A 5 year study by a team of 21 experts chaired by Sir Michael Marmot (Wikipedia) and sponsored by the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) has produced 500+ page report on diet, exercise and cancer, free to download at the Diet and Cancer Site ([report], [summary], [brochures]. Updates were released in 2010 (on breast cancer), 2011 (on colorectal cancer) and 2012 on pancreatic cancer. [updates]. It is expected that upcoming udpates will be available in 2013 on endometrial and ovarian cancers and on breast cancer survivors and in 2014 on cancers of prostate, bladder, kidney, liver and gallbladder. WCRF/AICR Timetable.
The report is in agreement with the last WCRF report published 10 years ago that "about one third of all cancers are preventable ... by appropriate food and nutrition, regular physical activity, and avoidance of obesity". (page xxv) In particular,
"cancer is a disease of genes, which are vulnerable to beneficial or harmful mutation, especially over the long human lifespan. Nutritional factors are important in determining the likelihood of some mutations, as well as in changing the functions of genes even without mutation. However, both epidemiological and experimental evidence shows that only a small proportion of cancers are inherited. Environmental factors are most important and can be modified. These include smoking and other use of tobacco; infectious agents; radiation; industrial chemicals and pollution; medication and also many aspects of food, nutrition, physical activity, and body composition. Essentially this is good news. It means that healthy environments can stop cancer before it starts. The evidence also indicates that such environments, including the factors that are the subject of this Report, may be able to check the cancer process after it has started. ... The most impressive initial evidence showing that patterns of cancer are altered by environmental factors, and are not mainly genetically determined, comes from studies describing changes in the rates of different cancers in genetically identical populations that migrate from their native countries to other countries. Such studies consistently show that changes in the rates of some of the most common cancers, including those of the stomach, colorectum, breast, and prostate, can be remarkable, even over one or two generations." (pages 2, 4)
The process followed to develop the report was to commission from scientific partners 20 independent systematic literature reviews (SLRs) using a common protocol (defined in a separate SLR Specification Manual) resulting in dose response curves (see Box 3.2 on page 52) and meta analyses displayed via forest plots (see Box 3.3 on page 53). The independence of the process was assured by separating the collection and assessement of the data and through the involvement of the peer reviewers. The process was developed by the Mechanisms Working Group headed by Dr. John Milner of the National Cancer Institute. Also see the business plan.
Judgments based on this work are displayed in matrices as well as an overview [Food Table]. The matrices and foldout categorize the strength of evidence in each case as convincing, probable, limited/suggestive, limited/no conclusion or unlikely to affect risk. Box 3.8 on page 60 and continued onto page 61 discusses the particular criteria that must be satisfied for each of these categories.
For prostate cancer their assessment of the evidence is given in the matrix on page 305 and discussed on pages 305-309 which we summarize here:
- probable evidence supporting a decreased risk of prostate cancer for food containing lycopene (forest plot and dose response curve p. 104)
- probable evidence supporting a decreased risk of prostate cancer for food containing selenium (forest plot and dose response curve p. 110). [Note that in 2008 the SELECT trial found that selenium does not reduce the risk of prostate cancer. See [link].]
- probable evidence supporting a decreased risk of prostate cancer for selenium (matrix p. 179) [This has been overturned by the SELECT trial as in note above.]
- limited/suggestive evidence that pulses (i.e. legumes) decrease the risk of prostate cancer
- limited/suggestive evidence that foods containing vitamin E decreases the risk of prostate cancer (matrix p. 76) [This has since been overturned by the SELECT trial as in the note above.]
- limited suggestive evidence that processed meat (i.e. preserved by smoking, curing or salting or the addition of chemical preservatives) increases the risk of prostate cancer (matrix p. 116)
- probable evidence that diets high in calcium increase the risk of prostate cancer. (matrix p. 129)
- limited/suggestive evidence that dairy products and milk increase the risk of prostate cancer (matrix p. 129)
Note that they were careful to distinguish between food containing a substance and vitamins.
The report also says the following regarding the pathogensis of prostate cancer (Chapter 7, p. 306):
The disease usually develops slowly and dysplastic lesions may precede cancer by many years or even decades. Extrapolations from autopsy studies suggest that most men would have prostate cancer if they lived to be more than 100. [PMID: 12642065] The number of prostate cancers found incidentally at autopsy, which had been asymptomatic and not a cause of death, suggests that small, localised prostate cancers can remain unrecognised for many years before progressing to a clinically significant form. Men are more likely to die with, rather than from, prostate cancer. [PMID: 12672328] [PMID: 12096083] [Full Text] The increased prostate cancer incidence in first-degree male relatives of women who have early onset breast cancer suggests a genetic predisposition.[PMID: 14580253] [Full Text]. Some studies propose that this may be linked to the BRCA genes. [PMID:14709740] [Full Text]. Growth factors, particularly IGF, as well as androgens have also been implicated in the development of prostate cancers. Serum levels of IGF-1 can be associated with prostate cancer independently of PSA levels. [PMID: 12122101] [Full Text] High levels of testosterone promote cell differentiation, which could protect against the development of this cancer. Therefore, declining levels of this hormone in older age may contribute to the development of this cancer. [PMID: 1292595]
Regarding inheritance we note that "Of 100 men who present with PC 74% will have sporadic PC while 26% will have clustered PC, i.e. evidence of genetic clustering. Of the 26% having clustered PC, 81% will have familial prostate cancer, FPC, and 19% will have hereditary prostate cancer, HPC." (See page 9 of PCRInsights, July 1999 which references [PMID: 7853589].) Also a recent study on colorectal cancer, lung cancer, breast cancer, ovarian cancer and prostate cancer in families concluded that "cancer-specific survival in parents predicts survival from the same cancer in their children" [PMID: 17921068]
The recommendations of the report are "are broadly similar to those that have been issued by other international and national authoritative organisations" (page xix) and their core is are summarized as the following in an AICR press release:
"Get and stay lean. Be physically active for at least 30 minutes a day as part of everyday life. Eat a diet that’s primarily composed of vegetables, fruits and other plant foods and limit meat. Limit or eliminate the consumption of alcohol."
More formally, the report has 10 recommendations which were unanimously agreed upon by the 21 experts:
- Body Fatness. Be as lean as possible within normal range of body weight. (Aim for a Body Mass Index, BMI, between 21 and 23. Box 12.3 on page 375 gives a chart that uses height and weight and gives an assessment of overweight in various categories, normal or underweight or try this BMI calculator or this chart.
- Physical Activity. Be physically active as part of everyday life. (Begin with 30 minutes brisk walking every day increasing increasing to 60 minutes of moderate or 30 minutes of vigorous exercise every day. Table 12.1 on page 377 quantifies exercise in terms of the Physical Activity Level, PAL, score.)
- Foods and Drinks that Promote Weight Gain. Limit consumption of energy dense foods (Also see: [link].) Avoid sugar drinks. (That means avoid high calorie foods, fast foods and processed foods.)
- Plant Foods. Eat mostly foods of plant origin. Eat at least 5 portions/servings (400g or 14 oz) of a variety of non-starchy vegetables and fruits every day. Eat relatively unprocessed cereals (grains) and/or legumes with every meal. Limit refined starchy foods.
- Animal Foods. Limit intake of red meat and avoid processed meats. (People who do eat red meat should consume less than 500g (18 oz) a week and very little if any processed meats.) The meat industry has contested this point of limiting red meat and processed food while the WCRF/AICR has responded to the meat industry statement.
- Alcoholic Drinks. Limit alcoholic drinks. If they are consumed limit consumption to no more than two drinks per day for men and one for women. (Despite the protective effect against coronary heart disease consumption of alcoholic drinks increases the risk of cancer and there is no level below which the risk is not increased.)
- Preservation, Processing and Preparation. Limit consumption of salt and avoid the consumption of moldy cereals (grains) and pulses (legumes). Such mold contains cancer causing alfatoxins.
- Dietary Supplements. Aim to meet nutritional needs through diet alone. (High-dose dietary supplements may be able to modify the risk of some cancers in specific, typically high-risk groups, but might have unexpected adverse effects when applied on a population basis. The report advises that supplementation be restricted to a clinical setting with medical advice.)
- Breastfeeding. Mothers to breast feed their children exclusively for six months with complementary feeding thereafter.
- Cancer Survivors. Cancer Survivors should follow the above recommendations for cancer prevention. (All cancer survivors should receive nutritional care from an appropriately trained professional.) In fact this recommendation seems to simply be a default as they were not able to find evidence to support much in the way of specific conclusions for cancer survivors.. With respect to food they stated "No conclusions can be derived from these results" (Chaper 9, p. 364), with regards to supplements they stated "The evidence from this review of trials does not show that micronutrient supplements have any benefits in cancer survivors. High-dose supplements may be harmful. Some micronutrients and other bioactive compounds are known to be toxic at high doses." (Chapter 9, p. 346) and with respect to physical activity they state that " Taken together, these trials provide some evidence for the benefit of physical activity on post-treatment quality of life in cancer survivors" (p. 347) but no evidence was found in favor of increased survival. Furthermore, with respect to prostate cancer Walter Willett of Harvard, who was a member of the expert panel has hypothesized that prostate cancer is different in younger and older men which, if confirmed, would certainly call into question the idea that the steps that reduce the risk of prostate cancer are the same as those which improve survival once one has it. See our previous post about this hypothesis [here].
There are also three additional recommendations of foods to avoid that only apply to specific regions. These are mate (found in South America), Cantonese-style salted fish (found in southern China) and arsenic contaminated water (found in many places around the world). (See Box 12.5 on page 392.)
One intriguing point made in the report (see Box 2.5 on page 46) is that
Restriction of energy intake from food is the most effective single intervention for preventing cancer in experimental animals. It increases the lifespan of rodents, and suppresses tumour development in mice. In addition, energy restriction can suppress the pro-cancer effects of many carcinogens in experimental animal models. [PMID: 12525670] Energy restriction leads to a reduction in cell proliferation. [PMID: 12525670] This may directly inhibit tumour growth, and also indirectly reduce cancer development by reducing overall proliferation, thus reducing the chances for incorrect DNA replication, or by preventing damaged DNA from being replicated. Reduced metabolism results in reduced generation of reactive oxygen species, and therefore less exposure of DNA to damaging oxygen radicals. Dietary energy restriction reduces levels of circulating IGF-166 [PMID: 15599926] and insulin, which are growth factors for many cells, including breast cancer. [PMID: 15607540] IGF-1 stimulates progression through the cell cycle from G1 to S phase, and high levels of insulin increase production of IGF-1.13 Energy restriction also decreases expression of cyclins and cyclin-dependent kinases (CDKs), and increases levels of CDK inhibitors, leading to reduced Rb phosphorylation and inhibited cell cycle progression.139 Energy restriction also decreases other inflammatory markers.[PMID: 12525670] Conversely, increased glucose levels associated with increased energy intake are associated with increased DNA synthesis and levels of some cyclins and CDKs.[link] Energy restriction may also create a pro-apoptotic environment and reduce blood vessel density, as shown in premalignant and malignant breast pathologies. [PMID: 14587868] It may also activate other protective pathways, such as the activation of protein deacetylases. [PMID: 15254550] The data on energy restriction must be interpreted with caution, as all studies have been performed in experimental animals and there is an absence of epidemiological and mechanistic data in humans. Therefore the relevance of these findings in experimental animals to the human condition is not yet clear.
The panel also reviewed reports by other bodies giving nutritional recommendations (see Chapter 10); however, these tended to mostly be aimed at cardiovascular benefits.
Chapter 11 lists a number of unanswered questions that further research may wish to pursue.
Note that one of the expert panel members is Walter Willett of Harvard whose work was featured in an earlier post on this blog: Willett Divides Prostate Cancer Into Four . Another expert panel member whose work has been featured on this blog is Claus Leitzmann who worked on the study that is the subject of this post: Calcium Increases Prostate Cancer Risk in Smokers .
The following news release discusses the relationship between growth and cancer that the report discusses but which is not discussed here as it seems less related to prostate cancer.
The [Cancer Process Foldout] is quite hard to read on screen so we have created a table based on it here:
|Fetal Expoxure||nutrient availability, fetal growth, material stress (infection, illness), maternal low protein|
|Body Composition||Obesity, Central Obesity, Adult Obtained Height, Metabolic Syndrome||Energy restriction|
|Cell Proliferation||n-6 PUFA, Insulin-like growth factor, Insulin, Leptin, Oestrogen, Obesity||Organosulphur compounds, Energy restriction, Flavonoids, Retinoids, Selenium, Indole-3-carbinol, n-3 PUFA|
|Carcinogens, other environmental exposures||Reactive oxygen species, Aflatoxin, N-nitroso compounds, Heterocyclic amines, Polycholinated biphenyls, inflammation, Phase I enzymes||zinc, curcumin, lycopene, Vitamin A, E, C, Flavonoids, Isothiocyanates, Selenium, Indole-3-carbinol, Energy restriction, Phase II enzymes|
|DNA Repair||Low folate, Malnutrition, Damaged DNA Repair||DNA repair, Selenium, Folate, Vitamin A, Coenzyme Q10|
Aptosis, Genistein, Retinoids, Polyphenols, Vanilloids, Indole-3-carbinol, n-3 PUFA
Insulin-like growth factor