Academy Comments to NIH re Cancer Moonshot Initiative

July 1, 2016

Blue Ribbon Panel
National Cancer Moonshot Initiative
National Cancer Institute
9609 Medical Center Drive
Bethesda, MD 20892-9760

Dear Sir or Madam,

The Academy of Nutrition and Dietetics (the "Academy") appreciates the opportunity to submit these comments to the Blue Ribbon Panel of the National Cancer Institute (NCI) related to its May 13, 2016 request for information regarding the National Cancer Moonshot Initiative. Representing more than 100,000 registered dietitian nutritionists (RDNs),1 nutrition and dietetic technicians, registered (NDTRs), and advanced-degree nutritionists, the Academy is the largest association of food and nutrition professionals in the United States and is committed to improving the nation's health through food and nutrition across the lifecycle. Every day we work with Americans in all walks of life — from prenatal care through end of life care — providing nutrition care services and conducting nutrition research.

The Academy agrees with the aim of the initiative to improve our ability to prevent cancer and make more therapies—particularly clinically and cost effective medical nutrition therapies—available to more patients. It is the position of the Academy of Nutrition and Dietetics that primary prevention is the most effective and affordable method to prevent chronic disease, and that dietary intervention positively impacts health outcomes across the life span. Registered dietitian nutritionists and nutrition and dietetic technicians, registered are critical members of health care teams and are essential to delivering nutrition-focused preventive services in clinical and community settings, advocating for policy and programmatic initiatives, and leading research in disease prevention and health promotion.2

A. Nexus between Nutrition and Cancers

3

As the Academy noted in its formal request4 to the Centers for Medicare and Medicaid Services (CMS) for a National Coverage Determination expanding coverage of medical nutrition therapy:

Cancer is primarily an environmental disease, though genetics influence the risks of some cancers. Common environmental factors leading to cancer include, but are not limited to, poor diet and obesity, lack of physical activity and environmental pollutants.5 Evidence suggests that about 20% of the 1.685 million new cancer diagnoses (or 337,000 cases) expected in 2016 will be related to overweight or obesity, physical activity, and poor nutrition (including alcohol abuse) and thus could be prevented. In fact, following healthy lifestyle guidelines reduces incidence and mortality by 36% and 40%, respectively. Overweight and obesity are associated with increased risk of developing many cancers, including cancers of the breast in postmenopausal women, colorectum, endometrium, kidney, liver, pancreas and esophagus. There is also increasing evidence that obesity and overweight increases the risk for cancer recurrence and decreases the likelihood of survival for many cancers.6,7

Cancer incidence rates have decreased for both men and women across all racial and ethnic groups except for American Indian/Alaska Native women, where rates were stable from 2000 to 2010.8 Although death rates from cancer have also decreased, cancer claims more lives than heart disease among individuals younger than 85 years of age.9 Excessive adiposity, poor dietary patterns, and physical inactivity are risk factors that contribute to incidence of several common cancers: colon, breast, uterine, esophageal, and renal cancers.10 Obesity and/or overweight is implicated in 14% of cancer deaths in men and 20% of cancer deaths in women.11 Alcohol intake at rates beyond that considered moderate has been shown to increase the risk of several cancers, including mouth, esophagus, pharynx, larynx, liver, and breast. Dietary interventions have shown promise for primary prevention of some types of cancer.12,13 Physical activity also plays an important role in cancer prevention.14 Dietary modifications to reduce fat intake demonstrate effectiveness at reducing the risk of cancer of the breast15 and ovary.16 Regular moderate to vigorous physical activity results in a 30% reduction of colon cancer risk.17 RDNs are uniquely positioned to provide the education and counseling needed to effect the desired behavioral changes.

The Academy urges the Cancer Moonshot Initiative to strongly focus on modifiable lifestyle behaviors, such as diet and physical activity, both to prevent cancer as well improve health outcomes (e.g., reducing risk of recurrence, second primaries, slowing progression, and even all-cause mortality) for those diagnosed with cancer.

B. Nutrition as Cancer Prevention

In looking at cancer prevention, the Cancer Moonshot Initiative, as federal health policy, should turn to the 2015 Dietary Guidelines for Americans (DGA or the "Dietary Guidelines"), because the DGA are statutorily required to be used "in developing Federal food, nutrition, and health policies and programs."18 The 2015 DGA found that "[m]oderate evidence indicates that healthy eating patterns also are associated with a reduced risk of type 2 diabetes, certain types of cancers (such as colorectal and postmenopausal breast cancers), overweight, and obesity." In addition, the 2015 DGA recognized that "research has shown that vegetables and fruits are associated with a reduced risk of many chronic diseases, including CVD, and may be protective against certain types of cancers."19 An emphasis on plant foods, especially fruits, vegetables, whole grains and legumes, would substantially reduce risk, but most Americans would need to substantially shift their dietary habits to meet these guidelines.

1. Prevention Recommendations

Americans have a distinct lack of knowledge and understanding of the nexus between nutrition, weight, obesity, and cancer, particularly among our youth. Prevention can be supported through both individual and community based foci on weight management and physical activity that can be provided by RDNs and interdisciplinary team members. These efforts should ideally be done in partnership with other cancer outreach and treatment organizations, such as American College of Surgeons, American Society of Clinical Oncology, and the American Cancer Society. Although all of these organizations are initiating programs, combined efforts working with government entities would be more influential. For this outreach to happen, however, there must be funding and coverage for primary and secondary prevention that is presently woefully inadequate.

Relatedly, there must be a better understanding among all health care professionals about the role of one's diet in cancer risk. Whether including nutrition to a greater extent in the curriculum or incorporating it into continuing education, ensuring health care practitioners are sufficiently knowledgeable in this area is fundamental to cancer prevention.

It would be a mistake for the Cancer Moonshot Initiative not to examine broad, holistic, and non-medical solutions for actually preventing cancer. The Academy encourages the federal government to review its various food and nutrition policies to see whether their impacts are consistent with the recommendations in the DGA. In short, the federal government should direct its resources to make sure the healthy choice is the easy choice for consumers. What can be done to improve our food system to encourage production and consumption of high quality, nutrient dense foods, and what can be done to stop directly or indirectly subsidizing foods with low nutrient quality?

2. Role of a Plant-Based Diet in Cancer Prevention

20

Vegetarians tend to have an overall cancer rate lower than that of the general population, and this is not confined to smoking-related cancers. Data from the Adventist Health Study revealed that nonvegetarians had a substantially increased risk for both colorectal and prostate cancer compared with vegetarians, but there were no significant differences in risk of lung, breast, uterine, or stomach cancer between the groups after controlling for age, sex, and smoking.21 Obesity is a significant factor increasing the risk of cancer at a number of sites.22 Because the BMI of vegetarians tends to be lower than that of nonvegetarians, the lighter body weight of the vegetarians may be an important factor.

A vegetarian diet provides a variety of cancer-protective dietary factors.23 Epidemiologic studies have consistently shown that a regular consumption of fruit and vegetables is strongly associated with a reduced risk of some cancers.24,25,26 In contrast, among survivors of early stage breast cancer in the Women's Healthy Eating and Living trial, the adoption of a diet enhanced by additional daily fruit and vegetable servings did not reduce additional breast cancer events or mortality over a 7-year period.27 Fruit and vegetables contain a complex mixture of phytochemicals, possessing potent antioxidant, antiproliferative, and cancer-protective activity.

The phytochemicals can display additive and synergistic effects, and are best consumed in whole foods. These phytochemicals interfere with several cellular processes involved in the progression of cancer.28,29,30 These mechanisms include the inhibition of cell proliferation, inhibition of DNA adduct formation, inhibition of phase 1 enzymes, inhibition of signal transduction pathways and oncogene expression, induction of cell cycle arrest and apoptosis, induction of phase 2 enzymes, blocking the activation of nuclear factor-kappaB, and inhibiting angiogenesis.31

According to the recent World Cancer Research Fund report,32 fruit and vegetables are protective against cancer of the lung, mouth, esophagus, and stomach, and to a lesser degree some other sites. The regular use of legumes also provides a measure of protection against stomach and prostate cancer.33 Fiber, vitamin C, carotenoids, flavonoids, and other phytochemicals in the diet are reported to exhibit protection against various cancers. Allium vegetables may protect against stomach cancer and garlic protects against colorectal cancer. Fruits rich in the red pigment lycopene are reported to protect against prostate cancer.34 Recently, cohort studies have suggested that a high intake of whole grains provided substantial protection against various cancers.35 Regular physical activity provides significant protection against most of the major cancers.36 Although there are a variety of potent phytochemicals in fruit and vegetables, human population studies have not shown large differences in cancer incidence or mortality rates between vegetarians and nonvegetarians.37,38 Perhaps more detailed food consumption data are needed because the bioavailability and potency of phytochemicals depends on food preparation, such as whether the vegetables are cooked or raw. In the case of prostate cancer, a high dairy intake may lessen the chemoprotective effect of a vegetarian diet. Use of dairy and other calcium-rich foods have been associated with an increased risk of prostate cancer,39,40,41 although not all studies support this finding.42

Red meat and processed meat consumption is consistently associated with an increase in the risk of colorectal cancer (143).43 On the other hand, the intake of legumes was negatively associated with risk of colon cancer in nonvegetarians (98).44 In a pooled analysis of 14 cohort studies, the adjusted risk of colon cancer was substantially reduced by a high intake of fruit and vegetable vs a low intake. Fruit and vegetable intakes were associated with a lower risk of distal colon cancer, but not with proximal colon cancer (156).45 Vegetarians have a substantially greater intake of fiber than nonvegetarians. A high fiber intake is thought to protect against colon cancer, although not all research supports this. The EPIC study involving 10 European countries reported a 25% reduction in risk of colorectal cancer in the highest quartile of dietary fiber intake compared to the lowest. Based upon these findings, Bingham and colleagues (157)46 concluded that in populations with a low fiber intake, doubling the fiber intake could reduce the colorectal cancer by 40%. On the other hand, a pooled analysis of 13 prospective cohort studies reported a high dietary fiber intake was not associated with a decreased risk of colorectal cancer after accounting for multiple risk factors (158).47

Soy isoflavones and soy foods have been shown to possess anti-cancer properties. A meta-analysis of eight studies (one cohort, and seven case control) conducted in high-soy-consuming Asians showed a significant trend of decreasing risk of breast cancer with increasing soy food intake. In contrast, soy intake was unrelated to breast cancer risk in studies conducted in 11 low-soy-consuming Western populations (159).48 However, controversy remains regarding the value of soy as a cancer-protective agent, because not all research supports the protective value of soy towards breast cancer (160).49 On the other hand, meat consumption has been linked in some, but not all, studies with an increased risk of breast cancer (161).50 In one study, breast cancer risk increased by 50% to 60% for each additional 100 g/day of meat consumed (162).51

C. Nutrition-Based Interventions Are Effective in Treating Cancer

52

An expert panel convened by the American Cancer Society ("ACS") recognized the importance of optimal nutrition for cancer patients in all stages of disease and treatment. The experts were from various fields, including nutrition, physical activity, and cancer and were asked to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer, during the phases of cancer treatment and recovery, living after recovery from treatment, and living with advanced cancer. Survivors in each of these phases have different needs and challenges with respect to nutrition and physical activity, influenced by both the characteristics of the cancer and therapeutic methods.53

In conjunction with ACS, the Oncology Nursing Society has developed evidence-based interventions to prevent and manage anorexia in cancer patients; they recommended MNT as an effective treatment.54 MNT by a RDN has proven to result in positive health outcomes. A grade I conclusion statement from a systematic review by the Evidence Analysis Library55 indicates that MNT provided by an RDN was effective in improving multiple treatment outcomes.56

Eleven studies evaluated the effectiveness of nutrition intervention provided by an RDN to patients receiving radiotherapy or combined radiotherapy for a variety of high-nutrition risk cancers (e.g., head and neck and gastrointestinal cancers). Outcomes positively impacted by nutrition intervention include:

  • Calorie and protein intake;57
  • Dietary behaviors in breast cancer patients;58
  • Anthropometric measurements, including weight;59,60
  • Body composition measurements, including preservation of fat-free mass;61
  • Patient satisfaction, both with nutrition services provided and with overall care provided;62
  • Degree of deterioration in nutritional status, including wasting;63
  • Quality of life (QoL):
    • Decrease in QoL during treatment;64,65
    • Recovery time after treatment;66
  • Symptom
    • Fatigue, pain, nausea/vomiting;67
    • Sleep disturbance;68 and
    • Appetite.69
  • Radiotherapy-induced toxicities;70
  • Physical function;71
  • Number of unplanned hospital admissions;72
  • Length of hospital stay;73 and
  • Improved tolerance of planned treatment.74

The unfortunate, fundamental problem is that cancer patients will never receive these effective medical nutrition therapy services unless there is dedicated coverage or payment models that enable employment of the RDNs qualified to provide them. There is an urgent need to provide better, more thorough evidence-based nutrition and physical activity interventions for our pediatric and adult cancer survivors to prevent recurrence in this high risk population. With revised payment models and stronger recommendations for these interventions as mandatory elements of the standard of care, we can improve health and ameliorate their infrequent and inconsistent application resulting from the lack of RDNs in the clinical setting.

In addition to marked improvements in health outcomes, MNT also reduces costs related to the incidence and treatment of cancer in adults. One positive-quality cost-effectiveness study (class M) in the United States, Bos et al, (2011) assessed how cost-effective the Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHI-DM) would be if implemented as a public health intervention. The WHI-DM studied the effects of a low-fat dietary pattern on the prevention of cancer in 48,835 postmenopausal women, aged 50 - 79 years, without prior cancer and consuming >32% of their energy from fat. Cost-effectiveness was estimated through QALYs and the main outcome measure was the incremental cost-effectiveness ratio (ICER). From the societal perspective, the ICERs for the 50-year old cohort are $13,773 per QALY (95% confidence interval: $7,482 to $20,916) for women consuming >36.8% of energy from fat at baseline and $10,544 per QALY (95% confidence interval: $2,096 to $23,673) for women at high risk for breast cancer. From a private healthcare payer perspective, the ICER is $66,059 per QALY (95% confidence interval: $30,155 to $121,087) and from a Medicare perspective, the ICER is $15,051 per QALY (95% confidence interval: $6,565 to $25,105). The authors concluded that the WHI-DM is a cost-effective strategy for the prevention of breast and ovarian cancer from both societal and Medicare perspectives.75

D. Research

The Academy's Oncology Nutrition Dietetic Practice Group offers a number of suggested research topics and areas of focus related to diet, nutrition, and cancer:

  • Further research involving outcomes and decreased readmissions with medical nutrition therapy in the head and neck and esophageal cancer populations;
  • Public, proactive research on the role of chemicals in our world and cancer given their ubiquity and a lack of knowledge about their long term impacts on the body;
  • Funding for non-pharmaceutical clinical trials on (1) quality of life issues, such as reducing acute and chronic side effects; (2) whether vitamin supplementation helps or hinders during chemo and/or radiation therapy; (3) whether glutamine helps with reducing side effects; and additional research into the impact of prophylactic hydration for kidney protection;
  • Identifying differences in outcomes when RDNs provide interventions as a mandatory component of treatment as opposed to when they do not;
  • Encouraging all clinical trials to be designed to collect basic nutrition data and record any nutrition-related interventions the patient receives. Given that the presence of malnutrition is strongly associated with poorer outcomes in cancer patients, RDNs would be invaluable during clinical trial design and execution to ensure nutrition data are collected and interventions delivered;
  • Collection of basic data on nutrition status and outcomes with new immunologically-based therapies;
  • Given that the long-term consequences of malnutrition in the pediatric oncology population are even more severe in children as compared with adults, research is needed identifying how to best manage the nutrition status of children in cancer treatment, as well as nutritional interventions to reduce the intensity and frequency of late health effects. This includes research on how improved nutrition interventions during and after cancer treatment can address serious health consequences such as heart disease, loss of fertility, diabetes, obesity, cognitive deficits, and more;
  • Despite the focus on the genetic underpinnings of cancer and disease cure, there is a lack of sufficient research on critical gene-nutrition interactions, including impacts on epigenetics before, during, and after cancer development. Cancer development is a multistep, multistage process, often taking place over the course of years and decades (adults), and the importance of nutrition in this process is poorly understand; and
  • Although bench science confirms that nutritional factors may impact tumor evolution and progression, further research in animal models and humans is necessary to put more of these early findings into real world settings to maximize the curative potential of existing cancer therapies.

E. Conclusion

The Academy sincerely appreciates the opportunity to offer comments on the Cancer Moonshot Initiative, and we would welcome the opportunity to assist the Blue Ribbon Panel or NCI going forward. Please contact either Jeanne Blankenship by telephone at 312-899-1730 or by email at jblankenship@eatright.org or Pepin Tuma by telephone at 202-775-8277 ext. 6001 or by email at ptuma@eatright.org with any questions or requests for additional information.

Sincerely,

Jeanne Blankenship, MS, RDN
Vice President
Policy Initiatives and Advocacy
Academy of Nutrition and Dietetics

Pepin Andrew Tuma, Esq.
Senior Director
Government & Regulatory Affairs
Academy of Nutrition and Dietetics


1 The Academy recently approved the optional use of the credential "registered dietitian nutritionist (RDN)" by "registered dietitians (RDs)" to more accurately convey who they are and what they do as the nation's food and nutrition experts. The RD and RDN credentials have identical meanings and legal trademark definitions.

2 Position of the Academy of Nutrition and Dietetics: The Role of Nutrition in Health Promotion and Chronic Disease Prevention. J Acad Nutr Diet. 2013;113:972-979.

3 Ibid.

4 Gradwell E, Raman PR. The Academy of Nutrition and Dietetics National Coverage Determination formal request. J Acad Nutr Diet. 2012;112(1):149-76.

5 Anand P, Kunnumakkara AB, Kunnumakara AB, et al. (September 2008). "Cancer is a preventable disease that requires major lifestyle changes". Pharm. Res. 25 (9): 2097–116

6 Cancer Facts & Figures, 2016, American Cancer Society. Available at http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2016/.  Accessed June 30, 2016.

7 Mudryj AN1, Yu N, Aukema HM. Nutritional and health benefits of pulses. Physiologie appliquée, nutrition et métabolisme. Appl Physiol Nutr Metab. 2014 Nov;39(11):1197-204.

8 Jemal A, Siegal R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5): 277-300.

9 Ibid.

10 National Cancer Institute. Cancer trends progress report—2011/2012 Update. http://progressreport.cancer.gov/. Accessed October 15, 2012.

11 Ibid.

12 National Cancer Institute. Cancer trends progress report—2011/2012 Update. http://progressreport.cancer.gov/. Accessed October 15, 2012.

13 Prentice RL, Thomson CA, Caan B, et al. Low-fat dietary pattern and cancer incidence in the women's health initiative dietary modification randomized controlled trial. J Natl Cancer Inst. 2007;99(20):1534-1543.

14 Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer. JAMA. 2006;295(6):629-642.

15 National Cancer Institute. Cancer trends progress report—2011/2012 Update. http://progressreport.cancer.gov/. Accessed June 30, 2015.

16 Prentice RL, Thomson CA, Caan B, et al. Low-fat dietary pattern and cancer incidence in the women's health initiative dietary modification randomized controlled trial. J Natl Cancer Inst. 2007;99(20):1534-1543.

17 National Cancer Institute. Cancer trends progress report—2011/2012 Update. http://progressreport.cancer.gov/.  Accessed June 30, 2015.

18 U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines/.

19 Ibid.

20 From the Position of the Academy of Nutrition and Dietetics: Vegetarian Diets. J Am Diet Assoc. 2009;109: 1266-1282.

21 Fraser GE. Associations between diet and cancer, ischemic heart disease, and allcause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr. 1999;70(suppl):532S-538S.

22 World Cancer Research Fund. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 2007.

23 Dewell A, Weidner G, Sumner MD, Chi CS, Ornish D. A very-low-fat vegan diet increases intake of protective dietary factors and decreases intake of pathogenic dietary factors. J Am Diet Assoc. 2008;108:347-356.

24 Liu RH. Health benefits of fruits and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003;78(suppl):517S-520S.

25 Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: Progress and promise. Antioxid Redox Signal. 2008;10:475-510.

26 Béliveau R, Gingras D. Role of nutrition in preventing cancer. Can Fam Physician. 2007;53:1905-1911.

27 Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealey S, Al-Delaimy WK, Bardwell WA, Carlson RW, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Madlensky L, Marshall J, Newman VA, Ritenbaugh C, Thomson CA, Wasserman L, Stefanick ML. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: The Women's Healthy Eating and living (WHEL) randomized trial. JAMA. 2007;298:289-298.

28 Lila MA. From beans to berries and beyond: Teamwork between plant chemicals for protection of optimal human health. Ann N Y Acad Sci. 2007;1114:372-380.

29 Liu RH. Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J Nutr. 2004;134(suppl):3479S-3485S.

30 Wallig MA, Heinz-Taheny KM, Epps DL, Gossman T. Synergy among phytochemicals within crucifers: Does it translate into chemoprotection? J Nutr. 2005;135(suppl): 2972S-2977S.

31 Liu RH. Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J Nutr. 2004;134(suppl):3479S-3485S.

32 World Cancer Research Fund. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 2007.

33 Ibid.

34 Ibid.

35 Jacobs DR, Marquart L, Slavin J, Kushi LH. Whole-grain intake and cancer: An expanded review and meta-analysis. Nutr Cancer. 1998;30:85-96.

36 World Cancer Research Fund. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 2007.

37 Key TJ, Fraser GE, Thorogood M, Appleby PN, Beral V, Reeves G, Burr ML, Chang-Claude J, Frentzel-Beyme R, Kuzma JW, Mann J, McPherson K. Mortality in vegetarians and nonvegetarians: Detailed findings from a collaborative analysis of 5 prospective studies. Am J Clin Nutr. 1999;70(suppl):516S-524S.

38 Key TJ, Appleby PN, Rosell MS. Health effects of vegetarian and vegan diets. Proc Nutr Soc. 2006;65:35-41.

39 World Cancer Research Fund. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 2007.

40 Allen NE, Key T, Appleby PN, Travis RC, Roddam AW, Tjønneland A, Johnsen NF, Overvad K, Linseisen J, Rohrmann S, Boeing H, Pischon T, Bueno-de-Mesquita HB, Kiemeney L, Tagliabue G, Palli D, Vineis P, Tumino R, Trichopoulou A, Kassapa C, Trichopoulos D, Ardanaz E, Larrañaga N, Tormo MJ, González CA, Quirós JR, Sánchez MJ, Bingham S, Khaw KT, Manjer J, Berglund G, Stattin P, Hallmans G, Slimani N, Ferrari P, Rinaldi S, Riboli E. Animal foods, protein, calcium and prostate cancer risk: The European Prospective Investigation into Cancer and Nutrition.  Br J Cancer. 2008;98:1574-1581.

41 Chan JM, Stampfer MJ, Ma J, Gann PH, Garziano JM, Giovannucci EL. Dairy products, calcium, and prostate cancer risk in the Physician's Health Study. Am J Clin Nutr. 2001;74:549-554.

42 Tavani A, Gallus S, Franceschi S, La Vecchia C. Calcium, dairy products, and the risk of prostate cancer. Prostate. 2001;48: 118-121.

43 World Cancer Research Fund. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 2007.

44 Fraser GE. Associations between diet and cancer, ischemic heart disease, and all cause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr. 1999;70(suppl):532S-538S.

45 Koushik A, Hunter DJ, Spiegelman D, Beeson WL, van den Brandt PA, Buring JE, Calle EE, Cho E, Fraser GE, Freudenheim JL, Fuchs CS, Giovannucci EL, Goldbohm RA, Harnack L, Jacobs DR Jr, Kato I, Krogh V, Larsson SC, Leitzmann MF, Marshall JR, McCullough ML, Miller AB, Pietinen P, Rohan TE, Schatzkin A, Sieri S, Virtanen MJ, Wolk A, Zeleniuch-Jacquotte A, Zhang SM, Smith-Warner SA. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies. J Natl Cancer Inst.  2007;99:1471-1483.

46 Bingham SA, Day NE, Luben R, Ferrari P, Slimani N, Norat T, Clavel-Chapelon F, Kesse E, Nieters A, Boeing H, Tjønneland A, Overvad K, Martinez C, Dorronsoro M, Gonzalez CA, Key TJ, Trichopoulou A, Naska A, Vineis P, Tumino R, Krogh V, Bueno-de-Mesquita HB, Peeters PH, Berglund G, Hallmans G, Lund E, Skeie G, Kaaks R, Riboli E; European Prospective  Investigation into Cancer and Nutrition.  Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): An observational study. Lancet. 2003;361:1496-1501.

47 Park Y, Hunter DJ, Spiegelman D, Bergkvist L, Berrino F, van den Brandt PA, Buring JE, Colditz GA, Freudenheim JL, Fuchs CS, Giovannucci E, Goldbohm RA, Graham S, Harnack L, Hartman AM, Jacobs DR Jr, Kato I, Krogh V, Leitzmann MF, McCullough ML, Miller AB, Pietinen P, Rohan TE, Schatzkin A, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Zhang SM, Smith-Warner SA. Dietary fiber intake and risk of colorectal cancer. A pooled analysis of prospective cohort studies. JAMA. 2005; 294:2849-2857.

48 Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008;98:9-14. 

49 Messina MJ, Loprinzi CL. Soy for breast cancer survivors: A critical review of the literature. J Nutr. 2001;131(suppl):3095S-3108S.

50 Missmer SA, Smith-Warner SA, Spiegelman D, Yaun SS, Adami HO, Beeson WL, van den Brandt PA, Fraser GE, Freudenheim JL, Goldbohm RA, Graham S, Kushi LH, Miller AB, Potter JD, Rohan TE, Speizer FE, Toniolo P, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hunter DJ. Meat and dairy food consumption and breast cancer: A pooled analysis of cohort studies. Int J Epidemiol. 2002;31:78-85.

51 Bessaoud F, Daurès JP, Gerber M. Dietary factors and breast cancer risk: A case control study among a population in Southern France. Nutr Cancer. 2008;60:177-187.

52 Gradwell E, Raman PR. The Academy of Nutrition and Dietetics National Coverage Determination formal request. J Acad Nutr Diet. 2012;112(1):149-76.

53 Doyle C, Kushi LH, Byers T, Courneya KS, Demark-Wahnefried W, Grant B, McTiernan A, Rock CL, Thompson C, Gansler T, Andrews KS, 2006 Nutrition, Physical Activity and Cancer Survivorship Advisory Committee:  American Cancer Society.  Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices.  CA Cancer J Clin 2006;56(6):323-53.

54 Adams LA, Shepard N, Caruso RA, Norling MJ, Belansky H, Cunningham RS. Putting evidence into practice: evidence-based interventions to prevent and manage anorexia. Clin J Oncol Nurs 2009 Feb;13(1):95-102.

55 The Evidence Analysis Library (EAL) is a synthesis of the best, most relevant nutritional research on important dietetic practice questions housed within an accessible, online, user-friendly website.  An objective and transparent methodology is used to assess food and nutrition-related science. The EAL is a series of systematic reviews developed by Academy members for Academy members based on a predefined approach and criteria.  Meticulous methods and electronic tools are used to document each step to ensure objectivity, transparency and reproducibility of the process.  Expert workgroup members evaluate, synthesize, and grade the strength of the evidence to support conclusions that answer a precise series of questions.

56 Academy of Nutrition and Dietetics Evidence Analysis Library "Is medical nutrition therapy (MNT) provided by a nutrition professional effective in adult oncology patients receiving radiation treatment?" Accessed June 20, 2016:http://www.andeal.org/topic.cfm?cat=4832&conclusion_statement_id=251675.

57 Goncalves Dias MC, de Fatima Nunes Marucci, Nadalin W, Waitberg DL. (2005). Nutritional intervention improves the caloric and protein ingestion of head and neck cancer patients under radiotherapy. Nutr. Hosp. 20:320-325.

58 Chlebowski RT, Blackburn GL, Buzzard IM, Rose DP, Martino S, Khandekar JD, York RM, Jeffery RW, Elashoff RM, Wynder EL. Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.J Clin Oncol. 1993 Nov; 11 (11): 2,072-2,080.

59 Goncalves Dias MC, de Fatima Nunes Marucci, Nadalin W, Waitberg DL. (2005). Nutritional intervention improves the caloric and protein ingestion of head and neck cancer patients under radiotherapy. Nutr. Hosp.20:320-325.

60 Isenring E, Capra S, Bauer J. Patient satisfaction is rated higher by radiation oncology outpatients receiving nutrition intervention compared with usual care.J Hum Nutr Diet. 2004; 17: 145-152.

61 Ibid.

62 Ibid.

63 Isenring EA, Bauer JD, Capra S. Nutrition Support Using the American Dietetic Association Medical Nutrition Therapy Protocol for Radiation Oncology Patients Improves Dietary Intake Compared with Standard Practice.J Am Diet Assoc 2007; 107 (3): 404-412.

64 Isenring E, Capra S, Bauer J. Patient satisfaction is rated higher by radiation oncology outpatients receiving nutrition intervention compared with usual care.J Hum Nutr Diet. 2004; 17: 145-152.

65 Ravasco P, Monteiro-Grillo I, Vidal P, Camilo M.Dietary counseling improves patient outcomes: A prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy.J Clin Oncology.2005; 23: 1,431-1,438.

66 Isenring EA, Capra S, Bauer JD. Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and neck area. Br J Cancer. 2004;91(3):447-52.

67 Ravasco P, Monteiro-Grillo I, Vidal P, Camilo M.Dietary counseling improves patient outcomes: A prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy.J Clin Oncology.2005; 23: 1,431-1,438.

68 Ibid.

69 Ibid.

70 Ibid.

71 Isenring E, Capra S, Bauer J. Patient satisfaction is rated higher by radiation oncology outpatients receiving nutrition intervention compared with usual care.J Hum Nutr Diet. 2004; 17: 145-152.

72 Odelli C, Burgess D, Bateman L, Hughes A, Ackland S, Gillies J, Collins CE. Nutrition support improves patient outcomes, treatment tolerance and admission characteristics in esophageal cancer. Clinical Oncology. 2005;17:639-645.

73 Ibid.

74 Ibid.

75 Bos AM, Howard BV, Beresford SAA, Urban N, Tinker LF, Waters H, Bos AJ, Chlebowski R, Ennis JM.  Cost-effectiveness analysis of a low-fat diet in the prevention of breast and ovarian cancer. J Am Diet Assoc 2011;111:56-66.
10a Kolata, G. "A Long View on Health Care: Think Like an Investor"  New York Times, 2012 May 21.  http://www.nytimes.com/2012/05/22/health/views/a-long-view-on-health-care-think-like-an-investor.html
10b Goetzel, RZ. Do Prevention Or Treatment Services Save Money? The Wrong Debate. Health Aff January/February 2009 vol. 28  no. 1  37-41