Diet, Pesticides and Breast Cancer

According to the latest Canadian Cancer Society statistics, the incidence of breast cancer is now about 1 woman in 8, up from one in ~50 back in the 50’s. Some of the increase may be attributed to hormone use (contraceptives or hormone replacement after menopause), and increase in diabetes rates, but the importance of dietary factors in breast cancer has also been well documented. One thing is for sure, Genetics has not changed. As the incidence itself has increased so much, despite the progress in early detection and treatment, the rates of death have been stable between 1950 and 1990 for US white women, while they have actually increased slightly for black women! All this, despite the fact that smoking has been reduced dramatically, thanks to a great extent to the efforts of the US and Canadian National Cancer Institutes.

The Cancer Diet

The importance of diet in cancer prevention has been well documented. In a book by Dr. Richard Béliveau a Biochemistry professor at the University of Montreal, a list of foods that fight cancer was produced1. Some of it is summarized here.

Everybody has heard about the benefits of the “Mediterranean” diet (besides, it tastes good…). Lots of fruits and vegetables, olives and olive oil, meat and dairy in moderation. Epidemiological studies have shown that people following such a diet have less heart disease and cancer. More recently a group from Heidelberg (Germany) demonstrated that a key ingredient is olive oil and black olives2, as they contain an abundance of antioxidants that inhibit the initial development of cancer. Interestingly, it was also shown that polyphenols and oleic acid (the main fatty acid in olives) inhibit the expression of Her2, a gene found to be hyperactive in about 20% of breast cancers, although it is much less effective than Herceptin, the drug used to inhibit Her23.

Another important culinary compound that is particularly effective is turmeric, a yellow powder that is used in Indian curries. Turmeric has strong anti-inflammatory effects, mainly because of a substance called curcumin, which inhibits the growth of cells from a large number of cancers, including breast. Interestingly, curcumin was found to even inhibit the growth of breast cancer tumors that did not respond to chemotherapy with taxol, when the tumors were grafted onto mice4. For curcumin to be absorbed by the intestines, turmeric has to be mixed with pepper or ginger, as occurs in most curries.

Other foods that help the fight against cancer are berries, especially blackberries, blueberries, raspberries and strawberries. The ellagic acid found in them inhibits receptors that promote cell division and angiogenesis, ie the development of new blood vessels that tumors need to grow, but also stimulates the elimination of dangerous toxins that promote mutations5, 6. In addition, blueberries contain anthocyanidins that force cancer cells to commit suicide7.

It is important to note that many foods act together much better than each one in isolation. As an example, it has been reported that the combination of tomatoes and broccoli had an anti-tumor activity that was greater than either one alone, at least for prostate cancer8. This could be because each substance may block a specific pathway that a cancer cell uses to divide uncontrollably, while most cancers use a number of different pathways, hence the advantage of a combination of inhibitors.

Alcohol is a carcinogen. However, substances such as resveratrol present in red wine inhibit several cancer genes9, 10, so that a glass of red wine a day is OK. In any event, avoid refined sugars. These are absorbed quickly, so that the sudden surge of sugar in the bloodstream triggers the production of high amounts of insulin by the pancreas that stimulates not only the insulin receptor, but also the receptor of a growth factor that has been linked to cancer (insulin-like growth factor or IGF). Sugar consumed as part of other foods is absorbed more slowly so that it does not trigger such a peak of insulin and IGF activation.

Finally, the beneficial effects of green tea are well documented. In 1999 a paper in the Journal Nature showed that green tea is capable of blocking angiogenesis11. Green tea contains polyphenols called catechins such as epigallocatechin galate (EGCG) which inhibit the formation of blood vessels necessary to feed the tumor, and also inhibit cancer metastasis by blocking specific receptors12.

According to the data of Dr. Béliveau, garlic, leeks, scallions, Brussel sprouts, cauliflower, cabbage, kale, broccoli are the best for breast cancer, while potatoes, lettuce, cucumber, peppers are less effective (summarized in13). But, there is a problem: Fruits and vegetables often contain pesticide residues, which may raise health concerns. In fact, over 90% of dietary exposure to pesticides is in fruits and vegetables14, 15.

Effect of Pesticides

Chemical pesticide use largely originated after the Second World War, as many pesticides evolved from war-related research. Despite anecdotal evidence, it is very difficult to measure the effect of pesticides upon human health. This is because consumers of organic food, which contains little if any synthetic pesticides15, tend to have at the same time healthier dietary patterns overall, be less obese, have lower rates of diabetes (all risk factors for cancers including breast) and to exercise more. (To definitively answer this question one would have to intentionally feed pesticides to human beings, which of course is not possible).

Government pesticide risk assessment methods to determine acceptable levels of pesticide residues in food are either too insensitive or were not designed to address the many complex risks posed by contemporary pesticide use. According to data from the Canadian Food Inspection Agency (CFIA, 2014)*, pesticide residues were detected in 73% of fresh fruit and vegetable samples in Canada, although contamination was below acceptable levels for most. However, setting the bar on what is “acceptable” is controversial (Auditor General, 2015)**. Besides, pesticide residue data and dietary risk estimates fail to reflect real world exposures and do not take into account the fact that people are often exposed to multiple pesticides on a given foodstuff or on a given day, sometimes leading to synergistic effects16. To top it off, many cancers such as breast cancer take many years to develop, so that the association is very difficult to establish.

Despite this uncertainty, it is important to take into account the fact that cancer patients in remission (ie survivors) may be more sensitive to carcinogens than the general population. Although nobody can ever know when the first mutation happened to start the cancer ball rolling, that first mutation makes the cell grow slightly faster than normal. As the DNA is copied more times than normal, this increases the chances of more mistakes ie mutations happening, as one of the ~6 billion bases are copied with each division. Most often, the mutation is such that the cell dies; this cell is never noticed. However, if the mutation is such that it makes the cell escape the controls of cell division that govern normal cells and grows faster, it will be selected for. This process, termed “tumor progression”, is repeated many times over many years, so that the speed of growth of the tumor is increased exponentially with time. Eventually, the tumor cells acquire the ability to invade surrounding tissues and cancer is declared. That is, a benign tumor may be on the verge of becoming malignant by the acquisition of just one or a few more mutations, which may be caused by a carcinogen in food. If a chemical causes mutations in eg cultured cells, this is an indication that it may also be able to act as a human carcinogen (and cancer survivors may be more sensitive to it), even if its effect cannot be measured precisely because of many confounding factors.

In spite of these difficulties, epidemiological studies point to negative health effects of certain pesticides. According to a committee of the US National Academy of Sciences (1993) infants exposed in utero and children face significant risks in cognitive development from low-level pesticide exposures during critical windows of development, and some exposures may have serious life-long consequences.

Of great relevance to breast cancer is the fact that organic crops also have a lower content of the metal cadmium than conventional crops due to differences in fertilizer usage and soil organic matter17. Cadmium exposure has been linked to breast cancer in women18.

The International Agency for Research on Cancer (IARC) of the World Health Organization reported on the carcinogenic effects of several commonly used organophosphate insecticides and the herbicide glyphosate. Their assessment, published in Lancet in 201519, reviewed the available evidence, which is mostly from cell culture or animal studies, or human occupational exposure (e.g. farmers spraying pesticides, workers in factories producing them).

IARC classifies substances regarding their carcinogenicity to humans in 5 groups: 1 (Carcinogenic), 2A (Probably carcinogenic), 2B (Possibly carcinogenic), 3 (Not classifiable as to its carcinogenicity), 4 (Probably not carcinogenic)***.

According to the IARC report, tetrachlorvinphos and parathion insecticides were classified as “possibly carcinogenic to humans” (Group 2B). Tetrachlorvinphos is banned in the European Union, but in the US it is still used in flea collars, while parathion use has been severely restricted since the 1980’s. The insecticides malathion and diazinon were classified as “probably carcinogenic to humans” (Group 2A), based on occupational exposure data (prostate cancer and non-Hodgkin’s lymphoma) and cause chromosomes to break, which is a known mechanism of carcinogenesis.

The broad-spectrum herbicide glyphosate has been detected in the blood and urine of agricultural workers. It was found to induce DNA and chromosomal damage in mammals, and in human cells in culture. One study also reported increases in chromosomal damage in residents of several communities after spraying of glyphosate20. As a result of these studies, IARC classified glyphosate as “probably carcinogenic to humans” (Group 2A).

The insecticides are generally sprayed on the crops during the growing season, which may allow time for breakdown or dissipation before harvest. The herbicide glyphosate has a long history of use in killing weeds prior to seeding, and more recently, it is being sprayed on crops that have been genetically modified to tolerate glyphosate, for weed control (ordinary crops would be killed by the herbicide).

However, there is another use for glyphosate: It is widely used as a “desiccant”, that is, it is applied to facilitate drying of mature crops such as wheat and canola, and to burn down in-crop weeds, which can affect moisture of the harvested crop. That is, the herbicide goes on our food right before harvest, with hardly any time to decay. To top it off, the most “healthy” kind of bread, whole wheat or bran bread, contains the highest amounts of herbicide, as it sticks to the outside of the grain…

Besides pesticide residues, of great relevance to breast cancer is the use of estrogens in e.g. beef and poultry in Canada. These are well documented human carcinogens for all estrogen-responsive tissues, including breast. In fact, the rise in breast cancer in the 90’s has been attributed to the use of contraceptive pills and hormone-replacement therapy after menopause. A genetically engineered product – recombinant bovine growth hormone – has been linked to cancer. It is in use in the US, but is not permitted in Canada or in most of the rest of the world. In any event, consumption of organic meat can minimize the risk of breast cancer or relapse, especially regarding estrogen-receptor positive cancers.

There are other, important, health-related effects of organic consumption. The prevalent use of antibiotics in conventional animal production is a key driver of antibiotic resistance, which is a big problem as anybody who has ever been hospitalized would testify. The prevention of animal disease and restricted use of antibiotics, as practiced in organic production, is minimizing this risk, with considerable benefits for public health overall. This is on top of the reduction in contamination of ground water with carcinogens that we would end up ingesting too.

The demand for organic produce and meats has increased by double digits annually, for at least 20 years. Big grocery chains now offer specials at reasonable prices. This makes the choice for organics much easier15. Are cancer rates going to go down eventually, back to what they were in the 50’s?

That would be real progress!

The Canadian Cancer Society and the National Cancer Institute of Canada (and their US equivalents) have been at the forefront of the fight against smoking. To a great extent thanks to their efforts smoking has been reduced dramatically in the last 50 years. Perhaps pesticides are the next target, and it should be easier, because these agencies would not be up against an addiction. Nobody feels the urge to eat roundup, very much unlike smoking. Stay tuned!


References

1. Beliveau, R., Gingras, D. Foods that fight cancer: Preventing cancer through diet. Random House, New York (2006).

2. Owen, R.W. et al. Olives and olive oil in cancer prevention. Eur J Cancer Prev 13, 319-326 (2004).

3. Menendez, J.A., Vellon, L., Colomer, R. & Lupu, R. Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (Herceptin) in breast cancer cells with Her-2/neu oncogene amplification. Ann Oncol 16, 359-371 (2005).

4. Carter, A. Curry compound fights cancer in the clinic. J Natl Cancer Inst 100, 616-617 (2008).

5. Labrecque, L. et al. Combined inhibition of PDGF and VEGF receptors by ellagic acid, a dietary-derived phenolic compound. Carcinogenesis 26, 821-826 (2005).

6. Hanausek, M., Walaszek, Z. & Slaga, T.J. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther 2, 139-144 (2003).

7. Seeram, N.P. et al. Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. J Agric Food Chem 54, 9329-9339 (2006).

8. Canene-Adams, K. et al. Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas. Cancer Res 67, 836-843 (2007).

9. Surh, Y.J. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3, 768-780 (2003).

10. Kotha, A. et al. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein. Mol. Cancer Ther 5, 621-629 (2006).

11. Cao, Y. & Cao, R. Angiogenesis inhibited by drinking tea. Nature 398, 381 (1999).

12. Jankun, J., Selman, S.H., Swiercz, R. & Skrzypczak-Jankun, E. Why drinking green tea could prevent cancer. Nature 387, 561 (1997).

13. Servan-Schreiber, D. Anti-cancer; a new way of life. (Harper-Collins, 2009).

14. Benbrook, C.M. Minimizing pesticide dietary exposure through the consumption of organic food. The Organic center (2004).

15. Holzman, D.C. Organic food conclusions don’t tell the whole story. Environ Health Perspect 120, A458 (2012).

16. Mesnage, R., Defarge, N., Spiroux de Vendomois, J. & Seralini, G.E. Major pesticides are more toxic to human cells than their declared active principles. Biomed Res Int 2014, 179691 (2014).

17. Baranski, M. et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. Br J Nutr 112, 794-811 (2014).

18. Nagata, C. et al. Cadmium exposure and the risk of breast cancer in Japanese women. Breast Cancer Res Treat 138, 235-239 (2013).

19. Guyton, K.Z. et al. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol 16, 490-491 (2015).

20. Bolognesi, C., Carrasquilla, G., Volpi, S., Solomon, K.R. & Marshall, E.J. Biomonitoring of genotoxic risk in agricultural workers from five colombian regions: association to occupational exposure to glyphosate. J Toxicol Environ Health A 72, 986-997 (2009).

*Canadian Food inspection agency (CFIA). National chemical residue monitoring program. 2013-2014 report. Page 25, Table 5.

**Office of the auditor general of Canada. Reports of the commissioner of the environment and sustainable development. Report 1, pesticide safety. Fall 2015. https://corporateeurope.org/food-and-agriculture/2017/06/did-efsa-lie-press-its-glyphosate-assessment http://www.businessinsider.com/ap-epa-denies-petition-to-ban-pesticide-used-on-crops-2017-3

***IARC report: http://www.foodinsight.org/what-is-IARC-International-Agency-for-Research-on-Cancer-WHO?gclid=EAIaIQobChMIz4jD287t1AIVgTRpCh1NAAZhEAAYAiAAEgI-d_D_BwE

For a great compendium of the refereed evidence on pesticides and specific cancers, see:

https://www.beyondpesticides.org/resources/pesticide-induced-diseases-database/cancer

Leda Raptis, Ph.D., Professor, DBMS, Queen’s University

and Ann Clark, Ph.D., Associate professor, retired, University of Guelph.

February 15, 2018