.
Nature reviews | Gastro e n t er o l o G y & HepatoloGy

14. Nutrients 2017, 9, 1043; doi:10.3390/nu9091043
Review
Dietary Inflammatory Index and Colorectal Cancer Risk—A Meta-Analysis
Nitin Shivappa Justyna Godos , James R. Hébert , Michael D. Wirth , Gabriele Piuri , Attilio F.Speciani and Giuseppe Grosso

15. Association Between Inflammatory Diet Pattern and Risk of Colorectal
Carcinoma Subtypes Classified by Immune Responses to Tumor
Li Liu,1,2,3,
* Reiko Nishihara,1,2,4,5,6,
* Zhi Rong Qian,1,
* Fred K. Tabung,2,4,
* Daniel Nevo,4,5
Xuehong Zhang,7
Mingyang Song,2,8,9
Yin Cao,2,8,9
Kosuke Mima,1
Yohei
Masugi,1
Yan Shi,1,10
Annacarolina da Silva,1
Tyler Twombly,1
Mancang Gu,1,11
Wanwan Li,1
Tsuyoshi Hamada,1
Keisuke Kosumi,1
Kentaro Inamura,12
Jonathan A.
Nowak,6
David A. Drew,8,9
Paul Lochhead,8,9
Katsuhiko Nosho,13
Kana Wu,2
Molin Wang,4,5,7
Wendy S. Garrett,14,15
Andrew T. Chan,7,8,9,§
Charles S. Fuchs,16,17,18,§
Edward L. Giovannucci,2,4,7,§
and Shuji Ogino1,4,6,19,§
Gastroenterology 2017;153:1517–1530
Methods
Study Population
The study was based on participants in 2 ongoing prospective cohort studies, the NHS and the HPFS.
The NHS recruited 121,701 registered female nurses aged 30-55 years at baseline in 1976, and the HPFS
enrolled 51,529 male health professionals aged from 40 to 75 years at baseline in 1986 in the United States.
In both cohorts, questionnaires were sent at baseline and every 2 years thereafter to collect and update demographic, lifestyle, medical, and other health-related
information.
Validated food frequency questionnaires were administrated in 1980, 1984, and 1986, and every 4 years thereafter in the NHS, and in 1986 and every 4 years
thereafter in the HPFS to collect dietary data.
We followed participants from the date of return of the baseline questionnaire through June 30, 2012 in the NHS or January 31, 2012 in the HPFS. We obtained
written informed consent from all participants. This study was approved by Human Subjects Committees at Harvard T.H. Chan School of Public Health and Brigham and
Women’sHospital.

16. Association Between Inflammatory Diet Pattern and Risk of Colorectal
Carcinoma Subtypes Classified by Immune Responses to Tumor
Li Liu,1,2,3,
* Reiko Nishihara,1,2,4,5,6,
* Zhi Rong Qian,1,
* Fred K. Tabung,2,4,
* Daniel Nevo,4,5
Xuehong Zhang,7
Mingyang Song,2,8,9
Yin Cao,2,8,9
Kosuke Mima,1
Yohei
Masugi,1
Yan Shi,1,10
Annacarolina da Silva,1
Tyler Twombly,1
Mancang Gu,1,11
Wanwan Li,1
Tsuyoshi Hamada,1
Keisuke Kosumi,1
Kentaro Inamura,12
Jonathan A.
Nowak,6
David A. Drew,8,9
Paul Lochhead,8,9
Katsuhiko Nosho,13
Kana Wu,2
Molin Wang,4,5,7
Wendy S. Garrett,14,15
Andrew T. Chan,7,8,9,§
Charles S. Fuchs,16,17,18,§
Edward L. Giovannucci,2,4,7,§
and Shuji Ogino1,4,6,19,§
Gastroenterology 2017;153:1517–1530
to identify a dietary pattern most predictive of 3 plasma inflammatory
biomarkers, IL6, C-reactive protein, and TNFRSF1B (TNFa receptor 2).
The EDIP score is the weighted sum of 18 food groups, with
higher (more positive) scores indicating pro- inflammatory diets
and lower (more negative) scores indicating anti-inflammatory diets

17. Association Between Inflammatory Diet Pattern and Risk of Colorectal
Carcinoma Subtypes Classified by Immune Responses to Tumor
Li Liu,1,2,3,
* Reiko Nishihara,1,2,4,5,6,
* Zhi Rong Qian,1,
* Fred K. Tabung,2,4,
* Daniel Nevo,4,5
Xuehong Zhang,7
Mingyang Song,2,8,9
Yin Cao,2,8,9
Kosuke Mima,1
Yohei
Masugi,1
Yan Shi,1,10
Annacarolina da Silva,1
Tyler Twombly,1
Mancang Gu,1,11
Wanwan Li,1
Tsuyoshi Hamada,1
Keisuke Kosumi,1
Kentaro Inamura,12
Jonathan A.
Nowak,6
David A. Drew,8,9
Paul Lochhead,8,9
Katsuhiko Nosho,13
Kana Wu,2
Molin Wang,4,5,7
Wendy S. Garrett,14,15
Andrew T. Chan,7,8,9,§
Charles S. Fuchs,16,17,18,§
Edward L. Giovannucci,2,4,7,§
and Shuji Ogino1,4,6,19,§
Gastroenterology 2017;153:1517–1530
EDIP score = (165.03443 x processed meat) + (140.19344 red meat) + (144.60554 organ
meat) + (252.44533 x other fish) + (136.14430 x other vegetables) + (81.21217 refined grain)
+ (156.84543 x high energy beverage)+ (94.77015 x low energy beverage) + (167.91804 x
tomato) - (136.99127 x beer) - (249.70411 x wine) - (42.25228 x tea) - (83.17692 x coffee) -
(165.37317 x dark yellow vegetable)- (190.28539 x green leafy vegetable) - (45.08391 x snack)
- (58.94952 x fruit juice) - (1175.21060 x pizza).

18. Pro - inflammatory diets :
high in meat, refined grains, carbonated beverages

19. Anti - inflammatory diets :
low in beer, wine, coffee, tea, yellow and leafy vegetables, and
fruit juice

20. Association Between Inflammatory Diet Pattern and Risk of Colorectal
Carcinoma Subtypes Classified by Immune Responses to Tumor
Li Liu,1,2,3,
* Reiko Nishihara,1,2,4,5,6,
* Zhi Rong Qian,1,
* Fred K. Tabung,2,4,
* Daniel Nevo,4,5
Xuehong Zhang,7
Mingyang Song,2,8,9
Yin Cao,2,8,9
Kosuke Mima,1
Yohei
Masugi,1
Yan Shi,1,10
Annacarolina da Silva,1
Tyler Twombly,1
Mancang Gu,1,11
Wanwan Li,1
Tsuyoshi Hamada,1
Keisuke Kosumi,1
Kentaro Inamura,12
Jonathan A.
Nowak,6
David A. Drew,8,9
Paul Lochhead,8,9
Katsuhiko Nosho,13
Kana Wu,2
Molin Wang,4,5,7
Wendy S. Garrett,14,15
Andrew T. Chan,7,8,9,§
Charles S. Fuchs,16,17,18,§
Edward L. Giovannucci,2,4,7,§
and Shuji Ogino1,4,6,19,§
Gastroenterology 2017;153:1517–1530
However, the association varied with degree of peritumoral lymphocytic reaction (P for heterogeneity < .001).
Compared with the lowest quintile of empirical dietary inflammatory pattern score,
the highest quintile was associated with an absent or low peritumoral
lymphocyte reaction of 2.60 (95% confidence interval, 1.60-4.23; P for trend < .001).
In contrast, there was no association of dietary inflammatory pattern score with cancer with intermediate or high peritumoral lymphocytic reaction (P for trend > 0.80).

21. Association Between Inflammatory Diet Pattern and Risk of Colorectal
Carcinoma Subtypes Classified by Immune Responses to Tumor
Li Liu,1,2,3,
* Reiko Nishihara,1,2,4,5,6,
* Zhi Rong Qian,1,
* Fred K. Tabung,2,4,
* Daniel Nevo,4,5
Xuehong Zhang,7
Mingyang Song,2,8,9
Yin Cao,2,8,9
Kosuke Mima,1
Yohei
Masugi,1
Yan Shi,1,10
Annacarolina da Silva,1
Tyler Twombly,1
Mancang Gu,1,11
Wanwan Li,1
Tsuyoshi Hamada,1
Keisuke Kosumi,1
Kentaro Inamura,12
Jonathan A.
Nowak,6
David A. Drew,8,9
Paul Lochhead,8,9
Katsuhiko Nosho,13
Kana Wu,2
Molin Wang,4,5,7
Wendy S. Garrett,14,15
Andrew T. Chan,7,8,9,§
Charles S. Fuchs,16,17,18,§
Edward L. Giovannucci,2,4,7,§
and Shuji Ogino1,4,6,19,§
Gastroenterology 2017;153:1517–1530
The findings suggest diet-related inflammation might suppress
the adaptive antitumor immune response, thereby contributing to
the development of colorectal cancer.
The study provides population-based evidence for
the potential that dietary interventions could be used a
means of personalized immunoprevention
.

22. Association Between Inflammatory Diet Pattern and Risk of Colorectal
Carcinoma Subtypes Classified by Immune Responses to Tumor
Li Liu,1,2,3,
* Reiko Nishihara,1,2,4,5,6,
* Zhi Rong Qian,1,
* Fred K. Tabung,2,4,
* Daniel Nevo,4,5
Xuehong Zhang,7
Mingyang Song,2,8,9
Yin Cao,2,8,9
Kosuke Mima,1
Yohei
Masugi,1
Yan Shi,1,10
Annacarolina da Silva,1
Tyler Twombly,1
Mancang Gu,1,11
Wanwan Li,1
Tsuyoshi Hamada,1
Keisuke Kosumi,1
Kentaro Inamura,12
Jonathan A.
Nowak,6
David A. Drew,8,9
Paul Lochhead,8,9
Katsuhiko Nosho,13
Kana Wu,2
Molin Wang,4,5,7
Wendy S. Garrett,14,15
Andrew T. Chan,7,8,9,§
Charles S. Fuchs,16,17,18,§
Edward L. Giovannucci,2,4,7,§
and Shuji Ogino1,4,6,19,§
Gastroenterology 2017;153:1517–1530
.

23. Anti-inflammatory Diets
MEASURING CELLULAR INFLAMMATION
Perhaps the best upstream marker of cellular inflammation is the ratio of 2 fatty acids in the blood,
the omega-6 fatty acid arachidonic acid (AA) and the omega-3 fatty acids eicosapentaenoic acid (EPA).
AA is the building block of pro-inflammatory eicosanoids that stimulate inflammation.
EPA is not only a competitive inhibitor of AA for the enzymes necessary for the production of inflammatory eicosanoids but also
the building block for very powerful proresolution mediators such as resolvin E1 and resolvin E2 (RvE2).
Thus, the AA:EPA ratio in the blood provides detailed insight into the balance of inflammation and resolution in every cell in
the body
silent inflammation can elevate the diet from simply a source of
calories
to being on the cutting edge of gene-silencing technology.
Barry Sears (2015) Anti-inflammatory Diets, Journal of the American College of Nutrition, 34:sup1, 14-21,

24. Optimal Ranges for an Anti-inflammatory Diet
Clinical Marker Optimal Range
Arachidonic acid (AA) / Eicosapentaenoic acid (EPA) 1.5-3
TG/HDL ratio <1 (mg/dl)
HbA1c 5%

25. Optimal Ranges for an Anti-inflammatory Diet
Level of calories required for an anti-inflammatory diet to be successful.
Excess calories stimulate the hypothalamus, leading to increased appetite
At every meal, the plate should be divided into 3 equal sections.
1 g of fat (primarily unsaturated fats)
2 g of low-fat protein and
3 g of low-glycemic - load carbohydrates

27. Conclusioni

29. Sistema Complesso
Insulti e perturbazioni costanti e continue
Inapparenti
Infiammazione cronica

30. Sistema Complesso
Insulti e perturbazioni costanti e continue
Inapparenti
Intervenire oggi nel bambino
Prevenire le malattie dell’adulto
Smontare il mito dei “genitori” CIBO E/È AMORE