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Fibra y cancer colorectal
I Jornada Universitaria UCM-CLAS
            Mayo 2012
     H.G.U.Gregorio Marañón.
        Cátedra UCM- CLAS



     Dra. Pilar Riobó Serván
    Endocrinologia y Nutrición
     www.doctorariobo.com
Denis Parsons Burkitt (1911-1993)




Burkitt DP. Epidemiology of cancer of the colon
   and rectum. Cancer. 1971 Jul;28(1):3-13.
Burkitt's observation was followed by
   numerous case-control studies.

• A combined analysis of 13 case-control studies
  as well as a meta-analysis of 16 case-control
  studies indicated an inverse association
  between fiber intake and colorectal cancer.

• 10 prospective studies, which avoid the
  potential for recall and control selection bias,
  have largely failed to support this association.
Associations between consumption of dietary
     fibre and risk of CRC: Studies are level II evidence.
Terry et al,2001   Prospective cohort study of 61   Very low consumption of fruit and
                   463 women                        vegetables raises risk of CRC

Asano and          Meta-analysis (5 randomized      Increase in dietary fibre intake does not
McLeod, 2002       controlled trials)               reduce incidence or recurrence of
                                                    adenomatous polyps

Levi et al, 2001   Case-control study: 286 cases    Vegetable fibre appears to be more
                   vs. 550 controls                 protective against CRC than either fruit or
                                                    grain fibre

Bingham et al,     Prospective cohort study of 19   Intake of fibre was inversely related to
2003               978 patients                     incidence of large-bowel cancer

Mai et al, 2003    Prospective cohort study         No association between fibre intake and
                                                    CRC

Peters et al,21    Cancer screening trial           High dietary fibre lowers risk of adenomas
2003
Meat???
• countries that consume a lot of meat and
  animal fat have the highest rates of CCR
• this inversely correlates with the consumption
  of dietary fiber
• The protection that fibre offers could be
  dependent on the type of fibre
  – cereals type fibre
  – Vegetable fibre
  – Fruit fiber
Colorectal cancer incidence lower in Africa
Incidence rates :
      USA: 35.8 cases/ 100,000/year
      UK: 12/100,000/y (40-44 y); 24/100,000/y (45–49y)
      Nigeria: 3.4/100,000/year, but increasing incidence:
      (by the last decade, carcinoma of the colon and
      rectum moved from the tenth to the fourth position)
      Relative absence of premalignant conditions like
      adenomatous polyps in West African
Body Mass Index Increases Risk for
Colorectal Adenomas (Meta-analysis)
36 independent studies, 29,860 incident cases of CRA.
A 5-unit increase in BMI, increased the risk for CRA
  (relative risk = 1.19)
increased risk of CRA in obese was independent of
  race, sex, adenoma progression, and confounders.
The association between increased BMI and risk for
  CRA was stronger for colon than rectal adenoma.
A 5-unit increase in BMI was associated with a 19%
  increased risk for colorectal adenoma

                                Ben Q. Gastroenterology. 2012 Apr;142(4):762-72.
•   34,467 women, who had undergone colonoscopy
•   Fruits and vegetables intake was assessed/2 years, FFQ
•   1,720 cases of adenoma were diagnosed (1980 – 1998).
•   Fruit consumption was inversely related to the risk of polyps,
    but little association was found for vegetable consumption.
     – five or more servings of fruit a day had OR: 0.60 for
       developing colorectal adenomas (P = 0.001).
     – OR for vegetable consumption was 0.82 (P = 0.1).
     – four or more servings of legumes per week had a lower
       incidence of colorectal adenomas (OR, 0.67. P = 0.005).
•   2818 persons who had undergone colonoscopy.
•   Self-administered questionnaire from AHS-1, 1976
•   outcome was assessed from AHS-2 data (2002 - 2005)
•   Results:
    – A total of 441 cases of colon polyps were identified.
    – total fiber intake was inversely associated with the risk of
      colon polyps (OR for highest vs lowest quartile 0.71, 95% CI
      0.51–0.99).
    – Vegetables &legumes (OR for highest vs lowest quartile
      0.65; p .02).
    – This association showed a dose-response effect (p .04).
Fibra y cancer colorectal
Total dietary fiber intake, specifically from vegetables, was inversely
associated with colon polyps, with a clear dose-response effect.
 Fiber intake from fruits and grains did not show a significant effect
on colon polyps
• Prospective cohort: 59000 African American women
• 155,414 person-years of follow-up (1997 to 2007)
  women who had had at least one colonoscopy
• Two dietary patterns, Western and prudent, were
  utilized
  – 620 incident cases of colorectal adenomas were identified.




                Cancer Epidemiol Biomarkers Prev; 20(5); 818–25
The highest quintile of prudent diet, relative to the
lowest quintile, was significantly associated with 34% lower
colorectal adenoma risk (IRR = 0.66; P< 0.01).
       Higher scores on the Western pattern were associated
   with a higher risk of developing colorectal adenoma (IRR
   = 1.42; 95% CI, 1.09–1.85 for the highest quintile relative
   to the lowest; P = 0.01).
Tennessee Colorectal Polyp Study.
                                                Participants (40–75 y)
                                                   colonoscopy from
                                                   2003 to 2005.
                                                Dietary intake was
                                                   assessed

                                                764 cases and
                                                1517 controls

increased intakes of total fruits, berries, fruit juice, and green leafy
vegetables were associated with reduced adenoma risk
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (1993–2001)


                                               3057 cases with 1 adenoma
                                                 29 413 control subjects.

                                                 FFQ to quantify intake of
                                                fruit and vegetables in the
                                                  12 mo before screening



Diets rich in fruit and deep-yellow vegetables, dark-green
vegetables, and onions and garlic are modestly associated
         with reduced risk of colorectal adenoma
dietary fiber intake was inversely associated
with risk of colorectal cancer in age-adjusted analyses.
However, after accounting for other dietary risk factors,
  high dietary fiber intake was not associated with a
           reduced risk of colorectal cancer.
•   Prospectively assess the association between the Alternate Mediterranean Diet
    (aMed) and the DASH-style diet scores and risk of colorectal cancer

•  A total of 87,256 women and 45,490 men , followed for 26 y.
•  The aMed and DASH scores were calculated for each participant by using dietary
   information that was assessed ≤7 times during follow-up.
Results:
• 1432 cases of incident colorectal cancer among women and 1032 cases in men.
• Comparing top with bottom quintiles of the DASH score, the pooled RR for total
   colorectal cancer was 0.80 (P for trend = 0.0001).
• No association was observed with aMed score.



• Conclusion: Adherence to the DASH diet (higher intakes of whole grains,
  fruit, and vegetables; moderate amounts of low-fat dairy; and lower
  amounts of red or processed meats, desserts, and sweetened beverages)
  was associated with a lower risk of colorectal cancer.
1.8 million person-years and 1,596 cases of CRC
       little association with fiber intake
European Prospective into Cancer (EPIC)
•   519 978 individuals; FFQ in 1992—98
•   Follow-up consisted of 1 939 011 person-years,
•   1065 reported cases of colorectal cancer
•   Dietary fibre in foods was inversely related to incidence of CRC
•   RR for the highest versus lowest quintile of fibre intake was 0·58
•   No food source of fibre was more protective than others
•   Critics:
    – included various populations, ranging from Scandinavia to the
      Mediterranean, with diverse dietary habits.
    – Folate intake was not controlled

        In populations with low average intake of fibre, an
       approximate doubling of total fibre intake from foods
         could reduce the risk of colorectal cancer by 40%.
• 45 491 women in the Breast Cancer Detection
  Demonstration Project (BCDDP) follow-up cohort.
• A 62-item FFQ was administered in 1987-89 and
  follow-up questionnaires (in 1992–95 and 1995–98)
• follow-up time of 8.5 years,
• 487 CRC cases
• No evidence that dietary fibre intake lowers CRC risk
• Critics: cohort of older women characterized by a
  relatively low fibre intake
Fibra y cancer colorectal
Fibra de frutas




           Aune D et al BMJ 2011;343:d6617
Fibra de vegetales




            Aune D et al BMJ 2011;343:d6617
Fibra de legumbres




            Aune D et al BMJ 2011;343:d6617
Fibra de cereales




            Aune D et al BMJ 2011;343:d6617
Grano integral




           Aune D et al BMJ 2011;343:d6617
The relative risk of colorectal cancer for
              each 10 g/day intake was:
                  0.90 for total fibre
                   0.93 for fruit fibre
               0.98 for vegetable fibre
                 0.62 for legume fibre
                  0.90 for cereal fibre

In addition to a high total dietary fibre , cereal fibre
    and whole grains may reduce the risk of CRC
 The relative risk for an increment of three servings
            daily of whole grains was 0.83
Mechanisms for a reduced risk of
  colorectal cancer with high fiber intake
• high stool bulk, dilution, absorption, and removal of
  carcinogens, cocarcinogens, and/or tumor promoters
• reduces stool transit time ->lowers exposure to potential
  carcinogens.
• bind to bile acids potentially lessening their toxic effects.
• Cereal fibre and whole grains are rich in inositol
  hexaphosphate (IP6) that has been proven to reduce
  experimental cancers, not just of the CRC but of other organs
• fibre is fermented to volatile fatty acids ,
   – protective in experimental models of carcinogenesis.
   – lowers the pH, which prevents the conversion of primary to secondary
     bile acids
Efectos del butirato sobre el colon




 •   inhibition of inflammation and carcinogenesis,
 •   reinforcing various components of the colonic defence barrier
 •   decreasing oxidative stress.
 •   may promote satiety.
 •   inhibition of nuclear factor kappa B activation
 •   histone deacetylation.
Hamer HM. the role of butyrate on colonic function.Aliment Pharmacol Ther. 2008 15;27(2):104-19
elevated luminal butyrate
                                                 as delivered by HAMSB
                                                  increased the rate of
                                              apoptosis but not colonocyte
                                                proliferation in the distal
                                                  colon of rats in acute
                                               response toAOM-induced
                                                       genotoxicity



• Proapoptotic function of butyrate plays a major role
  reducing tumour formation in the AOM-treated rat
                  Carcinogenesis. 2012 January; 33(1): 197–202.
Otros factores carcinogenos/
      anticarcinogenos
Spices and Phytonutrients
• Turmeric (curcumin, curry) has anticancer properties
   – it targets multiple signalling pathways that may protect the
     colon by decreasing the activity of beta-glucuronidase and
     mucinase
   – Other anticancer properties :
       • inhibition of lipooxygenase activity, specific inhibition of
         cyclooxygenase 2 expression, and the promotion/progression
         stages of carcinogenesis [55, 56].
• Garlic and onions, contain diallyl sulphide and flavonoids
   – suppress cell division in human colon tumor cells
   – high antioxidant property (due to their wide content of) ;


• Red pepper (chili ) has been shown to protect against
  colorectal carcinoma
   – The main ingredient of pepper is capsaicin, and this is known to cause death
     of colon cancer cells.
Dietary constituent which may decrease
    tumor risk in colon and rectum




                           Correa Lima , Nutr Hosp 2005
• The EPIC study is a prospective cohort to investigate
  the associations between dietary, lifestyle, genetic, and
  environmental factors and risk of specific cancers.

• 366,521 women and 153,457 men enrolled between
  1992 and 1998 in 10 European countries


  There is convincing evidence that physical
    activity reduces colon cancer risk
Actividad fisica y cancer de colon
Kaiser Permanente Medical Care Program (1997 - 2002)




Vigorous physical activity was associated with reduced risk of
rectal cancer (OR = 0.60) Participation in vigorous activity over the
past 20 years conferred the greatest protection (OR = 0.55, 95% CI:
0.39, 0.78 for men; OR = 0.44, 95% CI: 0.30, 0.67 for women).
•Lifestyle index: physical activity, waist, smoking, alcohol, and
diet (fibre, fat, red and processed meat, fruits and vegetables)
•Follow-up: 9.9 years, 678 persons had CRC diagnosed.

• 13% (95% CI 4% to 22%) of CRC were attributable to lack of
adherence to one additional recommendation
•If all participants had followed the 5 recommendations, 23% (9%
to 37%) of CRC might have been prevented.
•   37,112 persons from Australia, recruited from 1990 to 1994
•   9 years of follow-up
•   Diet was measured with a FFQ
•   283 colon cancers and 169 rectal cancers

Consumption of fresh red meat and processed meat seemed to
  be associated with an increased risk of rectal cancer.
Consumption of chicken and fish did not increase risk.
    Dietary heme injures surface epithelium, hyperproliferation,
      inhibition of apoptosis and crypt hyperplasia in rat colon
                       Cancer Epidemiol Biomarkers Prev 2004;13(9):1509–14)
Daily increase of 100 g of
 all meat or red meat is
    associated with a
   significant 12–17%
  increased risk of CRC


    A significant 49%
   increased risk was
    found for a daily
   increase of 25 g of
    processed meat
Heterocyclic amines (HCAs)
• Meat cooked at high temperatures contains HCA

• Produced when meat is heated above 180°C for long periods, and
  these HCAs have consistently been identified in well-done meat

•    Meat grilled or barbecued contains the highest amount of
    polycyclic aromatic hydrocarbons (PAHs) because of the exposure to
    smoke formed from the pyrolysis of fatty juices that drip down onto
    the heat source

• The poor electricity supply in most rural and urban areas in Africa
  does not allow proper refrigeration of meat, thus many households
  deep-fry meat for preservation and consumption.
Netherlands Cohort Study on diet and cancer
 2,323 CRC cases, after 13.3 years of follow-up.
 • Compared to abstaining, alcohol consumption of
   ≥30.0 g/day (∼3 alcoholic drinks) was positively
   associated with the risk of CRC (HR: 1.32,).
 • Cancer risk seemed to increase from proximal
   colon through rectum;
    – HR: 1.29, for proximal colon cancer,
    – HR: 1.41, for distal colon cancer,
    – HR: 2.07, for rectosigmoid cancer
• CRC risk for beer (HR 1.38) was higher than wine (HR 5 1.21)
• Higher HRs for baseline alcohol with low levels of folate intake
Folate and CRC risk
• epidemiologic studies have found an inverse relationship between
  high intake of folate & CRC risk, but not consistentely
• Reduction of 30%-40% in CRC risk for persons with high levels of
  folate intake compared to those with low levels
• The risk of CRC decreases 11% for every 400 μg of folate ingested.
• BUT…
• Animal studies have suggested that high-dose folic acid might
  promote colorectal tumorigenesis
• A large, placebo-controlled multicenter trial has shown that high-
  dose folate might increase the risk of neoplastic transformation
• A multicenter, randomized, double-blind trial has shown that folate
  supplementation was found to have no effect on adenoma
  recurrence [relative risk (RR) = 1.07, 95% CI: 0.85-1.34
Folate and CRC risk




dietary folate supplementation protection against
 colonic carcinogenesis might depend on the stage
   of colorectal carcinogenesis, and would protect
 against carcinogenesis in normal colorectal tissue,
 but that folate might enhance pre-existing lesions
Vitamina D
Actividad anticancer de la vit D?
       en animales y en líneas celulares durante años.

1,25(OH)2D estimula la expresión de inhibidores del
ciclo celular p21 y p27 y de E-cadherina e inhibe la
actividad de β-catenina

1,25(OH)2D repara el DNA dañado por UVR

Hay evidencias epidemiológicas que apoyan el papel
de la vitamina D para la prevención de ciertos canceres,
sobre todo mama, colon y prostata.
Premature mortality due to cancer in white females, and
males as determined on the basis of the July 1992 DNA-
weighted ultraviolet B (UV-B) radiation by use of a total
ozone mapping spectrometer




                              Holick, M. F Am J Clin Nutr 2004;79:362-371
Multivariable relative risks for an increment of 25
nmol/L in predicted plasma 25-hydroxy-vitamin D
level for individual cancers in the Health
Professionals Follow-up Study (1986-2000)




                                                   Low levels of vitamin D may be
                                                     associated with increased
                                                   cancer incidence and mortality
                                                      in men, particularly for
                                                     digestive-system cancers.



      Giovannucci, E. et al. J. Natl. Cancer Inst. 2006 98:451-459; doi:10.1093/jnci/djj101
Los individuos con ingesta ≥1000 IU/día de Vitamina D o
     con niveles séricos ≥33 ng/ml (82 nmol/l) de 25-
hydroxyvitamin D tenían una incidencia 50% más bajas de
                 cancer colorectal cancer

Son necesarias acciones para aumentar la ingesta de D3 a
                      1000 IU/día



Gorham ED. Vitamin D and prevention of colorectal cancer. J Steroid
Biochem Mol Biol 2005;97:179-194.
Professionals Health
       Study
179 casos de cancer
 Acociacion inversa
 entre vitamina D y
 Cancer colorectal
74.000 japoneses
                                                No asociacion con
                                                   vitamina D
                                                Pero si con calcio




. Ishihara, M. Inoue, M. Iwasaki, S. Sasazuki, and S. Tsugane
Dietary calcium, vitamin D, and the risk of colorectal cancer
Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1576 - 1583.
Interrelationship among risk factors for colon cancer




        Davis, C. D. et al. J. Natl. Cancer Inst. 2007 99:1563-1565;
Cancer



           PCRT, n 1178
     1100 IU vit D y 1500 mg ca
  Reducción 77% en colon y mama
aumento de 25OH de 28 a 38.4 ng/ml
               Lappe, J. M et al. Am J Clin Nutr 2007;85:1586-1591
Riesgo de cancer Colorectal Cancer invasivo con
suplemento de Calcio y vitamina D (1000/800) vs Placebo
                                                                           WHI
                                                                     N=36,000
                                                                   mujeres 1000
                                                                   mg de calcio
                                                                    400 IU vit D
                                                                         7 años
                                                                   NO reduccion


Problemas: dosis baja, mal cumplimiento, no control de niveles de
25OHD al final del estudio

    Wactawski-Wende J. Calcium plus Vitamin D Supplementation and the Risk of
    Colorectal Cancer. NEJM 354:684
Fibra y cancer colorectal
Conclusions I
• Colorectal cancer is the third most common cancer
  worldwide, with 1.2 million new cases annually
• Intake of dietary fibre and whole grains has been established
  as protective
• It is unclear whether only specific types of fibre or sources of
  fibre are associated with the risk of colorectal cancer
• Intakes of dietary fibre, cereal fibre, and whole grains are
  associated with linear decreases in the risk of colorectal
  cancer
• Evidence of an association between intake of fruit, vegetable,
  or legume fibre and risk of colorectal cancer was lacking
• Intake of dietary fibre, particularly cereal fibre and whole
  grains, was associated with a small reduction in the risk of
  colorectal cancer
Conclusions I
• Epidemiology indicates an inverse correlation
  between high fiber consumption and lower colon
  cancer rates.
• Cereal fiber sources show the most consistent
  negative correlation.
• However, human case-control studies in general fail
  to confirm any protective effect due to dietary fiber.
• Experimental data have in general shown a
  protective effect with supplements of poorly
  fermentable fibers such as wheat bran or cellulose.
Conclusions II
• Because dietary fibers differ in their
  physiochemical properties it has been difficult
  to identify a single mechanism by which fibers
  modify colon carcinogenesis.
• More metabolic and physiological studies are
  needed to fully define the mechanisms by
  which certain fibers inhibit experimental colon
  carcinogenesis.
Thank you very much for
     your attention
Fibra y cancer colorectal

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Fibra y cancer colorectal

  • 1. Fibra y cancer colorectal I Jornada Universitaria UCM-CLAS Mayo 2012 H.G.U.Gregorio Marañón. Cátedra UCM- CLAS Dra. Pilar Riobó Serván Endocrinologia y Nutrición www.doctorariobo.com
  • 2. Denis Parsons Burkitt (1911-1993) Burkitt DP. Epidemiology of cancer of the colon and rectum. Cancer. 1971 Jul;28(1):3-13.
  • 3. Burkitt's observation was followed by numerous case-control studies. • A combined analysis of 13 case-control studies as well as a meta-analysis of 16 case-control studies indicated an inverse association between fiber intake and colorectal cancer. • 10 prospective studies, which avoid the potential for recall and control selection bias, have largely failed to support this association.
  • 4. Associations between consumption of dietary fibre and risk of CRC: Studies are level II evidence. Terry et al,2001 Prospective cohort study of 61 Very low consumption of fruit and 463 women vegetables raises risk of CRC Asano and Meta-analysis (5 randomized Increase in dietary fibre intake does not McLeod, 2002 controlled trials) reduce incidence or recurrence of adenomatous polyps Levi et al, 2001 Case-control study: 286 cases Vegetable fibre appears to be more vs. 550 controls protective against CRC than either fruit or grain fibre Bingham et al, Prospective cohort study of 19 Intake of fibre was inversely related to 2003 978 patients incidence of large-bowel cancer Mai et al, 2003 Prospective cohort study No association between fibre intake and CRC Peters et al,21 Cancer screening trial High dietary fibre lowers risk of adenomas 2003
  • 5. Meat??? • countries that consume a lot of meat and animal fat have the highest rates of CCR • this inversely correlates with the consumption of dietary fiber • The protection that fibre offers could be dependent on the type of fibre – cereals type fibre – Vegetable fibre – Fruit fiber
  • 6. Colorectal cancer incidence lower in Africa Incidence rates : USA: 35.8 cases/ 100,000/year UK: 12/100,000/y (40-44 y); 24/100,000/y (45–49y) Nigeria: 3.4/100,000/year, but increasing incidence: (by the last decade, carcinoma of the colon and rectum moved from the tenth to the fourth position) Relative absence of premalignant conditions like adenomatous polyps in West African
  • 7. Body Mass Index Increases Risk for Colorectal Adenomas (Meta-analysis) 36 independent studies, 29,860 incident cases of CRA. A 5-unit increase in BMI, increased the risk for CRA (relative risk = 1.19) increased risk of CRA in obese was independent of race, sex, adenoma progression, and confounders. The association between increased BMI and risk for CRA was stronger for colon than rectal adenoma. A 5-unit increase in BMI was associated with a 19% increased risk for colorectal adenoma Ben Q. Gastroenterology. 2012 Apr;142(4):762-72.
  • 8. 34,467 women, who had undergone colonoscopy • Fruits and vegetables intake was assessed/2 years, FFQ • 1,720 cases of adenoma were diagnosed (1980 – 1998). • Fruit consumption was inversely related to the risk of polyps, but little association was found for vegetable consumption. – five or more servings of fruit a day had OR: 0.60 for developing colorectal adenomas (P = 0.001). – OR for vegetable consumption was 0.82 (P = 0.1). – four or more servings of legumes per week had a lower incidence of colorectal adenomas (OR, 0.67. P = 0.005).
  • 9. 2818 persons who had undergone colonoscopy. • Self-administered questionnaire from AHS-1, 1976 • outcome was assessed from AHS-2 data (2002 - 2005) • Results: – A total of 441 cases of colon polyps were identified. – total fiber intake was inversely associated with the risk of colon polyps (OR for highest vs lowest quartile 0.71, 95% CI 0.51–0.99). – Vegetables &legumes (OR for highest vs lowest quartile 0.65; p .02). – This association showed a dose-response effect (p .04).
  • 11. Total dietary fiber intake, specifically from vegetables, was inversely associated with colon polyps, with a clear dose-response effect. Fiber intake from fruits and grains did not show a significant effect on colon polyps
  • 12. • Prospective cohort: 59000 African American women • 155,414 person-years of follow-up (1997 to 2007) women who had had at least one colonoscopy • Two dietary patterns, Western and prudent, were utilized – 620 incident cases of colorectal adenomas were identified. Cancer Epidemiol Biomarkers Prev; 20(5); 818–25
  • 13. The highest quintile of prudent diet, relative to the lowest quintile, was significantly associated with 34% lower colorectal adenoma risk (IRR = 0.66; P< 0.01). Higher scores on the Western pattern were associated with a higher risk of developing colorectal adenoma (IRR = 1.42; 95% CI, 1.09–1.85 for the highest quintile relative to the lowest; P = 0.01).
  • 14. Tennessee Colorectal Polyp Study. Participants (40–75 y) colonoscopy from 2003 to 2005. Dietary intake was assessed 764 cases and 1517 controls increased intakes of total fruits, berries, fruit juice, and green leafy vegetables were associated with reduced adenoma risk
  • 15. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (1993–2001) 3057 cases with 1 adenoma 29 413 control subjects. FFQ to quantify intake of fruit and vegetables in the 12 mo before screening Diets rich in fruit and deep-yellow vegetables, dark-green vegetables, and onions and garlic are modestly associated with reduced risk of colorectal adenoma
  • 16. dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer.
  • 17. Prospectively assess the association between the Alternate Mediterranean Diet (aMed) and the DASH-style diet scores and risk of colorectal cancer • A total of 87,256 women and 45,490 men , followed for 26 y. • The aMed and DASH scores were calculated for each participant by using dietary information that was assessed ≤7 times during follow-up. Results: • 1432 cases of incident colorectal cancer among women and 1032 cases in men. • Comparing top with bottom quintiles of the DASH score, the pooled RR for total colorectal cancer was 0.80 (P for trend = 0.0001). • No association was observed with aMed score. • Conclusion: Adherence to the DASH diet (higher intakes of whole grains, fruit, and vegetables; moderate amounts of low-fat dairy; and lower amounts of red or processed meats, desserts, and sweetened beverages) was associated with a lower risk of colorectal cancer.
  • 18. 1.8 million person-years and 1,596 cases of CRC little association with fiber intake
  • 19. European Prospective into Cancer (EPIC) • 519 978 individuals; FFQ in 1992—98 • Follow-up consisted of 1 939 011 person-years, • 1065 reported cases of colorectal cancer • Dietary fibre in foods was inversely related to incidence of CRC • RR for the highest versus lowest quintile of fibre intake was 0·58 • No food source of fibre was more protective than others • Critics: – included various populations, ranging from Scandinavia to the Mediterranean, with diverse dietary habits. – Folate intake was not controlled In populations with low average intake of fibre, an approximate doubling of total fibre intake from foods could reduce the risk of colorectal cancer by 40%.
  • 20. • 45 491 women in the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort. • A 62-item FFQ was administered in 1987-89 and follow-up questionnaires (in 1992–95 and 1995–98) • follow-up time of 8.5 years, • 487 CRC cases • No evidence that dietary fibre intake lowers CRC risk • Critics: cohort of older women characterized by a relatively low fibre intake
  • 22. Fibra de frutas Aune D et al BMJ 2011;343:d6617
  • 23. Fibra de vegetales Aune D et al BMJ 2011;343:d6617
  • 24. Fibra de legumbres Aune D et al BMJ 2011;343:d6617
  • 25. Fibra de cereales Aune D et al BMJ 2011;343:d6617
  • 26. Grano integral Aune D et al BMJ 2011;343:d6617
  • 27. The relative risk of colorectal cancer for each 10 g/day intake was: 0.90 for total fibre 0.93 for fruit fibre 0.98 for vegetable fibre 0.62 for legume fibre 0.90 for cereal fibre In addition to a high total dietary fibre , cereal fibre and whole grains may reduce the risk of CRC The relative risk for an increment of three servings daily of whole grains was 0.83
  • 28. Mechanisms for a reduced risk of colorectal cancer with high fiber intake • high stool bulk, dilution, absorption, and removal of carcinogens, cocarcinogens, and/or tumor promoters • reduces stool transit time ->lowers exposure to potential carcinogens. • bind to bile acids potentially lessening their toxic effects. • Cereal fibre and whole grains are rich in inositol hexaphosphate (IP6) that has been proven to reduce experimental cancers, not just of the CRC but of other organs • fibre is fermented to volatile fatty acids , – protective in experimental models of carcinogenesis. – lowers the pH, which prevents the conversion of primary to secondary bile acids
  • 29. Efectos del butirato sobre el colon • inhibition of inflammation and carcinogenesis, • reinforcing various components of the colonic defence barrier • decreasing oxidative stress. • may promote satiety. • inhibition of nuclear factor kappa B activation • histone deacetylation. Hamer HM. the role of butyrate on colonic function.Aliment Pharmacol Ther. 2008 15;27(2):104-19
  • 30. elevated luminal butyrate as delivered by HAMSB increased the rate of apoptosis but not colonocyte proliferation in the distal colon of rats in acute response toAOM-induced genotoxicity • Proapoptotic function of butyrate plays a major role reducing tumour formation in the AOM-treated rat Carcinogenesis. 2012 January; 33(1): 197–202.
  • 31. Otros factores carcinogenos/ anticarcinogenos
  • 32. Spices and Phytonutrients • Turmeric (curcumin, curry) has anticancer properties – it targets multiple signalling pathways that may protect the colon by decreasing the activity of beta-glucuronidase and mucinase – Other anticancer properties : • inhibition of lipooxygenase activity, specific inhibition of cyclooxygenase 2 expression, and the promotion/progression stages of carcinogenesis [55, 56]. • Garlic and onions, contain diallyl sulphide and flavonoids – suppress cell division in human colon tumor cells – high antioxidant property (due to their wide content of) ; • Red pepper (chili ) has been shown to protect against colorectal carcinoma – The main ingredient of pepper is capsaicin, and this is known to cause death of colon cancer cells.
  • 33. Dietary constituent which may decrease tumor risk in colon and rectum Correa Lima , Nutr Hosp 2005
  • 34. • The EPIC study is a prospective cohort to investigate the associations between dietary, lifestyle, genetic, and environmental factors and risk of specific cancers. • 366,521 women and 153,457 men enrolled between 1992 and 1998 in 10 European countries There is convincing evidence that physical activity reduces colon cancer risk
  • 35. Actividad fisica y cancer de colon Kaiser Permanente Medical Care Program (1997 - 2002) Vigorous physical activity was associated with reduced risk of rectal cancer (OR = 0.60) Participation in vigorous activity over the past 20 years conferred the greatest protection (OR = 0.55, 95% CI: 0.39, 0.78 for men; OR = 0.44, 95% CI: 0.30, 0.67 for women).
  • 36. •Lifestyle index: physical activity, waist, smoking, alcohol, and diet (fibre, fat, red and processed meat, fruits and vegetables) •Follow-up: 9.9 years, 678 persons had CRC diagnosed. • 13% (95% CI 4% to 22%) of CRC were attributable to lack of adherence to one additional recommendation •If all participants had followed the 5 recommendations, 23% (9% to 37%) of CRC might have been prevented.
  • 37. 37,112 persons from Australia, recruited from 1990 to 1994 • 9 years of follow-up • Diet was measured with a FFQ • 283 colon cancers and 169 rectal cancers Consumption of fresh red meat and processed meat seemed to be associated with an increased risk of rectal cancer. Consumption of chicken and fish did not increase risk. Dietary heme injures surface epithelium, hyperproliferation, inhibition of apoptosis and crypt hyperplasia in rat colon Cancer Epidemiol Biomarkers Prev 2004;13(9):1509–14)
  • 38. Daily increase of 100 g of all meat or red meat is associated with a significant 12–17% increased risk of CRC A significant 49% increased risk was found for a daily increase of 25 g of processed meat
  • 39. Heterocyclic amines (HCAs) • Meat cooked at high temperatures contains HCA • Produced when meat is heated above 180°C for long periods, and these HCAs have consistently been identified in well-done meat • Meat grilled or barbecued contains the highest amount of polycyclic aromatic hydrocarbons (PAHs) because of the exposure to smoke formed from the pyrolysis of fatty juices that drip down onto the heat source • The poor electricity supply in most rural and urban areas in Africa does not allow proper refrigeration of meat, thus many households deep-fry meat for preservation and consumption.
  • 40. Netherlands Cohort Study on diet and cancer 2,323 CRC cases, after 13.3 years of follow-up. • Compared to abstaining, alcohol consumption of ≥30.0 g/day (∼3 alcoholic drinks) was positively associated with the risk of CRC (HR: 1.32,). • Cancer risk seemed to increase from proximal colon through rectum; – HR: 1.29, for proximal colon cancer, – HR: 1.41, for distal colon cancer, – HR: 2.07, for rectosigmoid cancer
  • 41. • CRC risk for beer (HR 1.38) was higher than wine (HR 5 1.21) • Higher HRs for baseline alcohol with low levels of folate intake
  • 42. Folate and CRC risk • epidemiologic studies have found an inverse relationship between high intake of folate & CRC risk, but not consistentely • Reduction of 30%-40% in CRC risk for persons with high levels of folate intake compared to those with low levels • The risk of CRC decreases 11% for every 400 μg of folate ingested. • BUT… • Animal studies have suggested that high-dose folic acid might promote colorectal tumorigenesis • A large, placebo-controlled multicenter trial has shown that high- dose folate might increase the risk of neoplastic transformation • A multicenter, randomized, double-blind trial has shown that folate supplementation was found to have no effect on adenoma recurrence [relative risk (RR) = 1.07, 95% CI: 0.85-1.34
  • 43. Folate and CRC risk dietary folate supplementation protection against colonic carcinogenesis might depend on the stage of colorectal carcinogenesis, and would protect against carcinogenesis in normal colorectal tissue, but that folate might enhance pre-existing lesions
  • 44. Vitamina D Actividad anticancer de la vit D? en animales y en líneas celulares durante años. 1,25(OH)2D estimula la expresión de inhibidores del ciclo celular p21 y p27 y de E-cadherina e inhibe la actividad de β-catenina 1,25(OH)2D repara el DNA dañado por UVR Hay evidencias epidemiológicas que apoyan el papel de la vitamina D para la prevención de ciertos canceres, sobre todo mama, colon y prostata.
  • 45. Premature mortality due to cancer in white females, and males as determined on the basis of the July 1992 DNA- weighted ultraviolet B (UV-B) radiation by use of a total ozone mapping spectrometer Holick, M. F Am J Clin Nutr 2004;79:362-371
  • 46. Multivariable relative risks for an increment of 25 nmol/L in predicted plasma 25-hydroxy-vitamin D level for individual cancers in the Health Professionals Follow-up Study (1986-2000) Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. Giovannucci, E. et al. J. Natl. Cancer Inst. 2006 98:451-459; doi:10.1093/jnci/djj101
  • 47. Los individuos con ingesta ≥1000 IU/día de Vitamina D o con niveles séricos ≥33 ng/ml (82 nmol/l) de 25- hydroxyvitamin D tenían una incidencia 50% más bajas de cancer colorectal cancer Son necesarias acciones para aumentar la ingesta de D3 a 1000 IU/día Gorham ED. Vitamin D and prevention of colorectal cancer. J Steroid Biochem Mol Biol 2005;97:179-194.
  • 48. Professionals Health Study 179 casos de cancer Acociacion inversa entre vitamina D y Cancer colorectal
  • 49. 74.000 japoneses No asociacion con vitamina D Pero si con calcio . Ishihara, M. Inoue, M. Iwasaki, S. Sasazuki, and S. Tsugane Dietary calcium, vitamin D, and the risk of colorectal cancer Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1576 - 1583.
  • 50. Interrelationship among risk factors for colon cancer Davis, C. D. et al. J. Natl. Cancer Inst. 2007 99:1563-1565;
  • 51. Cancer PCRT, n 1178 1100 IU vit D y 1500 mg ca Reducción 77% en colon y mama aumento de 25OH de 28 a 38.4 ng/ml Lappe, J. M et al. Am J Clin Nutr 2007;85:1586-1591
  • 52. Riesgo de cancer Colorectal Cancer invasivo con suplemento de Calcio y vitamina D (1000/800) vs Placebo WHI N=36,000 mujeres 1000 mg de calcio 400 IU vit D 7 años NO reduccion Problemas: dosis baja, mal cumplimiento, no control de niveles de 25OHD al final del estudio Wactawski-Wende J. Calcium plus Vitamin D Supplementation and the Risk of Colorectal Cancer. NEJM 354:684
  • 54. Conclusions I • Colorectal cancer is the third most common cancer worldwide, with 1.2 million new cases annually • Intake of dietary fibre and whole grains has been established as protective • It is unclear whether only specific types of fibre or sources of fibre are associated with the risk of colorectal cancer • Intakes of dietary fibre, cereal fibre, and whole grains are associated with linear decreases in the risk of colorectal cancer • Evidence of an association between intake of fruit, vegetable, or legume fibre and risk of colorectal cancer was lacking • Intake of dietary fibre, particularly cereal fibre and whole grains, was associated with a small reduction in the risk of colorectal cancer
  • 55. Conclusions I • Epidemiology indicates an inverse correlation between high fiber consumption and lower colon cancer rates. • Cereal fiber sources show the most consistent negative correlation. • However, human case-control studies in general fail to confirm any protective effect due to dietary fiber. • Experimental data have in general shown a protective effect with supplements of poorly fermentable fibers such as wheat bran or cellulose.
  • 56. Conclusions II • Because dietary fibers differ in their physiochemical properties it has been difficult to identify a single mechanism by which fibers modify colon carcinogenesis. • More metabolic and physiological studies are needed to fully define the mechanisms by which certain fibers inhibit experimental colon carcinogenesis.
  • 57. Thank you very much for your attention