The Science of Soy - The East Viewpoints: Part A6 - Soy and Cancers in Japanese

By Kyle J. Norton

Soy foods, including tofu have been in traditional Chinese diet over thousands of year, according to Chinese literature. The reduced risk of chronic disease, including metabolic syndrome such as cardiovascular diseases, obesity and diabetes and lesser menopause symptoms in advanced age, may be aided by eating a lot of soy food accompanied with large portion of vegetables and fruits. Indeed, according to the study, only 10% of women in the East are experience symptoms of menopause in advanced age compared to over 70% of their Western counterparts.
According to Dr. Mark Messina, Ph.D., Soy foods contributed from 6.5%8 to 12.8%7 of total protein intake in older adult in Japan.(b)

The approval of cardiovascular benefit of soy by FDA in 1999 accompanied with the discovery of health benefits in clinical studies over past decade, prompted the promotion and advertisement of soy's health benefits in every aspect in Western society. Evidences could be seen by walking through the supermarkets and drug stores. Soy supplements and products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers were widely available. According to the United Soybean Board’s 2004–2005, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.

Today, the promotion of soy are no longer existed, it may be results of discovery of adverse effect in single ingredient and animal studies, as intake of soy is associated to induce risk certain mammary cancers and infertility. The publication of the result have drawn many criticisms. According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate(a). Equol (4',7-isoflavandiol), an isoflavandiol metabolized from daidzein may be the causes, as 90% of Eastern population are equol producers but only 30% in the West.
The explanation of the positive effect of soy isoflavones in reduced risk of mammary cancers by University of Goettingen may be interesting, as researchers said" Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty.

Soybean is the genus Glycine, belonging to the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profits.
Nutrients
1. Carbohydrates
2. Dietary fiber
3. Fat
4. Protein
5. Essential amino acid
6. Vitamin A
7. Vitamin B6
8. Vitamin B12
9. Vitamin C
10. Vitamin K
11. Calcium
12. Iron
13. Magnesium
14. Phosphorus
15. Potassium
16. Sodium
17. Zinc
18. Etc.
Phytochemicals
1. Isoflavones
2. Genistein
3. Saponins
4. Beta-sitosterol
5. Daidzein

I. Soy in Eastern population
A. The Japanese population
Japan, an island nation in the Pacific Ocean, lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south(1c). According to Moriyama, Japanese women and men live longer and healthier than everyone else on Earth, it may be result of healthier Japanese diet and lifestyle. According to the World Health Organization, the Japanese have an average of 75 years healthy living with disability-free, it may be due to average soy intake 10 to 70 times higher than in Western people(1a)(1b).

A6. Soy and cancers in Japan population
Cancer, is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, become progressively worse and damaged other healthy tissues and sometimes spread to other organs in the body via lymph or blood and results may be in death.

Epidemiological studies, linking soy and soy products in reduced risk and treatment have been contradictive(1)(2)(3)(4), but in Japanese population, soy and its products have been found effectively in reduced risks of and treatment of cancers, it may be result of equol producer status or long term exposure since childhoods. Some researchers suggested that it may be result of traditional Japanese diet with high in soy, vegetables, fish.

1. Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer started in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) which supply the ducts with milk. There is also rare cases that breast cancer starts in other areas of the breast.
According to the evaluation based on a systematic review of epidemiologic evidence among the Japanese population, there is no associated of intakes of individual soy foods with the risk of breast cancer but evidence supported the biological plausibility of a protective effect of isoflavones on breast cancer risk(5). The study in the testing of oral administration of  IF-rich tablet (20 and 40 mg/day) on climacteric women,  showed  the product not only reduced risk of breast cancer but also improved of bone density, hypertension and climacteric symptoms, cardiovascular diseases, gynecological problems and possible immune potentiation(6)
Japanese women have lower incidence of and mortality from breast cancer, compared to Caucasians, it may be result of large amount intake soy protein and isoflavones, as high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects(7).

2. Lung cancer
Lung cancer is defined as a condition of the abnormal growth of the cells in the lung's tissue. Most common form of primary lung cancers are derived from epithelial cells. In Us, Lung cancer is the leading cause of cancer deaths, causing 158,683 people deaths, including 88,329 men and 70,354 women, according to 2007 statistic.
Soy intakes are associated to reduced risk of lung cancer with epidermal growth factor receptor (EGFR) mutations which play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs), according to the Aichi Cancer Center Research Institute.(8). In Asian populations, not only Japanese, in the review of total of 11 epidemiological studies that consisted of 8 case-control and 3 prospective cohort studies, although consumption of soy food is associated with lower lung cancer risk, intervention studies that use unified measures of soy intake are needed to fully characterize such an association due to different methods used to assess soy consumption across reviewed studies(9).
In deed, isoflavone intake was associated with a decreased risk of lung cancer in never smokers, but not in current or past smokers, according to a population-based prospective cohort study in 36,177 men and 40,484 women aged 45-74 y with no history of cancer at baseline in 1995-1999, conducted by the National Cancer Center Tokyo Japan(10).

3.  Bowel (Colorectal ) Cancer
Bowel cancer also known as colorectal cancer, is defined as a condition of the abnormal proliferation of cells in the colon, rectum, or vermiform appendix. Bowl is divided in 2 parts, the first part of the bowel, the small bowl, is involved with the digestion and absorption of food. The 2nd part, the large bowel which consist the the colon and rectum, is involved in absorption of water from the small bowel contents and broken down of certain materials in the feces into substances of which some of them to be re absorbed and reused by the body. Bowel cancer is relatively very common and slowly growing and progress cancer and in predictable way.
Bowel cancer is the third most commonly diagnosed cancer in developed countries, including US and Canada.
According to the Research Center for Cancer Prevention and Screening, National Cancer Center in Japan, in investigated association between dietary soy and isoflavone intake and incidence of colorectal cancer in a prospective cohort study of 83,063 Japanese men and women, ages 45 to 74 years, intake of isoflavones, miso soup, and soy food was not associated with colorectal cancer in either men or women. By colorectal cancer subsite, the risk of proximal colon cancer in men decreased with increasing consumption of isoflavones, miso soup, and soy food  in Compared with men in the lowest quartiles of isoflavones(11) and high isoflavone intake was associated with reduced risk of CI and MI in Japanese women, especially in postmenopausal women(12).
But for patients with Acromegaly, a syndrome that results when the anterior pituitary gland produces excess growth hormone (GH), the risk of colorectal cancer is increased substantially(13)(14).

4. Gastric cancer
Stomach cancer is defined as condition of abnormal growth of the mucus-producing cells of the inside lining of the stomach. Adenocarcinoma is the most common type of stomach cancer.
According to the National Cancer Center, Goyang, Korea, high level of consumption of non-fermented soy foods, rather than fermented soy foods, is associated to reducing GC risk, in the reviews of 20 studies assessing the effect of the consumption of fermented soy food on GC risk(15).
4-hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone (HEMF), a chemical constituent from of Japanese-style fermented soy sauce, reduced hydrogen peroxide concentration in human polymorphonuclear leucocytes stimulated by arachidonic acid or 12-O-tetradecanoylphorbol-13-acetate,through inhibition of carcinogenesis in this system by acting at the post-initiation stage, in female rats(16). Long-term effect of shoyu (Japanese soy sauce), in rat study did not appear to be a carcinogen in the rat; its prolonged use impaired neither health nor longevity but with a mild gastritis(17).

5. Cancer of Endometrium/Endometrial Cancer
Endometrium is the inner lining of the mammalian uterus and very susceptible hormone change, particular to menstrual cycle. Endometrial cancer is a late adulthood cancer defined as a condition of which the cells of the endometrial lining of uterus have growth uncontrollable or become cancerous as a result of the alternation of cells DNA. It's the fourth most common cancer among women overall, after breast cancer, lung cancer, and bowel cancer.
Greater consumption of isoflavone-containing foods is associated with a reduced risk of endometrial cancer in this population of nonhysterectomized postmenopausal women(18).
 In support to the above, the University of Hawaii, in the study of Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 which were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry, showed that plant-based diets low in calories from fat, high in fiber, and rich in legumes (especially soybeans), whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer(20). According to the National Cancer Center, Tokyo, Japan, in the study of Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey, researchers found that there was no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk(19).

6. Cervical Cancer
Cervix is the lower part of uterus that opens at the top of the vagina. Cervix acts an transition area for vaginal lining (squamous epithelium) change to uterus type (columnar epithelium) through the transitional area (squamous columnar epithelium) to host the development of the fetus. Cervical cancer is malignant neoplasm of the cervix uteri or cervical area caused by abnormal cells growth with alternation of cells DNA.
According to the study by, there was a the marginally significant inverse association between CIN3 and tofu and green leafy vegetables among Japanese women(21).

7. Prostate cancer
See The Science of Soy - The East Viewpoints: Part A3 - Soy and Prostate Cancer in Japanese Men

8. Thyroid Cancer
Thyroid is one of the largest endocrine glands found in the neck, below the Adam's Apple with the function of regulating the body use of energy, make of proteins by producing its hormones as a result of the stimulation of thyroid-stimulating hormone (TSH) produced by the anterior pituitary.
Thyroid cancer is defined as condition in which the cells in the thyroid gland have become cancerous.
According to the National Institute of Health Sciences, Tokyo, Japan, in the evaluation of the proliferating cell nuclear antigen labeling indices elevated in the ID diet(iodine-deficient diet) Female F344 rat groups suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency(22) but the study by showed the positive effect of dietary defatted soybean  in synergistically stimulated the growth of rat thyroid with iodine deficiency, partly through a pituitary-dependent pathway(23). No study was found in the search of the key word - soy and thyroid cancer in Japanese population" in  PubMed).

Taken altogether, Soy and its by products may be association to reduce risk and  for treatment certain cancers in Japanese population, including breast, lung, bowel, gastric, prostate, endometrial, cervical cancers, etc.  Due to lack of qualities of the studies found in PubMed, further study may be necessary to improve its validation even in Japanese population. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.
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References
(1) Long-term exposure to dietary sources of genistein induces estrogen-independence in the human breast cancer (MCF-7) xenograft model by Andrade JE¹, Ju YH, Baker C, Doerge DR, HelferichWG.(PubMed)
(2) Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations by Ju YH¹, Allred KF, Allred CD, Helferich WG.(PubMed)
(3) Daidzein-estrogen interaction in the rat uterus and its effect on human breast cancer cell growth by Gaete L¹, Tchernitchin AN, Bustamante R, Villena J, Lemus I, Gidekel M, Cabrera G, Astorga P.(PubMed)
(4) The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein by Pabona JM¹, Dave B, Su Y, Montales MT, de Lumen BO, de Mejia EG, Rahal OM, Simmen RC.(PubMed)
(5) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population by Nagata C¹, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Inoue M, Tsugane S, Sasazuki S; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan(PubMed)
(6) Isoflavones for prevention of cancer, cardiovascular diseases, gynecological problems and possible immune potentiation by Watanabe S¹, Uesugi S, Kikuchi Y.(PubMed)
(7) Phytoestrogens and breast cancer--promoters or protectors? by Rice S¹, Whitehead SA.(PubMed)
(8) Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among Japanese by Matsuo K¹, Hiraki A, Ito H, Kosaka T, Suzuki T, Hirose K, Wakai K, Yatabe Y, Mitsudomi T, Tajima K.(PubMed)
(9) Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies by Yang WS¹, Va P, Wong MY, Zhang HL, Xiang YB.(PubMed)
(10) Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan by Shimazu T¹, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, Tsugane S; Japan Public Health Center-based Prospective Study Group.(PubMed)
(11) Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study by Akhter M¹, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-Based Prospective Study Group(PubMed)
(12) Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: the Japan Public Health Center-based (JPHC) study cohort I by Kokubo Y¹, Iso H, Ishihara J, Okada K, Inoue M, Tsugane S; JPHC Study Group.(PubMed)
(13) The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study by Yamamoto M¹, Fukuoka H, Iguchi G, Matsumoto R, Takahashi M, Nishizawa H, Suda K, Bando H, Takahashi Y.(PubMed)
(14) Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels by Matano Y¹, Okada T, Suzuki A, Yoneda T, Takeda Y, Mabuchi H(PubMed)
(15) Fermented and non-fermented soy food consumption and gastric cancer in Japanese and Korean populations: a meta-analysis of observational studies by Kim J¹, Kang M, Lee JS, Inoue M, Sasazuki S, Tsugane S.(PubMed)
(16) Inhibition of benzo[a]pyrene-induced mouse forestomach neoplasia and reduction of H2O2 concentration in human polymorphonuclear leucocytes by flavour components of Japanese-style fermented soy sauce by Kataoka S¹, Liu W, Albright K, Storkson J, Pariza M.(PubMed)
(17) Long-term effect of shoyu (Japanese soy sauce) on the gastric mucosa of the rat by MacDonald WC, Dueck JW.(PubMed)
(18) Legume, soy, tofu, and isoflavone intake and endometrial cancer risk in postmenopausal women in the multiethnic cohort study by Ollberding NJ¹, Lim U, Wilkens LR, Setiawan VW, Shvetsov YB, Henderson BE, Kolonel LN, Goodman MT.(PubMed)
(19) Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study by Budhathoki S¹, Iwasaki M, Sawada N, Yamaji T, Shimazu T, Sasazuki S, Inoue M, Tsugane S; JPHC Study Group(PubMed)
(20) Association of soy and fiber consumption with the risk of endometrial cancer by Goodman MT¹, Wilkens LR, Hankin JH, Lyu LC, Wu AH, Kolonel LN.(PubMed)
(21) Association between dietary calcium and vitamin D intake and cervical carcinogenesis among Japanese women by Hosono S¹, Matsuo K, Kajiyama H, Hirose K, Suzuki T, Kawase T, Kidokoro K, Nakanishi T, Hamajima N, Kikkawa F, Tajima K, Tanaka H.(PubMed)
(22) Lack of effect of soy isoflavone on thyroid hyperplasia in rats receiving an iodine-deficient diet by Son HY¹, Nishikawa A, Ikeda T, Imazawa T, Kimura S, Hirose M.(PubMed)
(23) Dramatic synergism between excess soybean intake and iodine deficiency on the development of rat thyroid hyperplasia by Ikeda T¹, Nishikawa A, Imazawa T, Kimura S, Hirose M.(PubMed)