Presentation on theme: "Diet and Cancer: Can Your Diet Really Reduce Cancer Risk?"— Presentation transcript:
1 Diet and Cancer: Can Your Diet Really Reduce Cancer Risk? Tarek Elrafei, D.O.Division Chief, Hematology/Medical OncologyJacobi Medical Center, Bronx NYAssistant ProfessorAlbert Einstein college of Medicine
2 Cancer Prevention Diet Vitamins & Micronutrients Alcohol Dietary FatRed meatFruits and VegetablesDairyFiberGlycemic loadOmega-3 fatty acidsVitamins & MicronutrientsAlcoholNutritional support in patients with cancer
3 American Cancer Society (ACS) Recommendations for Individual Choices Consume a healthy diet, with an emphasis on plant sources.Choose foods and beverages in amounts that help achieve and maintain a healthy weight.Eat five or more servings of a variety of vegetables and fruits each day.Choose whole grains in preference to processed (refined) grains.Limit consumption of processed and red meatsIf you drink alcoholic beverages, limit consumption.Drink no more than one drink per day for women or two per day for men.CA Cancer J Clin 2006; 56:
4 What’s the evidence? Pubmed search for “diet + cancer” 27,360 scientific publicationsEpidemiological, animal studies, retrospective, prospective observational studies, clinical trials961 Randomized controlled trials128 Meta-analysis32 practice guidelinesPubmed search for “Fava beans and cancer”???
5 While we have come a long way since this 1940’s Advertisement, we still can not identify who will and will not benefit from dietary intervention strategies
6 Dietary FatNo clear link between total fat intake and colon or breast cancerWomens Health Initiative Dietary Modification Trial48,835 women followed for 8 yearsBehavioral modification program to reduce dietary fat: reduced % calories consumed as fat 10.7% year 1 and 8 % at year 6vs.“usual diet” control groupNo difference in incidence of colon cancer; a trend towards decreased breast cancerProstate cancerLarge amounts of alpha linoleic acid and low linoleic acid increase risk (red meats and dairy)Mechanism of association may be lower testosterone levels on men who decrease fat intake
7 Physicians Health Study randomized trial of aspirin and β-carotene (vs. placebo)22,071 U.S. male physicians, ages 40 to 84 in 1982, without a history of cardiovascular disease, cancer, or other major illnesses14,916 U.S. male physicians provided plasma samples, which were frozen at -82 degrees C:Blood levels of all the trans-fatty acids examined for the 120 men who developed prostate cancer
9 Red MeatHeme content, animal fat, carcinogens when meat is cooked at high temperatures suggested to increase cancer riskHigh intake of red meat including beef, pork, veal, and lamb, is associated with an elevated risk of colorectal cancer in both men and women in 6 studies…prospective study 47,949 U.S. male health professionals205 cases of colon cancer after 6 years of follow upIntakes of total fat, saturated fat, and animal fat were not related to risk of colon cancerMen who ate beef, pork, or lamb as a main dish five or more times per week had a relative risk of 3.57 compared to men eating these foods < once per monthOther sources of animal fat, including dairy products, poultry, and fish as well as vegetable fat, were slightly inversely related to risk of colon cancer.No clear association existed between fiber or vegetable intake and risk of colon cancer.
10 Red Meat prospective study 88,751 women 34 to 59 years 150 cases of colon cancer after 6 years of follow upAfter adjustment for total energy intake, animal fat was positively associated with the risk of colon cancerThe relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 as compared with those reporting consumption < once a monthProcessed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk.A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake
11 Red meatEuropean Prospective Investigation into cancer and nutrition (EPIC study)men and women from 10 European countries between 1992 and 1998.1329 incident colorectal cancers were documented after a mean follow-up of 4.8 yearscolorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake
12 Fruits and VegetableA large number of potentially anticarcinogenic agents are found in fruits and vegetablesRetrospective studies and small prospective studies have suggested a dose-response relationship between fruit and vegetable intake and the prevention of cancers.Soy decreases prostate cancer in men and breast cancer in Asian womenFlavonoids (tomatoes, green peppers, berries, and citrus fruits) may decrease breast cancerLycopene (tomatoes) may decrease prostate cancer
13 Epidemiologic Studies of Lycopene and Cancer Risk Cancer Type of Study ReferenceBreast Cohort Dorgan et al Can Cau Cont 9: 89-97, 1998Colon Case-control Franceschi et al Int J Cancer 72:56-61, 1997Lung Case-control Agudo et al Eur J Cancer 33: , 1997Prostate Cohort Giovannucci et al J Natl. Cancer Inst. 87: ,
14 Soy Intake and Cancer Concerns 17 of 26 animal studies reveal soy or soybean isoflavones reduce tumor tumor development19 or 21 human epidemiological studies provide evidence of protection against cancer, especially rectal and stomach cancers (1 study reported increase)ConcernsGrowth enhancement of human mammary tumors transplanted into mice that were fed soy or isoflavonids (Hsieh, et al. Cancer Res. 58:3833, 1998).13
15 Soymilk Intake & Prostate Cancer Risk 1.00.90.8Relative Risk0.3*225 incident cases of prostate cancer in 12,395 California Seventh-Day Adventist menFrequent consumption (more than once a day) of soy milk was associated with 70 per cent reduction of the risk of prostate cancer (relative risk=0.3, 95 percent confidence interval , p-value for linear trend=0.03). The association was upheld when extensive adjustments were performedOur study suggests that men with high consumption of soy milk are at reduced risk of prostate cancer. Possible associations between soy bean products, isoflavones and prostate cancer risk should be further investigated<11>1confidence intervalDaily Intake (servings)Cancer Causes and Control 9: 553, 1998
16 Fruits and VegetablesLarge prospective studies have not found such a benefit:71,910 women from the Nurses' Health Study and 37,725 men in the Health Professionals' Follow-up Study found no association between fruit and vegetable intake and risk of cancer (for an increment of five servings daily, relative risk [RR] 1.00, 95% CI 0.95 to 1.05)The European Prospective Investigation into Cancer and Nutrition (EPIC) study examined the association between fruit and vegetable intake and risk of breast cancer in 285,526 women ages 25 to 70.Comparing highest and lowest quintiles, there was no association with intake of fruits (RR 1.09, 95% CI ) or vegetables (RR 0.98, CI ).Conclusions and Interpretationsthere is a long lag time between exposures and the development of cancer, during which time individuals may change their diets, limiting the power of studies to detect effectsAdditionally, exposures in childhood may be more important in the development of cancer than exposures later in lifeIt is possible that intake of specific fruits and vegetables may have effects on specific cancers.
17 Types of Bioactive Compounds May Vary with New Varieties Tomato Varieties
18 DairyA meta-analysis of 21 studies evaluating the relationship of dairy food intake and ovarian cancer found no evidence of association in case control studies (RR 0.96) but…Of 4 prospective cohort studies, 3 did demonstrate increased risk of ovarian cancer with high intake of dairy foodsNetherlands Cohort Study on Diet and Cancer.postmenopausal women participating in the Netherlands Cohort Study.After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer cases with no association
19 Dairy Intake and Breast Cancer Nurses Health Study88,000 womenBreast cancer risk inversely associated with Low-fat dairy, calcium (from dairy) and vitamin D (non-dairy intake) in premenopausal women but not postmenopausalPooled analysis of 8 prospective studies confirm no association between dairy and breast cancer in postmenopausal women351,041 women, 7379 of whom were diagnosed with invasive breast cancer during up to 15 years of follow-upInt J Epidemiol Feb;31(1):78-85
20 DairyDairy Food, Calcium, and Risk of Cancer in the NIH-AARP Diet and Health StudyCalcium intake, as determined by a food frequency questionnaire, was associated with decreased total cancer risk over seven years in women, but not in men, in a large US cohort of 567,000 participants aged 50 to 71A decrease in cancers of the digestive tract (particularly colon cancer) with higher dairy food and calcium intake was noted in both men and women
21 Fiber and CancerThe relationship between fiber intake and colorectal cancer risk is unsettled.No relationship was noted in the large observational Nurses' Health Study (N Engl J Med 1999 Jan 21;340(3): ).In contrast, some large observational studies have found a reduced risk of colorectal adenomas and cancer with increased fiber intake.A systematic review of five studies involving a total of 4349 patients concluded that there was no definitive evidence that increased dietary fiber reduces the incidence or recurrence of adenomatous polyps within a two- to four-year periodSimilarly, a pooled analysis of 13 prospective cohort studies (involving 725,628 men and women followed for 6 to 20 years) found that dietary fiber intake was inversely associated with the risk of colorectal cancer but the association was no longer apparent after accounting for other dietary risk factorsOne possible explanation is that the sources of dietary fiber differed across the various study populations.Other possible explanations are that the fiber intake in the Nurses' Health Study was relatively low even in the participants in the highest quintile of intake, or that dietary fiber is a marker for the intake of fruits, vegetables, and grains but is not actually protective in and of itselfDiet-Gene interactions
22 Diet-Gene Interactions in Colon Cancer p21+/+ AIN-76A Diet100p21+/- AIN-76A Diet9080p21+/+ *Western Diet70p21-/- AIN-76A Diet60p21+/- Western DietPercent survival5040p21-/- *Western DietElimination of both alleles of the gene that encodes the cyclin kinase inhibitor p21WAF1/cip1 increases the frequency and size of intestinal tumors in Apc1638+/− mice that inherit a mutant allele of the Apc gene, and intermediate effects are seen if a single p21 allele is inactivated. The increased tumor formation is associated with altered cell maturation in the intestinal mucosa of the p21-deficient mice—increased cell proliferation, and decreased apoptosis, and goblet cell differentiation—that is also a function of p21 gene dosage. "AIN" stands for "American Institute of Nutrition," which is now known as the America Society for Nutritional Sciences. They have published purified diet formulas that are well-accepted and respected in the scientific community as sound general nutrition for laboratory rodents.AIN-76A. The original AIN-76 diet was soon modified by AIN-76A, which increased the vitamin K tenfold. AIN-76A has been used in research for more than 25 years.Moreover, a Western-style diet that mimics principal risk factors for colon cancer (high fat and phosphate, low calcium and vitamin D) accelerates tumor formation in Apc1638+/− mice, and the loss of a single or both p21 alleles is additive with the tumor-promoting effects of this diet, resulting in more and larger tumors, and a highly significant decrease in survival time. Thus, p21 normally suppresses Apc-initiated tumor formation and is haplo-insufficient in this regard. This is consistent with recent reports that Apc initiates tumor formation by up-regulating c-myc expression through alteredβ -catenin-Tcf signaling and that c-myc then up-regulates cdk4, whose activity is inhibited by p21. Decreased expression of p21 is also a marker of poor prognosis in patients, and the data presented suggest that dietary alterations in patients undergoing treatment for colon cancer might be highly effective in improving outcome.302010*(high fat and phosphate, low calcium and vitamin D)4812162024283236WeeksYang et al, Cancer Res. 61, 565, 2001
23 Glycemic LoadGlycemic load is a function of glycemic index, carbohydrate content per serving, and frequency of intakeGlycemic Index = how rapidly and to what extent blood glucose levels riseInsulin and Insulin like growth factors promote cell proliferation and possibly certain cancers15 studies (2.5 million patients) estimate 30% higher risk of colon cancer among diabetics
24 Glycemic Load NIH-AARP Diet and Health Study Women’s Health Study 7 years of follow upfound no association in 15,000 cancers in women and 33,000 cancers cases in menWomen’s Health Study174 colon cancers in 38,451 women with a calculated 2.85 increased riskCanadian trialwomen participating in a randomized, controlled trial of screening for breast cancer in Canada16.5 years of follow-up, 616 incident cases of colorectal cancer and no association of increased risk with higher glycemic indexNurse’s Health Study & Health Professionals Follow up Studies20 years of follow-up. 1,809 incident colorectal cancersfound no association for women but an increased risk for men of colon cancer
25 Omega-3 Fatty AcidsIndividual studies have found increased and decreased risk of cancer with no consistent patternSystematic Review of all prospective trials revealed no association between Omega-3 FA and cancer20 cohorts from 7 countries for 11 different cancer types700,000 patients
26 Vitamins and Micronutrients National Institutes of Health (NIH) consensus conference panel concluded that…"present evidence is insufficient to recommend either for or against the use of multivitamin supplements by the American public to prevent chronic disease"
28 Prostate Cancer Prevention Selenium and Vitamin E Cancer Prevention Trail (SELECT) ($175M)35,000 men, age >55 (> 50 for Black Men)Selenium 200 ug/dVitamin E 400 mg/dSeleniumVitamin EPlacebo7 + Years TreatmentEndpoint Prostate Cancer Incidence
29 SELECT TrialSELECT stands for the Selenium and Vitamin E Cancer Prevention Trial, a prevention clinical trial to see if one or both of these dietary supplements prevent prostate cancer.SELECT is continuing to evaluate the effects of the supplements but participants are no longer taking study supplements. The independent Data and Safety Monitoring Committee for the trial found that selenium and vitamin E, taken alone or together for an average of five and one-half years, did not prevent prostate cancer.The SELECT data showed two concerning, but not statistically significant, trends: there were slightly more cases of prostate cancer in men taking only vitamin E and slightly more cases of diabetes in men taking only selenium. Neither of these findings proves an increased risk from the supplements and may be due to chance.
30 Vitamins and Micronutrients Vitamin D may reduce colon cancer risk by improving calcium absorptionProstate and Breast Cancer: Vit. D + calcium showed no effect on breast cancer in 3 trialsOne randomized prospective trial of calcium + vit D in 1179 women over 4 years has shown decrease in all cancer types
34 Obesity and EBC Outcomes Obesity (BMI > 30) associated with poorer DFS and OS in operable breast cancerEvaluation of women with EBC in adjuvant trials of doxorubicin, cyclophosphamide plus other agents to determine relationship between obesity andClinical characteristicsClinical outcomesClinical outcomes and breast cancer subtypeER/PgR-positive, HER2-negative diseaseHER2-positive diseaseTriple-negative diseaseFor more information on this study, go online to:34
35 ECOG Trials Included in Analysis PopulationNode positiveHigh-risk node negativeER positivePremenopausalER negativePgR negativeChemotherapyCyclophosphamide, doxorubicin, taxaneCyclophosphamide, doxorubicin, fluorouracilCyclophosphamide, doxorubicin, fluorouracil vs wk regimenEndocrine therapyTamoxifen ± aromatase inhibitorNone vs goserelin vs goserelin + tamoxifenNonePatients with BMI data, n34841502613For more information on this study, go online to:35
36 Obesity and Outcomes in Subgroup Analysis of E1199 E SubgroupDFSOSHR (95% CI)P ValueER and/or PgR positive, HER2 negative1.23 ( ).0351.46 ( ).002ER, PgR, HER2 negative (n = 708)1.01 ( ).931.05 ( ).75HER2 positive (n = 661)1.07 ( ).700.89 ( ).55For more information on this study, go online to:Sparano J, et al. SABCS Abstract S2-1.36
37 Validation by Analysis of Trial Data From E5188 and E3189 DFSOSHR (95% CI)P ValueE5188 (ER/PgR positive, HER2 negative)1.41 ( )< .00011.51 ( )E3189 (ER negative)0.90 ( ).410.83 ( ).18For more information on this study, go online to:Sparano J, et al. SABCS Abstract S2-1.37
38 Nutritional support in patients with cancer GingerVitamin E effects on chemotherapy
39 Supportive care for those with cancer Ginger for chemotherapy-related nausea in cancer patients: A URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients. J Clin Oncol 27:15s, 2009 (suppl; abstr 9511)Patients were randomized into four arms:1) placebo,2) 0.5g ginger,3) 1.0g ginger, or4) 1.5g gingerAll doses of ginger significantly reduced nausea (p=0.003) compared to placebo.
40 Antioxidant reduces efficacy of cisplatin Vitamin E Inhibits Cisplatin-Induced Apoptosis in MCF-7 Breast Cancer Cells.6 -Antioxidant reduces efficacy of cisplatin4 -% Apoptosis +**2 -*0 -ControlECPCP+ESalganik, et al. Carcinogenesis 21: 909, 2000.
41 American Cancer Society (ACS) Recommendations for Individual Choices TABLE 1 American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer PreventionAmerican Cancer Society (ACS)Recommendations for Individual ChoicesMaintain a healthy weight throughout life.Balance caloric intake with physical activity.Avoid excessive weight gain throughout the life cycle.Achieve and maintain a healthy weight if currently overweight or obese.Adopt a physically active lifestyle.Adults: engage in at least 30 minutes of moderate to vigorous physical activity, above usual activities, on 5 or more days of the week. Forty-five to 60 minutes of intentional physical activity are preferable.Children and adolescents: engage in at least 60 minutes per day of moderate to vigorous physical activity at least 5 days per week.CA Cancer J Clin 2006; 56:
42 American Cancer Society (ACS) Recommendations for Individual Choices Consume a healthy diet, with an emphasis on plant sources.Choose foods and beverages in amounts that help achieve and maintain a healthy weight.Eat five or more servings of a variety of vegetables and fruits each day.Choose whole grains in preference to processed (refined) grains.Limit consumption of processed and red meatsIf you drink alcoholic beverages, limit consumption.Drink no more than one drink per day for women or two per day for men.CA Cancer J Clin 2006; 56:
43 What Counts as a Serving? Fruits1 medium apple, banana, orange1/2 cup of chopped, cooked, orcanned fruit1/2 cup of 100% fruit juiceVegetables1 cup of raw leafy vegetables1/2 cup of other cooked or raw vegetables, chopped1/2 cup of 100% vegetable juiceGrains1 slice bread1 ounce ready-to-eat cereal1/2 cup of cooked cereal, rice, pasta
44 What Counts as a Serving? Beans and nuts1/2 cup cooked dry beans2 tablespoons peanut butter1/3 cup nutsDairy foods and eggs1 cup milk or yogurt1 1/2 ounces of natural cheese2 ounces processed cheese1 eggMeats2–3 ounces of cooked lean meat, poultry, fish
45 Conclusions Inconsistencies in results of nutritional studies Observational studiesImprecise diet recallConfounding cancer risk factorsRandomized studiesPoor adherence to dietary interventionInsufficient follow up timeWrong dose or form of nutrientStudy population may be replete with in nutrient studiedOne consistent finding is that excess calories from any source leads to weight gain and increased risk of multiple cancers
46 Conclusions by tumor type: Breast Cancer Decreased riskLow fat diet may decrease riskLow fat dairy, calcium, Vit D (in premenopausal)Folic acid may decrease riskNo differenceRed meatDietary fatFruits and VegetablesVitamin D and Calcium (in postmenopausal)Increased RiskAlcohol (2 or more drinks)
47 Conclusions by Tumor Type: Prostate Cancer Increased risklarge amounts of alpha-linoleic acid and low amounts of linoleic acid increase risk of nonaggresive cancersCalcium?No differenceSeleniumVitamin EDecreased riskSoy milk?
48 Conclusions by tumor type: Colon cancer Decreased RiskFish (men and women)Chicken without skin (women)Calcium and Dairy (men and women)Red meat increases risk in men and womenNo differenceFiberIncreased RiskRed meat (men and women)Processed meatLiverHigh glycemic load (men and women)
49 Conclusions by tumor type: Ovarian cancerDairy may increase risk??“All cancers”Calcium + vit D
50 Just when I knew all of life’s answers, They changed all the questions!!
57 Tea and Cancer Prevention SkinLiverCamellia SinensisColonOralEsophagusProstateMammaryStomachLungYang CS. Personal Communication
58 Influence of Caffeine on Bone Mass May Depend on Genes 6< 300 mgCaffeine> 300 mgD Spine Bone Mass Density (%)-6BACKGROUND: The role of caffeine as a risk factor for bone loss is controversial. OBJECTIVE: Our goals were 1) to compare in both a cross-sectional study and a 3-y longitudinal study the bone mineral density (BMD) of postmenopausal women consuming high or low amounts of caffeine and 2) to study the interaction between caffeine intake, vitamin D receptor (VDR)polymorphism, and BMD in the longitudinal study. DESIGN: The results are derived from cross-sectional measurements of BMD in 489 elderly women (aged y) and from longitudinal measurements made in 96 of these women who were treatedwith a placebo for 3 y. Changes in BMD were adjusted for confounding factors and were compared between groups with eitherlow (< or =300 mg/d) or high (>300 mg/d) caffeine intakes and between the VDR genotype subgroups of the low- andhigh-caffeine groups. RESULTS: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes ( /- 0.97% compared with /- 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of boneloss at the spine ( /- 2.62%) than did women with the TT genotype ( /- 1.42%) when their caffeine intake was>300 mg/d. CONCLUSIONS: Intakes of caffeine in amounts >300 mg/d ( approximately 514 g, or 18 oz, brewed coffee) accelerate bone loss at the spine in elderly postmenopausal women. Furthermore, women with the tt genetic variant of VDRappear to be at a greater risk for this deleterious effect of caffeine on bone.-12TT Tt ttTT Tt ttVitamin D Receptor GenotypeRapuri et al. Am J Clin Nutr 2001 Nov;74(5):
59 Prospective cohort study with 41,837 women age 55 to 69, examined 127 food items. “The strongest association in the present study was that for garlic consumption, with an approximate 50% lesser risk associated with high consumption.” Steinmetz et al. Amer. J. Epidemiology 139:1, 1994Recent meta-analysis of Data from 11 trials concluded The random-effects relative risk (RR) estimate for raw and cooked garlic and colorectal cancer was 0.69 and for stomach was 0.53.Fleischauer, et al. Amer JClin Nutr 72, 1047, 2000.
60 Linking diet, religion and cancer Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 21172This study was done to see cancer incidence in children of Jain religion as compared to other religions at a single centre.Jain religion does not consume garlic and onion due to religious belief.retrospective analysis of consecutive children less than 16 years of age diagnosed with cancer at Sir Ganga Ram Hospital from January 2005 to January 2007.Incidence of cancer in children of different religions is similar to that of proportions of population of different religions in Delhi except for Jain religion where incidence of cancer is 6 times higher despite lesser number children in 0-6 year in this population as compared to other religions .Major difference is the diet lacking in onion and garlic .Other reason could be increased literacy levels in Jain community .“This link between diet ,religion and cancer in Jain population needs to be studied in a larger muticenteric setting as it has implications for the whole world.”
61 Selenium & Skin Cancer Prevention Trial Phase III trial with 1,312 skin cancer subjectsSe (200 mg) as Brewers Yeast vs. Placebo, follow-up 6.4 yrsSelenium Placebo RR 97% CISkin CancerSquamous cellBasal cellCancer (- Skin)LungProstateColorectalBreastAll Sites (- Skin)Clark et al. JAMA 276: 1957, 1996.
62 Effects of Microwave Heating of Garlic on Total DMBA-Induced DNA Adducts 100030 secondsa60 secondsa750(nmol Adducts/mol DNA)DNA Adducts500bb250Peel/CrushedControlMicrowave/ Peel/CrushedSong and Milner J Nutr 1999;129:657-61
63 How Should We Consume Bioactive Food Components? MARKET STAGE BROCCOLI3-DAY SPROUTS3 gramsFREEZE-DRIEDSPROUT EXTRACT150 grams150 mgAll preparations contain the same quantity of detoxification enzyme inducer activity, (Glutathione S-transferase and Quinone Reductase)