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Diet and Cancer: Can Your Diet Really Reduce Cancer Risk? Tarek Elrafei, D.O. Division Chief, Hematology/Medical Oncology Jacobi Medical Center, Bronx.

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Presentation on theme: "Diet and Cancer: Can Your Diet Really Reduce Cancer Risk? Tarek Elrafei, D.O. Division Chief, Hematology/Medical Oncology Jacobi Medical Center, Bronx."— Presentation transcript:

1 Diet and Cancer: Can Your Diet Really Reduce Cancer Risk? Tarek Elrafei, D.O. Division Chief, Hematology/Medical Oncology Jacobi Medical Center, Bronx NY Assistant Professor Albert Einstein college of Medicine

2 Cancer Prevention Diet –Dietary Fat –Red meat –Fruits and Vegetables –Dairy –Fiber –Glycemic load –Omega-3 fatty acids Vitamins & Micronutrients Alcohol Nutritional support in patients with cancer

3 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 meats If you drink alcoholic beverages, limit consumption. Drink no more than one drink per day for women or two per day for men. American Cancer Society (ACS) Recommendations for Individual Choices CA Cancer J Clin 2006; 56:

4 Whats the evidence? Pubmed search for diet + cancer –27,360 scientific publications Epidemiological, animal studies, retrospective, prospective observational studies, clinical trials –961 Randomized controlled trials –128 Meta-analysis –32 practice guidelines Pubmed search for Fava beans and cancer???

5 While we have come a long way since this 1940s Advertisement, we still can not identify who will and will not benefit from dietary intervention strategies

6 Dietary Fat No clear link between total fat intake and colon or breast cancer –Womens Health Initiative Dietary Modification Trial 48,835 women followed for 8 years –Behavioral modification program to reduce dietary fat: reduced % calories consumed as fat 10.7% year 1 and 8 % at year 6 –vs.usual diet control group –No difference in incidence of colon cancer; a trend towards decreased breast cancer Prostate cancer –Large 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 illnesses 14,916 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

8 Adjusted RR of nonaggressive prostate cancer by control quintiles of total 18:2n-6 trans-fatty acids according to baseline BMI (A) and random aspirin assignment (B). Chavarro J E et al. Cancer Epidemiol Biomarkers Prev 2008;17: ©2008 by American Association for Cancer Research

9 Red Meat Heme content, animal fat, carcinogens when meat is cooked at high temperatures suggested to increase cancer risk High 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 professionals 205 cases of colon cancer after 6 years of follow up Intakes of total fat, saturated fat, and animal fat were not related to risk of colon cancer Men 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 month Other 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 up After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer The 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 month »Processed 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 meat European Prospective Investigation into cancer and nutrition (EPIC study) – men and women from 10 European countries between 1992 and –1329 incident colorectal cancers were documented after a mean follow-up of 4.8 years –colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake

12 Fruits and Vegetable A large number of potentially anticarcinogenic agents are found in fruits and vegetables Retrospective 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 women –Flavonoids (tomatoes, green peppers, berries, and citrus fruits) may decrease breast cancer –Lycopene (tomatoes) may decrease prostate cancer

13 Epidemiologic Studies of Lycopene and Cancer Risk Cancer Type of Study Reference Breast CohortDorgan et al. Can Cau Cont 9: 89-97, 1998 Colon Case-controlFranceschi et al. Int J Cancer 72:56-61, 1997 Lung Case-controlAgudo et al. Eur J Cancer 33: , 1997 Prostate CohortGiovannucci et al. J Natl. Cancer Inst. 87: , 1995

14 Soy Intake and Cancer Concerns Growth enhancement of human mammary tumors transplanted into mice that were fed soy or isoflavonids (Hsieh, et al. Cancer Res. 58:3833, 1998). 17 of 26 animal studies reveal soy or soybean isoflavones reduce tumor tumor development 19 or 21 human epidemiological studies provide evidence of protection against cancer, especially rectal and stomach cancers (1 study reported increase)

15 Soymilk Intake & Prostate Cancer Risk Cancer Causes and Control 9: 553, <11>1 confidence interval Daily Intake (servings) Relative Risk *

16 Fruits and Vegetables Large 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 Interpretations –there 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 effects –Additionally, exposures in childhood may be more important in the development of cancer than exposures later in life –It is possible that intake of specific fruits and vegetables may have effects on specific cancers.

17 Tomato Varieties Compounds Types of Bioactive Compounds May Vary with New Varieties

18 Dairy A 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 foods Netherlands 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 Study –88,000 women –Breast cancer risk inversely associated with Low-fat dairy, calcium (from dairy) and vitamin D (non-dairy intake) in premenopausal women but not postmenopausal Pooled analysis of 8 prospective studies confirm no association between dairy and breast cancer in postmenopausal women –351,041 women, 7379 of whom were diagnosed with invasive breast cancer during up to 15 years of follow- up Int J Epidemiol Feb;31(1):78-85

20 Dairy Dairy Food, Calcium, and Risk of Cancer in the NIH-AARP Diet and Health Study –Calcium 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 71 –A 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 Cancer The 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 period Similarly, 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 factors –One 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 itself –Diet-Gene interactions

22 Diet-Gene Interactions in Colon Cancer *(high fat and phosphate, low calcium and vitamin D) Yang et al, Cancer Res. 61, 565, Weeks Percent survival p21+/+ AIN-76A Diet p21+/- AIN-76A Diet p21-/- AIN-76A Diet p21+/+ *Western Diet p21+/- Western Diet p21-/- *Western Diet

23 Glycemic Load Glycemic load is a function of glycemic index, carbohydrate content per serving, and frequency of intake –Glycemic Index = how rapidly and to what extent blood glucose levels rise Insulin and Insulin like growth factors promote cell proliferation and possibly certain cancers 15 studies (2.5 million patients) estimate 30% higher risk of colon cancer among diabetics

24 Glycemic Load NIH-AARP Diet and Health Study –7 years of follow up –found no association in 15,000 cancers in women and 33,000 cancers cases in men Womens Health Study –174 colon cancers in 38,451 women with a calculated 2.85 increased risk Canadian trial – women participating in a randomized, controlled trial of screening for breast cancer in Canada –16.5 years of follow-up, 616 incident cases of colorectal cancer and no association of increased risk with higher glycemic index Nurses Health Study & Health Professionals Follow up Studies –20 years of follow-up. 1,809 incident colorectal cancers – found no association for women but an increased risk for men of colon cancer

25 Omega-3 Fatty Acids Individual studies have found increased and decreased risk of cancer with no consistent pattern Systematic Review of all prospective trials revealed no association between Omega- 3 FA and cancer –20 cohorts from 7 countries for 11 different cancer types –700,000 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"

27

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/d Vitamin E 400 mg/d Vitamin EPlacebo Selenium 7 + Years Treatment Endpoint Prostate Cancer Incidence

29 SELECT Trial SELECT 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 absorption Prostate and Breast Cancer: Vit. D + calcium showed no effect on breast cancer in 3 trials One randomized prospective trial of calcium + vit D in 1179 women over 4 years has shown decrease in all cancer types

31 Am J Clin Nutr Mar;87(3):794

32 Alcohol

33

34 Obesity and EBC Outcomes Obesity (BMI > 30) associated with poorer DFS and OS in operable breast cancer Evaluation of women with EBC in adjuvant trials of doxorubicin, cyclophosphamide plus other agents to determine relationship between obesity and –Clinical characteristics –Clinical outcomes –Clinical outcomes and breast cancer subtype ER/PgR-positive, HER2-negative disease HER2-positive disease Triple-negative disease

35 ECOG Trials Included in Analysis E1199E5188E3189 PopulationNode positive High-risk node negative ER positive Node positive Premenopausal ER negative PgR negative Node positive ChemotherapyCyclophosphamide, doxorubicin, taxane Cyclophosphamide, doxorubicin, fluorouracil Cyclophosphamide, doxorubicin, fluorouracil vs 16-wk regimen Endocrine therapy Tamoxifen ± aromatase inhibitor None vs goserelin vs goserelin + tamoxifen None Patients with BMI data, n

36 Obesity and Outcomes in Subgroup Analysis of E1199 E1199 Subgroup DFSOS HR (95% CI) P Value HR (95% CI) P Value ER and/or PgR positive, HER2 negative 1.23 ( ) ( ).002 ER, PgR, HER2 negative (n = 708) 1.01 ( ) ( ).75 HER2 positive (n = 661) 1.07 ( ) ( ).55 Sparano J, et al. SABCS Abstract S2-1.

37 Validation by Analysis of Trial Data From E5188 and E3189 TrialDFSOS HR (95% CI) P Value HR (95% CI) P Value E5188 (ER/PgR positive, HER2 negative) 1.41 ( )< ( )<.0001 E3189 (ER negative)0.90 ( ) ( ).18 Sparano J, et al. SABCS Abstract S2-1.

38 Nutritional support in patients with cancer Ginger Vitamin 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, or –4) 1.5g ginger All doses of ginger significantly reduced nausea (p=0.003) compared to placebo.

40 Vitamin E Inhibits Cisplatin-Induced Apoptosis in MCF-7 Breast Cancer Cells. Salganik, et al. Carcinogenesis 21: 909, Control ECPCP+E % Apoptosis +* ** Antioxidant reduces efficacy of cisplatin

41 TABLE 1 American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention American Cancer Society (ACS) Recommendations for Individual Choices Maintain 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 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 meats If you drink alcoholic beverages, limit consumption. Drink no more than one drink per day for women or two per day for men. American Cancer Society (ACS) Recommendations for Individual Choices CA Cancer J Clin 2006; 56:

43 Fruits 1 medium apple, banana, orange 1/2 cup of chopped, cooked, orcanned fruit 1/2 cup of 100% fruit juice Vegetables 1 cup of raw leafy vegetables 1/2 cup of other cooked or raw vegetables, chopped 1/2 cup of 100% vegetable juice Grains 1 slice bread 1 ounce ready-to-eat cereal 1/2 cup of cooked cereal, rice, pasta What Counts as a Serving?

44 Beans and nuts 1/2 cup cooked dry beans 2 tablespoons peanut butter 1/3 cup nuts Dairy foods and eggs 1 cup milk or yogurt 1 1/2 ounces of natural cheese 2 ounces processed cheese 1 egg Meats2–3 ounces of cooked lean meat, poultry, fish

45 Conclusions Inconsistencies in results of nutritional studies –Observational studies Imprecise diet recall Confounding cancer risk factors –Randomized studies Poor adherence to dietary intervention Insufficient follow up time Wrong dose or form of nutrient Study population may be replete with in nutrient studied One 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 risk –Low fat diet may decrease risk –Low fat dairy, calcium, Vit D (in premenopausal) –Folic acid may decrease risk No difference –Red meat –Dietary fat –Fruits and Vegetables –Vitamin D and Calcium (in postmenopausal) Increased Risk –Alcohol (2 or more drinks)

47 Conclusions by Tumor Type: Prostate Cancer Increased risk –large amounts of alpha-linoleic acid and low amounts of linoleic acid increase risk of nonaggresive cancers –Calcium? No difference –Selenium –Vitamin E Decreased risk –Soy milk?

48 Conclusions by tumor type: Colon cancer Decreased Risk –Fish (men and women) –Chicken without skin (women) –Calcium and Dairy (men and women)Red meat increases risk in men and women No difference –Fiber Increased Risk –Red meat (men and women) –Processed meat –Liver –High glycemic load (men and women)

49 Conclusions by tumor type: Ovarian cancer –Dairy may increase risk?? All cancers –Calcium + vit D

50 Just when I knew all of lifes answers, They changed all the questions!!

51 Lifestyle changes

52 Caloric Restriction in Yeast causes silencing of genes and extended life span (Guarente and Kenyon Nature 2000; 408:255

53 Colon Cancer and Exercise

54 More is Not Always Better: Energy Intakes and Expenditures Are Linked to Health!

55 Caffeine

56 Tea (Camellia sinensis) Green Tea Black Tea 30-40% Catechins 3-6% Caffeine ~310 mg polyphenols per 6 ounces 3-10% Catechins 2-6% Theaflavins > 20% Thearubigens 3-6% Caffeine ~340 mg polyphenols per 6 ounces Dried Tea Leaves Crushed tea leaves Polyphenol oxidase Oxidation, Polymerization O OR 2 HO OH R 1 HO Yang CS. Personal Communication

57 Tea and Cancer Prevention Camellia Sinensis Yang CS. Personal Communication Skin Liver Colon Oral Esophagus Lung Stomach Prostate Mammary

58 < 300 mgCaffeine> 300 mg Vitamin D Receptor Genotype TT Tt tt Spine Bone Mass Density (%) Influence of Caffeine on Bone Mass May Depend on Genes Rapuri et al. Am J Clin Nutr 2001 Nov;74(5):

59 Recent 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 Fleischauer, et al. Amer JClin Nutr 72, 1047, Steinmetz et al. Amer. J. Epidemiology 139:1, 1994 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, 1994

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: This 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 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 PlaceboRR 97% CI Skin Cancer Squamous cell Basal cell Cancer (- Skin) Lung Prostate Colorectal Breast All Sites (- Skin) Selenium & Skin Cancer Prevention Trial Clark et al. JAMA 276: 1957, Phase III trial with 1,312 skin cancer subjects Se (200 g) as Brewers Yeast vs. Placebo, follow-up 6.4 yrs

62 Effects of Microwave Heating of Garlic on Total DMBA-Induced DNA Adducts a b b DNA Adducts (nmol Adducts/mol DNA) Control Peel/ Crushed 30 seconds 60 seconds Microwave/ Peel/ Crushed a Song and Milner J Nutr 1999;129:657-61

63 150 mg 3 grams 150 grams MARKET STAGE BROCCOLI 3-DAY SPROUTS FREEZE-DRIED SPROUT EXTRACT All preparations contain the same quantity of detoxification enzyme inducer activity, (Glutathione S-transferase and Quinone Reductase) How Should We Consume Bioactive Food Components?


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