Sponsored by the American Institute for Cancer Research and the World Cancer Research Fund International. July 11-12, 2002 Washington, D.C. Reported by Ann Fonfa “The exchange of ideas among cancer researches and health practitioners will bring us closer to understanding how the simple choices we make each day about food and exercise bolster or weaken the body’s defenses against cancer” Marilyn Gentry, President, AICR and WCRFI. Christine Friedenreich, PhD, Alberta Cancer Ctr. “Physical Activity and Cancer: Etiologic Evidence and Biological Mechanisms”, spoke about exercise as a means of prevention. She stated that a lifetime of physical activity could be very useful but that exercise can and should be done after diagnosis of cancer, during treatment as well. There is convincing evidence (20 studies worldwide) with consistent ‘associations’ showing dose-response (more is better). Some specific cancers were looked at. It is believed that the evidence that exercise reduces risk is ‘convincing’ for colon and breast cancer. ‘probable’ with prostate cancer. possible for endometrial and lung All other cancers have insufficient evidence (possibly based on very few, if any studies). Recommendations: 30 minutes of moderate to vigorous intensity activity per day, 5 days a week or more. She also mentioned that exercise might improve antioxidant defenses. David Klurfeld, PhD , Wayne State University “Calorie Restriction and Cancer” spoke about the studies done on mice. He mentioned that this idea was first published in 1909 by C. Mooreschi whose paper was “Underfeeding mice slows growth of transplanted tumors” . Ann’s NOTE: From other conferences and papers, I have heard that populations that were underfed as in some European countries during WWII, have reduced cancer risks observed. But this is a difficult ‘sell’ to a healthy population. Invar Bosaeus, MD, Sahlgrenska University Hospital “Dietary Intake, Resting Energy Expenditure, Weight Loss and Survival in Cancer Patients” spoke about cachexia. He mentioned that anti-inflammatory treatment was used. The afternoon sessions were split between A) Energy Balance and Cancer Risk or B) Phytochemicals/Phytoestrogens. Section B was chaired by Richard Rivlin, American Health Foundation (formerly Memorial Sloan Kettering). Tom J. Mabry, PhD and Delia Brownson, PhD split the topic “Anti-Cancer Natural Products: Anti-Viral Proteins and Flavinoids”. Dr. Mabry spent some time speaking about phytolacca or pokeweed which inactivates the rhybosomes and blocks protein synthesis in tumor cells. His laboratory is working on creating a drug. He discussed flavinoids which are “biosynthesized by every plant in nature”. Quercetin (found in onions and apples) can chelate metal ions. EPG (from tea or red wine) absorbs UV light Defuses free radicals Binds the estradiol receptor protein Resveratrol (from red wine) can prevent tumor development. He commented that raisins and grapes are good but the fermentation process makes it better. Dr. Mabry is involved with the Phytochemical Society of America. Ajit K. Verma, PhD, University of Wisconsin “Garlic Compounds in Cancer Prevention Treatment” started his talk by stating that there are over 100 compounds in garlic. Garlic has been shown to be effective in studies on animals and some human studies. It is not toxic and can be part of a daily diet. It contains lipid (fat)soluble components and water soluble ones. There have been epidemiological studies in Japan, Belgium, China, Australia, US, Netherlands for colon cancer. Greece, Switzerland, France, Netherlands for breast cancer. He felt that Allicyn was the main bio-active compound with 3.7 mg released enzymatically per gram of garlic. It can induce apoptosis (cell death-desirable), as shown in a prostate cell line. If there is a ras mutation present in the cancer cells, garlic can successfully affect this. Ann’s NOTE: I first met Dr. Rivlin (panel moderator) about five years ago at Memorial Sloan Kettering during a talk on garlic. At that time, I asked if whole garlic could be used as ‘medicine’. He agreed it could, but of course researchers are always looking for ‘the active’ element. I believe this is following a pharmaceutical model and may not in fact be the most useful method for cancer patients. The Project believes the synergistic and combination effect of many foods and natural substances will provide the most appropriate healing. Heide S. Cross, PhD, University of Vienna Medical School “Phytoestrogens Regulate Vitamin D Metabolism: Relevance for Colon and Prostate Tumor Prevention and Therapy”. She suggested that Vitamin D could provide an endogenous (internal) defense against tumors. She stated that Vitamin D, NSAIDS, calcium, retinoids (synthetic Vitamin A), isoflavones and antioxidants all act on one or more pathways of cancer progression. This has been shown in colon cancer. She then mentioned several studies using genistein (soy isoflavone) in mice. There was a significant increase in enzymes and various other good results. She also mentioned that getting 15 to 20 minutes a day of sunshine on one’s hands and face is considered cancer protective. Studies are also beginning to look at oral Vitamin D supplementation (100-200 IU). She mentioned that it is a steroid and care must be taken. Ann’s NOTE: I personally have been taking a gel cap of 400 IU Vitamin D for about the last 7-9 years. I also take my glasses off for about 30 seconds while in the sun. I read somewhere that it is good for one’s eyes to have indirect sun daily. A recent study suggested that African American women and children often did not get enough Vitamin D. This may be due to needing longer sun exposure to benefit or to diet. Dietary supplements might be an answer. Pirjo Pietinen, PhD, World Health Organization “Enterolactone and Risk of Cancer”. Dr. Pietinen discussed the ways to measure isoflavones, flavinoids, etc in many body fluids. Thus it is possible to determine what an individual’s dietary intake consists of. She mentioned the beneficial effects of a diet that includes seeds, nuts, legumes, vegetables, grains, berries and other fruits. She stated that animal data on the use of flaxseed shows a protective effect against tumors. (A member of the audience asked her if she was familiar with the several studies in humans showing a benefit from flaxseed intake-she was not). Ann’s NOTE: It is not uncommon for lay people to have a broader overview than a scientist. The researcher is often focused on the particular area they are ‘carving out’ with their studies. Allison Cesaere, Westchester Medical Center, “Connecting Underserved Populations with Phytochemical Rich Diets: A Menu for Program Design and Implementation”. She discussed the scope of the problem-health disparities, variability with little data and the (understandable) reluctance of the African-American community in particular, to participate in research. She pointed out that African-Americans consume significantly less fruits and vegetables and more meat than other populations. The use of protective supplements like folate or fiber is less. Yet 80% in a survey felt that nutrition was personally important. 36% were actively doing everything they could to achieve optimal nutrition. Complaints that most people have include: conflicting media messages-headlines often are misleading and confusing. difficulty giving up ‘enjoyable’ foods time factor in preparing food (a myth in Ann Fonfa’s opinion) In the Latino populations, they are not necessarily familiar with the U.S. fruits and vegetables. Children’s choices were found to be very influential. Recipes were needed in Spanish. Ann’s NOTE: There should be some instructions at the food markets about how to cut or prepare various fruits and vegetables. We all need assistance with this. Suggestions for cooking vegetables include steaming, stewing, roasting in the oven, grilling (no danger with grilling vegetables-except scrape off any charred areas), sauteeing-but use olive oil if possible. Some prior studies found that communities with low literacy prefer community-based discussion groups and demonstrations of food preparation. Ann’s NOTE: I raised the issue of the big bucks spent on advertising unhealthy snack foods and sodas in the school system, TV, magazines, billboards, etc. The National Cancer Institute’s program for “Five a Day” (five fruits/vegetables) is funded with $1 million. If Latino parents are listening to their kids, who probably speak some English, they may be getting the commercial messages more strongly. Some school systems are finally opting out of offering soda machines and ‘snack’ machines. The program described by this speaker was supported by Johnson & Wales University Culinary Institute which has programs on nutrition. Friday Morning Split Sessions were Diet, Colitis and the D) Etiology of Colon Cancer or C) Nutrition in Survivorship ( C) summarized below). Noreen Aziz, MD, PhD, MPH from the National Cancer Institute’s Office of Cancer Survivorship “Cancer Survivorship Research: Challenge and Opportunity”. There are 8.9 million cancer survivors in the USA today. This is mostly due to the success in treating childhood cancers. Although about 22% are breast cancer cases and 19% are prostate. Of course the largest number of survivors have gone at least 5 years but there are many who are over twenty years. Ann’s NOTE: There is some criticism of the five-year survivor unit as it is a somewhat arbitrary timing. It is least useful for breast and prostate which often come back. For breast cancer patients, almost half will die within 15 years of their disease. Dr. Aziz told the audience that her office was looking at the long-term, late and chronic effects of cancer treatment. She mentioned that this type of research is quite new. Long term effects are chronic and persistent. Late effects can occur months or years later. They can be system specific including organ failures, secondary cancers, premature aging, immuosuppression, endocrine dysfunction, pain syndrome and osteoporosis. There can be radiation-induced sarcomas and epithelial cancers. Chemotherapy can cause leukemia, bladder cancer and others. Ann’s NOTE: This site contains a lot of information about these effects. Take a look at Conventional Therapy in the Relevant Studies section. Also look at Articles that 'Critique'the System in this section (Meeting Summaries and Advocacy Issues). The phases of survivorship as described by Dr. Aziz include: Acute – diagnosis and completion of primary treatment. Extended – remission, watchful waiting following intermittent therapy (i.e. Tamoxifen). Permanent – extended disease-free survival, low likelihood of recurrence. The goals of research include: Identifying and examining prevention and control Identifying and exploring the tremendous health disparities among ethnic groups Creating follow-up care guidelines Exploring cancer communications between doctor and patient Examining the impact on the family and care-givers Economic impact of cancer There has been a shift away from the medical deficient/dysfunction model. An inter-disciplinary approach is needed. Research funds may be available from the Office of Cancer Survivorship. Cheryl Rock, PhD, RD, University of California at San Diego “Nutrition and Survival after the Diagnosis of Breast Cancer: Testing the Effects of Lifestyle Modification”. Dr. Rock suggested that with 203,500 new cases diagnosed in 2002, breast cancer accounted for 31% of incidence of cancers and 15% of the deaths. Can nutritional factors affect prognosis or the risk of recurrence? Studies in cell culture (in vitro) may be more relevant to post-treatment patients. There are very few guidelines, some small clinical trials with relevant studies do exist. Areas of focus: 1) relative body weight (or indicators of obesity), 40 studies done 2) diet composition (nutrients, energy, food ), 13 studies done Ann’s NOTE: As I write this, I am struck with the fact that 3X the number of studies explore obesity as compared to diet. Could part of this have to do with the fact that we can ‘medicalize’ obesity, but (so far) not diet? I am a strong believer that what one eats truly matters. But I do not encourage dieting per se. Most people who go on a diet are choosing short term things to quickly reduce weight. Every study shows that 95-98% of them will regain that weight and more. This is true with just about every program ever invented. However changing one’s eating plan forever by eating healthy foods (see our section on Food/Water/Product Issues for more), can offer better health benefits. Even if healthy eating does not prevent cancer or recurrences, and that is a big IF, it will be good for the heart and many other modern ailments. Dr. Rock noted that weight gain has not been proven to independently influence survival. A small study showed that lean mass decreased after chemotherapy, with a large gain in fat mass. And it is difficult to maintain physical activity during chemo. Ann’s NOTE: We suggest doing any small amount of exercise-walk around your bedroom if that is all you can do. Raise your arms up over your head every day. Do whatever you can, make sure you stand up, get out of bed every day if you can. Dr. Rock pointed out that in the studies that showed a benefit from intake of fruits and vegetables, there was a 20-90% reduction in risk of death. ¾ of the studies that looked at fiber showed a protective effect. Alcohol intake was not associated with survival in 8 studies (of survivors). One study found a non-significant association. The biological system of women after treatment is different. Dr. Rock described two of the largest current ongoing studies: WINS –using individual and group counseling sessions with one group of women to help them achieve lower fat intake. (all post-menopausal women). Ann’s NOTE: But there is no counseling about healthier fats and this is now acknowledged, even by the researchers involved, as being important. Study protocols cannot be changed after the study has begun without great difficulty. WHEL –looking at fruits, vegetables, fiber and lower fat. The idea is to see if survivors have a longer interval without developing recurrence (event-free interval). 2/3 of the women are under 55 with 57% at Stage II. 61% are ER positive. This study is using biomarker data, not food recall. They can measure plasma concentrations of nutrients. Women in the ‘treatment’ arm are hovering around a decent level of fruit, vegetable, fiber intake. The majority of women in the trial do NOT lose weight. The study ends in a few years and results are expected after 2005. Ann’s NOTE: It has recently been shown that many studies of use of fruits/vegetables for risk reduction have compared groups with almost no intake to those with minimum intake. W. Elaine Hardman, PhD, Pennington Biomedical Research Center "Omega-3 Fatty Acids to Augment Cancer Therapy". Dr. Hardman explained that Omega-3 fatty acids from fish oil have been shown to inhibit COX-2 induction. (at 10 grams per day for humans) Ann’s NOTE: Checking my supplement bottle for EPA/DHA, I note that one softgel provides 500 mgs of sardine oil. That would mean I would have to take 20 pills per day to get the 10 grams stated above. However, I also take 2 tablespoons of flaxoil in my food daily (measured in ml so not sure of equivalent), and take 3 gelcaps of Perilla Oil a source of Omega-3. I do occasionally eat fish –mostly wild salmon. I never eat farm-raised fish. I have been concerned about antibiotics and hormones which these fish could be fed. This speaker told us that farm-raised fish are fed corn oil which causes them to have higher levels of Omega-6 fatty acids than Omega-3. Not a good thing. Various studies have shown the value of fish oil in the human diet. Omega-3 has been shown to induce differentiation (Wang, 2000). This is to be desired for cancer patients. When a cell is malignant, it tends to lose its differentiation. It also depresses many inflammatory genes that can block apoptosis (that is cell death which is also desirable, we want cancer cells to die off). Omega-3 also decreases the estrogen metabolism (Noble et al, 1997;Osborn et al, 1988). It can suppress angiogenesis (development of blood vessels to a tumor) (Form & Auerbach, 1983). In a study important to patients in therapy, Bougnoux et al showed that the more Omega-3 in the tissues, the better the response to chemotherapy. Dr. Hardman stated that she sees no difference in fat from fish or supplements. In fact she suggested that the supplements might be purified in some ways. Tze-chen Hsieh, PhD, New York Medical College “Prevention and Management of Prostate Cancer Using Pc-Spes: a Clinical and Scientific Perspective". Dr. Hsieh gave an excellent talk outlining the scientific studies done on PC Spes as a combination of herbs and as individual ingredients. She deplored the fact that it was taken off the market due to possible contamination from wafarin and DES. The herbal mix was showing efficacy among men with prostate cancer who no longer responded to other hormonal therapies. Ann’s NOTE: Dr. Eric Small, speaking at an ASCO meeting on CAM suggested that the herbal formula may have natural elements that resemble these two drugs. However, indomethacin was also found and this may be true contamination. (For more information, you can go to Relevant Studies and find the section on Information by Cancer Types or see the report on ASCO 2002 under Meeting Summaries/Advocacy Issues). Charles A. Sklar, MD, Memorial Sloan Kettering "Late Effects in Survivors of Childhood Cancer: Opportunities for Intervention". Discussing pediatric survivorship, Dr. Sklar stated that they have achieved a 75% overall 5-year survival rate in all childhood cancers. In the year 2000, one in every 900 young adults was a survivor with 200,000 to 250,000 in North America. There are many late complications with 2/3 of those followed experiencing gastro-intestinal, cardio-pulmonary (heart/lungs), hearing or vision problems, endocrine/metabolism disruption and other dysfunctions. There are also second and subsequent malignancies, reduced bone mineral density/osteoporosis, obesity, and cardiovascular disease. The incidence of late complications continues to rise. The longer the follow-up, the more likely cardiac problems will develop. The median age of the survivors studied is mid 20’s. They have 6 times the illness of the general population. The biggest risk to these survivor’s health comes from treatment. External beam radiation, alkylating agents, topoisomerase II inhibitors, etc. Cranial irradiation:. This use of this method has been greatly reduced, especially as prophylaxis since it has been shown to cause neuro-endocrine problems, especially growth hormone deficiency. (J Med Pediatric Oncology). 40% of kids who received cranial radiation were had significant weight gains. Metabolic complications include hyperlipedemia and insulin resistance. In the short term, exposure to gluccorticoids affects dietary calcium. Most of the young girls will suffer loss of ovarian function and go into early menopause. In general, the younger the child, the more at risk for complications as they age. Females were found to be at greater risk than males. (Steinherz, JAMA). With Hodgkins Disease, there is a 3-9X greater risk of heart disease. They are 8 times more likely to die of heart disease (second only to new cancers). Ann’s NOTE: See our section on Children and Young Teens in the Conventional Therapy area in Relevant Studies for more information on children’s health and cancer. The final afternoon session was entitled ‘Population Epidemiology Intervention Studies’. The first speaker was Paolo Buffetta, MD, International Agency for Research on Cancer "Diet and Cancer in a Country in Transition: the Case of Uruguay". Uruguay has 2.3 million inhabitants with a temperate climate. It is located between Argentina and Southern Brazil. There is a very high cancer rate among men. The mortality rate is 203/100,000 in men compared to the U.S. 161.8/100,000. The rate for women is 121.1/100,000 compared to 116.4/100,000. There is almost twice as much breast cancer as prostate cancer and more ovarian cancer than in the United States. There is quite a lot of tobacco smoking, people use ‘black’ tobacco which has a higher risk of oral or pharyngeal cancer. There is also use of alcohol. The diet is composed of much salted and preserved/processed meats which can compose almost 28% of the diet. Both men and women drink mate, an herbal drink that is taken at very hot temperatures. Very little fruits and vegetables are eaten. The government of Uruguay has partnered with the International Agency for Research on Cancer in order to determine causes and control for their difficulties with cancer. Because it is a small country, it is believed that a national registry can gather very useful information, something like the Scandinavian countries. Heiner Boering, PhD, German Institute of Human Nutrition (DIfE), "Observational and Intervention Studies in the Area of Behavioral Changes". This speaker discussed the EPIC study- European Prospective Investigation into Cancer and Nutrition. This study has about 500,000 participants in 10 European countries (France, Denmark, Germany, Greece, Italy, Netherlands, Norway, Spain, Sweden and the United Kingdom). EPIC’s primary goal is to examine the relationship between diet and various lifestyle factors on the origins of cancer and other chronic diseases. It also aims to provide a scientific basis for public health recommendations. (THIS INFORMATION comes from the AICR ScienceNow 1, Summer 2002, newsletter). The EPIC trial will continue through 2020. Some preliminary findings have been reported: A high consumption of processed meats (like sausage and bacon) is linked to an increase in colon cancer risk. Fish consumption shows a significant reduction in colon cancer risk. Fruits and vegetables show a protective effect against cancers of the colon and rectum. In addition to the well-known effect of tobacco on lung cancer risk, alcohol and tobacco each demonstrate a strong correlation to cancers of the mouth, pharynx, larynx and esophagus. A combination of alcohol and tobacco indicates a multiplier effect that will increase the risk of a smoker-drinker 50 times over a nonsmoker-nondrinker. Daily consumption of five or more servings of fruits and vegetables can decrease by 50 percent the incidence of cancers of the mouth, pharynx, larynx and esophagus. Walter Willett, MD, Dr.PH, Harvard School of Health, "Diet and Cancer: An Evolving View". Dr. Willett is the main researcher involved with the Nurses’ Study II, 1991-1999. He began his talk by mentioning that the nature of milk has changed over the last 50 years. Cows are now pregnant about 50% of the time while producing milk. This is an unnatural situation. There is 3 times the progesterone in the milk of pregnant cows over non-pregnant. Dr. Willett suggested that fiber may be more beneficial for prevention of cardio-vascular disease than cancer. Folic acid appears to help protect against the risks that alcohol use increases. He then stated that there is no appreciable relationship between fruit/vegetables and breast or colon cancer. At less than 2 servings a day compared to 2 servings showed not benefit. According to Willett, the possible reasons for this include: possible bias in the case/control (comparison of the two groups), selective reporting/publication, fruits and vegetables might be too non-specific and there may be dilution of the effects due to supplementation and fortified foods. Ann’s NOTE: Another reason may be that neither group is eating anywhere near the recommended amount of fruits and vegetables (National Cancer Institute recommends a minimum of 5 servings per day). It was amazing to me that he did NOT mention this. Tim Byers, MD, MPH, University of Chicago "Future Directions in Integrative Strategies for Cancer Prevention". Dr. Byers discussed the limitations of all types of evidence. Randomized controlled trials can be limited by outcomes and short time frames. He also pointed out that various elements were important in different phases of life. Fetal (in utero), childhood and adolescence, and adulthood all have different implications for our later health. He mentioned that there were very few studies on prevention after cancer. He suggested that observational studies be extended to measure information after diagnosis. There is a keen interest in behavioral changes. He also suggested that nutritional randomized controlled trials be conducted. Ann’s NOTE: The Annie Appleseed Project has called for randomized clinical trials on nutrition and from the ‘patient’ perspective (we call it the Patient Track – see our front page bottom). Here are Dr. Byers 10 suggestions for improving the study of cancer (presented by him in ‘David Letterman’ style): 10) More critically examining newborns including autopsy studies of tissue 9) Better understanding correlates of weight 8) Design a new generation of ecological studies 7) Design a new generation of migrant studies 6) Use more retrospective recalls 5) Maintain mega-cohorts over time 4) Dust off historical cohorts - universities have them 3) More cross-generational record linkages 2) Study nutrition among cancer survivors, not just their ‘thing’ but as TREATMENT 1) Link cancer messages to some for other chronic diseases and interventions Ann’s NOTE: I strongly agree with these recommendations. Implementation of these could move our knowledge forward much more rapidly. AICR 2002 meeting abstract AICR 2002 meeting abstract Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. 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