BY ALLAN R. HANDYSIDES

HEN I BEGAN THINKING ABOUT cancer, my mind went for a walk down memory lane. Scores of women and children came to my consciousness. Little kids with leukemia, bone cancers, muscle sarcomas. I thought of a baby born with a congenital neuroblastoma, which in those days was one of less than a score of cases reported. My mind conjured up women who had been diagnosed with breast cancer, ovarian cancer, and uterine cancer. I thought of a middle-aged woman in whom, at a routine examination, I found an enlarged kidney containing a renal cell cancer. Another in whom pelvic adenopathy alerted me to the diagnosis of malignant lymphoma. I thought of my dad and his prostate cancer.

Perhaps most tragic, I remembered a 32-year-old colleague who came to me for her routine checkup. Her pap smear revealed atypical cells suggestive of malignancy. My investigations, increasingly complex, did not reveal a source, and eventually after a couple of weeks I laparoscoped her, looking at the ovaries and pelvic organs. She had a 2-year-old child, and her insides looked clean and healthy, as expected in such a young woman, except for a peanut-sized lesion on the ovary.

Noting this, I scanned the peritoneum extremely carefully and meticulously. Some tiny salt grain irregularities on the peritoneum caught my attention. I biopsied these, as well as the ovary. Imagine my sorrow in having to communicate a diagnosis of widespread peritoneal and ovarian cancer. Imagine my patient's difficulties in her two-year losing battle for survival.

Where Do We Begin?
If prevention were understood and easy, these cases may not have occurred. Advances in our understanding are being made daily. For example: the new vaccine against human papilloma virus may well reduce cervical cancer to a fraction of its current prevalence. The screening procedures employed by many physicians are directed at detecting malignant change before it can spread to distant areas. Yet despite all these diagnostic and therapeutic advances, prevention obviously is the optimal approach. Some clear-cut relationships, such as that between smoking and cancer, point to obvious preventive measures. Do not start the use of tobacco!

Many other cancers do not have such obvious correlated causes. Can we alter our risk of cancer? Current information suggests there is a definite role for diet to play in reducing some cancer risks, just as there is for exercise and the abstinence part of our health message, for both alcohol and tobacco cause cancers.

Cancer is not a specific or single disease. Each type of cancer is specific to the tissue in which it arises, but cancers do share certain common features. The cellular division in cancer is uncontrolled and rapid, leading the cells to lose their tissue specificity to a greater or lesser extent. The stickiness between cells is reduced, making them more able to break off and migrate to other organs and tissues, where new colonies of cancer may grow. These colonies are called metastases.

The deoxyribonucleic acid (DNA) of the cell nucleus regulates cell division. Modification or damage to the DNA may interfere with this regulation. The actual division of cells requires several nutrients, such as cofactors (vitamins) and proteins. It is logical to ask whether diet could play a role in either the prevention or causation of cancer.

Some specific cancers are difficult to study because their prevalence and incidence in a community can be so low that valid deductions are not possible. A concept of "relative risk" permits the evaluation of dietary effects against controlled or general background populations. Factors of genetics, environment, and lifestyle have to be balanced out so as to reduce the chance of their interfering with results. This making of "all other things equal" is not easy. The risk, usually over a one-year period, of a cancer in a population eating the diet under consideration is compared to the risk in another population matched for other factors such as age, gender, etc. A relative risk of one means there is no difference. Less than one: less risk; more than one: more risk.

Dietary factors are prime targets for observation, because there are many ways they can affect us. Most have direct contact with the digestive tract. Some influence "bowel transit time." Some alter the biochemical environment by influencing the chemistry of colonic fluids and the metabolic activity of colonic bacteria. Some increase concentrations of fatty acids and secondary bile acids, which may decrease the risks of rapid cellular proliferation.

Protective factors, such as vitamins, flavonoids, and certain minerals, can influence the cellular function of cells within the body's internal organs. Foods may contain compounds known to be carcinogenic-for example, nitrosamines, produced in meat as it is heated to high temperatures, perhaps over a barbecue. Other foods may contain enzymes that protect by breaking down carcinogens. An example would be the isothiocyanates of cruciferous vegetables (broccoli, cabbage, brussels sprouts, etc).¹ Fruits and vegetables contain a number of antioxidants, such as vitamin C, beta carotene, vitamin E, and flavonoids. These could theoretically be anticarcinogenic through reducing DNA damage done by oxidizing free radicals. Vitamin C reduces the conversion of nitrites and nitrates to nitrosamines, so lessening the risk of this carcinogen. Folic acid helps in the synthesis of DNA,² so helping to keep the cell's nucleus healthy. Some substances may engage tissue hormone receptors, then either stimulate or block functions that may modify a cell division. Lignins, found in grains and seeds, and isoflavones, found in legumes, contain these phytoestrogens and could influence breast or prostate tissues.

Another potential cancer-promoting factor is obesity.³ Obesity is often associated with insulin resistance in the tissues, which leads to higher blood insulin levels. Some have suggested that higher insulin levels may correlate to increased cancer risk, so regular consumption of foods with a high glycemic index, i.e., rapidly raising blood sugars, might be associated with persistently increased insulin levels. Examples of foods with high glycemic indices are: white rice, refined flours, potatoes, and refined sugar. Complex carbohydrates, as found in whole foods such as beans, grains, and nuts, are much less likely to cause elevated insulin levels.⁴ Of course, obesity promotes higher insulin levels⁵ in its own right by creating tissue insulin resistance.

Vitamin D metabolites have been shown to reduce the rate of cell division in many tissues, dietary Vitamin D influences blood levels, and could affect the rates of cancer both in animals and humans.⁶

An association between meat eating and cancer has been shown in several studies.⁷ Increased risks of cancer of the stomach, colon, rectum, pancreas, bladder, breast, uterus, and ovary have been noted in those who eat more meat. Whether persons eating a high meat diet have reduced intake of the protective fruits and vegetables, and the role played by such reduction, is not absolutely clear at this point. It may be helpful to try to tease out some of the known dietary correlations with common cancers of specific organs.

Nearly 100,000 new cases occur per year in the United States, with some 48,000 deaths per year, and a five-year survival rate of 63 percent makes this a serious condition.⁸

Drs. Singh and Fraser⁹ reported in the American Journal of Epidemiology (148 [1998]:761-774) that colon cancer increased with the consumption of meats. Both red and white meats were associated with increased risk. Interestingly, white meats were associated with significantly greater risks of colon cancer than the red meats. These same investigators also found that protection against colon cancer lay in the legume group. This Adventist Health Study found also that the hazard of meat eating in relationship to colon cancer was predominant in nonlegume eaters. In fact, it is suggested that eating legumes (beans, chickpeas, lentils, etc.) protects both meat eaters and vegetarians. So obviously, if one eats meat, one would be wise to eat lots of beans.

Obesity in Adventist men, but not women, was also associated with increased colon cancer. A nonvegetarian low-legume-consuming obese male has a 5.1 times greater risk of colon cancer than a lean vegetarian who also rarely eats legumes.¹⁰ Calcium and folate are also thought to reduce colon cancer risks, which may explain some of the studies showing that dairy has a colon cancer protective effect.¹¹

Though more prevalent (198,000 new cases per year) than colon cancer, prostate cancer is associated with fewer deaths (31,500 patients). The prostate is a sex-hormone-responsive organ, and so prostate cancer can theoretically have a window of opportunity for intervention through this avenue. Phytoestrogens found in foods have been suggested as potential mediators of effect on prostate cancer development. Studies, including the Adventist health studies, have reported dietary relationships with prostate cancer, such as greater risks with meat and fish intake, and reduced risks with dried fruits, citrus, nuts, tomatoes, and legumes.¹² Yet it should be noted that careful multivariate analysis failed to confirm these suggestions.

In considering the evidence, one must understand that the numbers of cases involved in a study, the ability to control variables, and the statistical weight of the evidence make it that not all studies are reliable. This is why we repeatedly try to cool the jets of some enthusiasts who pick up any study that supports their ideas. Such reckless use of data may eventually harm the acceptance of good and useful practices, which in the long run is counterproductive.

In 1995 Baldwin et al., at the American Biological Association meeting in New Orleans, presented a paper suggesting that tomatoes were protective against prostate cancer. Cooking tomatoes releases the lycopenes and potentiates their availability. Support for the role of tomatoes was given by a large cohort study of health professionals reported by Gann, et al.¹³ Though weak associations between meat intake and prostate cancer have been suggested,¹⁴ and fats, particularly saturated fats, are suggested¹⁵ as culprits. The association is of a low order-a possible association, not a probable one.

While calcium has been suggested as reducing colon cancer, it has been suggested, but on rather weak evidence, that there may be a link between increased calcium intake and prostate cancer.¹⁶ While on the topic of prostate cancer we would be remiss if the small subgroup of Adventist men taking more than one glass of soy milk per day, in whom a protective effect was reported, was not mentioned. Though a small study,¹⁷ this dovetails nicely with the report by Severson et al., who noted a protective effect that they related to a tofu intake of more than five portions per week.¹⁸

Female breast cancer is clearly related to factors such as the maternal history of breast cancer, the age at first child (the risk increases with age), the age at menopause (increased risk with age), and education level (again increasing with an increased level). These hold for both Adventist and non-Adventist populations. Ecologic studies have shown that different countries have rates of breast cancer, but picking the contributing factors from the multiple possible causes is not easy. Factors being considered are fat intake, animal products, soy products, fruits, and vegetables.

There is inconclusive evidence that meat consumption influences the risk of breast cancer, and though fat has been suggested as playing a causative role, pooled analysis of seven studies (including the Adventist Health Study) could not provide conclusive evidence that more fat changed the risks of breast cancer. In a study that the investigators felt provided weak evidence, increased cheese consumption was correlated with an increasing risk of breast cancer.¹⁹ Much as we Adventists like to use this study, integrity demands that we recognize the evidence as weak.

Protective effects of serum carotenoids such as lutein, alpha- carotene, beta-carotene, were reported by Toniolo, but because the study did not adjust for other dietary factors, noncarotenoid components of fruits and vegetables could be active.²⁰ Extracted carotenoids in tablet forms have not been shown to provide the benefits they do in the whole food.

Soy products may protect against breast cancer through their phytoestrogens,²¹ or by reducing blood estrogen levels.²² Dietary factors may play a role in lung cancer, for which fruits seem protective, and pancreatic cancer, in which meat may play a causative role.

I could summarize by saying that there is no convincing association between diet and breast cancer.

Meat consumption significantly increases the risk of colon cancer and probably the risk of prostate, bladder, and ovarian cancer.

Legumes lower rates of pancreatic cancer, colon cancer, and possibly prostate cancer.

Fruit consumption lowers rates of lung cancer, probably prostate cancer, pancreatic cancer, and possibly ovarian cancer.

Tomatoes may protect against prostate cancer and ovarian cancer.

Soy milk more than once per day reduces the risk of prostate cancer.

Cheese may be associated with higher risks of breast and ovarian cancer, though more evidence is necessary.

While we have learned a great deal since Ellen White taught that a plant based diet was superior to a flesh food-based diet, there is still a lot to discover as to how such a recommendation works.

This issue of the Adventist Review encourages you to participate in Loma Linda University's latest study. No matter what your diet or lifestyle, you can contribute to the fund of knowledge from which we can encourage the best possible lifestyle so that indeed in our health we give praise, thanks, and glory to God.

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¹ D. Verhoeven et al., in Cancer Epidemiol Biomarkers Prevention 5 (1996): 733-748.
² E. Giovannucci et al., in Journal of the National Cancer Institute 85 (1993): 875-884.
³ N. Potischman et al., in Journal of the National Cancer Institute 88 (1996): 756-758.
⁴ D. Jenkins et al., in American Journal of Clinical Nutrition 46 (1987): 968-975.
⁵ E. Mayer-Davis et al., in Diabetes Metabolism Research and Reviews 17 (2001): 137-145.
⁶ M. Lipkin and H. Newmark, in Journal of the American College of Nutrition 18 (1999): 3925-3975.
⁷ A. Tavani, C. La Vecchia, S. Gallus et al., in International Journal of Cancer 86 (2000): 425-428.
⁸ R. Greenlee et al., in Cancer Journal for Clinicians 51 (2001): 15-36.
⁹ P. Singh and G. Fraser, in American Journal of Epidemiology 148 (1998): 761-774.
¹⁰ A. Giacosa et al., in European Journal of Cancer Prevention 8, supplement 1 (1999): 553-560.
¹¹ M. Martinez et al., in Journal of the National Cancer Institute 88 (1996): 1375-1382; J. Kearney et al., in American Journal of Epidemiology 143 (1996): 907-917.
¹² B. Jacobsen et al., in Cancer Causes and Control 9 (1998): 553-557; P. Mills et al., in American Journal of Epidemiology 133 (1991): 230-239.
¹³ P. Gann et al., in Cancer Research 59 (1999): 1225-1230.
¹⁴ P. Gann et al., in Journal of the National Cancer Institute 86 (1994): 281-286.
¹⁵ L. Le Marchand et al., in Epidemiology 5 (1994): 276-282.
¹⁶ J. Chan et al., in American Journal of Clinical Nutrition 74 (2001): 549-554.
¹⁷ B. Jacobsen et al., in Cancer Causes and Control 9 (1998): 553-557.
¹⁸ R. Severson et al., in Cancer Research 49 (1989): 1857-1860.
¹⁹ P. Mills et al., in Cancer 64 (1989): 598-604.
²⁰ P. Toniolo et al., in American Journal of Epidemiology 153 (2001): 1142-1147.
²¹ L. J. Lu et al., in Cancer Research 60 (2000): 41, 12-21.
²² A. Wu et al., in Cancer Epidemiol Biomarkers Prevention 5 (1996): 901-906.

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Allan R. Handysides, M.B., Ch.B., F.R.C.P. (C), is director of the General Conference Health Ministries Department and one of the contributors to the Ask the Doctors column in the Adventist Review.