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Diet and Cancer: Can Your Diet Really Reduce Cancer Risk?

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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 Vitamins & Micronutrients Alcohol
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 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 meats If 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 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 1940’s 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). 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). Adjusted for matching factors: age, smoking status at baseline, and length of follow-up; †, P < 0.05, when compared with men in the lowest quintile. Chavarro J E et al. Cancer Epidemiol Biomarkers Prev 2008;17:95-101 ©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 1998. 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 Cohort Dorgan et al Can Cau Cont 9: 89-97, 1998 Colon Case-control Franceschi et al Int J Cancer 72:56-61, 1997 Lung Case-control Agudo et al Eur J Cancer 33: , 1997 Prostate 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 development 19 or 21 human epidemiological studies provide evidence of protection against cancer, especially rectal and stomach cancers (1 study reported increase) Concerns Growth 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
1.0 0.9 0.8 Relative Risk 0.3* 225 incident cases of prostate cancer in 12,395 California Seventh-Day Adventist men Frequent 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 performed Our 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 <1 1 >1 confidence interval Daily Intake (servings) Cancer Causes and Control 9: 553, 1998

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 Types of Bioactive Compounds May Vary with New Varieties
Tomato 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
p21+/+ AIN-76A Diet 100 p21+/- AIN-76A Diet 90 80 p21+/+ *Western Diet 70 p21-/- AIN-76A Diet 60 p21+/- Western Diet Percent survival 50 40 p21-/- *Western Diet Elimination 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. 30 20 10 *(high fat and phosphate, low calcium and vitamin D) 4 8 12 16 20 24 28 32 36 Weeks Yang et al, Cancer Res. 61, 565, 2001

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 Women’s Health Study
7 years of follow up found no association in 15,000 cancers in women and 33,000 cancers cases in men Women’s 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 Nurse’s 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"


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 Selenium Vitamin E Placebo 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


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 For more information on this study, go online to: 34

35 ECOG Trials Included in Analysis
Population Node positive High-risk node negative ER positive Premenopausal ER negative PgR negative Chemotherapy Cyclophosphamide, doxorubicin, taxane Cyclophosphamide, doxorubicin, fluorouracil Cyclophosphamide, doxorubicin, fluorouracil vs wk regimen Endocrine therapy Tamoxifen ± aromatase inhibitor None vs goserelin vs goserelin + tamoxifen None Patients with BMI data, n 3484 1502 613 For more information on this study, go online to: 35

36 Obesity and Outcomes in Subgroup Analysis of E1199
E Subgroup DFS OS HR (95% CI) P Value ER and/or PgR positive, HER2 negative 1.23 ( ) .035 1.46 ( ) .002 ER, PgR, HER2 negative (n = 708) 1.01 ( ) .93 1.05 ( ) .75 HER2 positive (n = 661) 1.07 ( ) .70 0.89 ( ) .55 For 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
DFS OS HR (95% CI) P Value E5188 (ER/PgR positive, HER2 negative) 1.41 ( ) < .0001 1.51 ( ) E3189 (ER negative) 0.90 ( ) .41 0.83 ( ) .18 For more information on this study, go online to: Sparano J, et al. SABCS Abstract S2-1. 37

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 Antioxidant reduces efficacy of cisplatin
Vitamin E Inhibits Cisplatin-Induced Apoptosis in MCF-7 Breast Cancer Cells. 6 - Antioxidant reduces efficacy of cisplatin 4 - % Apoptosis + ** 2 - * 0 - Control E CP CP+E Salganik, 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 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 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 meats If 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?
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

44 What Counts as a Serving?
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 Meats 2–3 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 life’s 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)
Crushed tea leaves Polyphenol oxidase Oxidation, Polymerization Dried Tea Leaves O OR 2 HO OH R 1 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 Yang CS. Personal Communication

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

58 Influence of Caffeine on Bone Mass May Depend on Genes
6 < 300 mg Caffeine > 300 mg D Spine Bone Mass Density (%) -6 BACKGROUND: 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. -12 TT Tt tt TT Tt tt Vitamin D Receptor Genotype Rapuri 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, 1994 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 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: 21172 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 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 subjects Se (200 mg) as Brewers Yeast vs. Placebo, follow-up 6.4 yrs Selenium Placebo RR 97% CI Skin Cancer Squamous cell Basal cell Cancer (- Skin) Lung Prostate Colorectal Breast All Sites (- Skin) Clark et al. JAMA 276: 1957, 1996.

62 Effects of Microwave Heating of Garlic on Total DMBA-Induced DNA Adducts
1000 30 seconds a 60 seconds a 750 (nmol Adducts/mol DNA) DNA Adducts 500 b b 250 Peel/ Crushed Control Microwave/ Peel/ Crushed Song and Milner J Nutr 1999;129:657-61

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

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