This Article Abstract Full Text (PDF) All Versions of this Article: 1055-9965.EPI-06-0517v1 16/3/538    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kurahashi, N. Search for Related Content PubMed PubMed Citation Articles by Kurahashi, N. Related Collections Epidemiology Epidemiology: Nutritional Epidemiology

Soy Product and Isoflavone Consumption in Relation to Prostate Cancer in Japanese Men

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan

Requests for reprints: Shoichiro Tsugane, Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan. Phone: 81-3-3542-2511; Fax: 81-3-3547-8578. E-mail: stsugane{at}ncc.go.jp

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

 
The incidence of prostate cancer is much lower in Asian than Western populations. Environmental factors, such as dietary habits, may play a major role in the causation of prostate cancer. Although isoflavones have been suggested to show a preventive effect against prostate cancer in animal experiments, the results of epidemiologic studies are inconsistent. Here, we conducted a population-based prospective study in 43,509 Japanese men ages 45 to 74 years who generally have a high intake of isoflavones and low incidence of prostate cancer. Participants responded to a validated questionnaire, which included 147 food items. During follow-up from 1995 through 2004, 307 men were newly diagnosed with prostate cancer, of which 74 cases were advanced, 220 cases were organ localized, and 13 cases were of an undetermined stage. Intakes of genistein, daidzein, miso soup, and soy food were not associated with total prostate cancer. However, these four items decreased the risk of localized prostate cancer. In contrast, positive associations were seen between isoflavones and advanced prostate cancer. These results were strengthened when analysis was confined to men ages >60 years, in whom isoflavones and soy food were associated with a dose-dependent decrease in the risk of localized cancer, with relative risks for men in the highest quartile of genistein, daidzein, and soy food consumption compared with the lowest of 0.52 [95% confidence interval (95% CI), 0.30-0.90], 0.50 (95% CI, 0.28-0.88), and 0.52 (95% CI, 0.29-0.90), respectively. In conclusion, we found that isoflavone intake was associated with a decreased risk of localized prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(3):538–45)

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

 
The incidence of prostate cancer is much lower in Asian than in Western populations (1). However, Japanese migrants to the United States and Brazil have an increased incidence (2, 3), and the incidence of latent or clinically insignificant prostate cancer in autopsy studies among men from Asian countries and the United States is similar (4, 5). It has therefore been suggested that environmental factors may play an important role in the progression of prostate cancer. Asian populations consume large quantities of soy food that contained isoflavones such as genistein and daidzein (6). Mean serum or plasma concentrations of isoflavones in Japanese men are 10 to 100 times higher than those in men from the United Kingdom (7) and Finland (8). Moreover, Morton et al. (9) reported a higher concentration of daidzein in the prostatic fluid of Asian men than in Western men. Genistein and daidzein exhibit anticarcinogenic properties and estrogenic activity in vitro and have shown a protective effect against prostate cancer development in some animal studies (6). On these bases, isoflavones have been recognized as key substances that may decrease the incidence of prostate cancer in Asia. However, previous findings from epidemiologic studies regarding isoflavone or soy food intake and prostate cancer are equivocal (10-17).

This inconsistency may be due to errors in exposure measurement and limited variation in soy intake. Some of the previous epidemiologic studies investigated association between prostate cancer and a single soy food only, such as tofu or soy milk, and most were conducted in Western countries, in which physiologically meaningful amounts of soy are not consumed (10-12). Here, we investigated the association between isoflavone intake and risk of prostate cancer in a prospective study in Japanese who consume large amounts of soy.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

 
Study Population
The Japan Public Health Center–Based Prospective Study was initiated in 1990 for cohort I and in 1993 for cohort II. The study design has been described in detail previously (18). Cohort I included those residents ages 40 to 59 years who had registered their addresses in five public health center areas (Iwate, Akita, Nagano, Okinawa, and Tokyo). Cohort II included those residents ages 40 to 69 years who had registered in six public health center areas (Ibaraki, Niigata, Kochi, Nagasaki, Okinawa, and Osaka). The Tokyo subjects were not included in the data analysis because incidence data were not available. This study was approved by the institutional review board of the National Cancer Center, Tokyo, Japan. The initial cohort consisted of 68,557 men.

Food Frequency Questionnaire
At baseline, participants completed a self-administered questionnaire that assessed information on lifestyle factors, medical, and smoking histories. The food frequency questionnaire (FFQ) in the baseline survey had 44 food items for cohort I and 52 food items for cohort II with four (cohort I) or five (cohort II) frequency categories but without standard portions/units. In contrast, the 5-year follow-up survey included a self-administered FFQ, which included lifestyle factors, medical history, and 147 food and beverage items with standard portions/units and nine frequency categories. Owing to this greater detail, the present study therefore used the 5-year follow-up survey as baseline and followed the subjects from 1995 for cohort I and from 1998 for cohort II until 2004. After the 5-year follow-up survey, 128 subjects were found to be ineligible and were excluded because of non-Japanese nationality (n = 28), late report of emigration occurring before the start of the follow-up period (n = 97), incorrect birth data (n = 3), and subjects with self-reported prostate cancer (n = 21), leaving 58,427 men eligible for participation. Among eligible subjects, 46,001 men (79%) returned valid responses to the 5-year follow-up FFQ.

We dealt with two item groups: consumption of miso soup and soy food. Soy food referred to the consumption of "Tofu, Yushidofu (pre-drained tofu), Koyadofu (freeze-dried tofu), Aburaage (deep-fried tofu), Natto (fermented soybean), and soymilk," for which the major ingredient is soybeans. The questionnaire asked about the usual consumption of 147 foods and beverages during the previous year. The frequency of miso soup consumption was divided into six categories (almost never, 1-3 days/mo, 1-2 days/wk, 3-4 days/wk, 5-6 days/wk, and daily). Portion sizes were specified, and the amounts provided in three categories (less than half, same, and more than 1.5 times). One bowl of miso soup was calculated as 150 mL. Nine frequency categories were used for soy foods (almost never, 1-3 times per month, 1-2 times per week, 3-4 times per week, 5-6 times per week, once a day, 2-3 times per day, 4-6 times per day, and 7 times per day). Portion sizes were specified, and the amounts were determined in three categories (less than half, same, and more than 1.5 times). Ten frequency categories were used for soy milk (almost never, 1-3 times per month, 1-2 times per week, 3-4 times per week, 5-6 times per week, 1 glass per day, 2-3 glasses per day, 4-6 glasses per day, 7-9 glasses per day, and >9 glasses per day). The total consumption of miso soup (mL/d) and soy food (g/d) was calculated from these responses, whereas that of isoflavones (daidzein and genistein) was calculated using values in a specially developed food composition table for isoflavones in Japanese foods (19, 20).

Validity was assessed among subsamples using 14- or 28-day dietary records. Spearman's correlation coefficients between the energy-adjusted intake of miso soup and soy food consumption from the questionnaire and from dietary records were 0.54 and 0.53 for cohort I and 0.48 and 0.52 for cohort II, respectively, whereas those for energy-adjusted intake of daidzein and genistein were 0.65 and 0.65 for cohort I and 0.49 and 0.48 for cohort II, respectively. Moreover, Spearman's correlation coefficients for daidzein and genistein between energy-adjusted intakes from FFQ and those from serum concentration were 0.26 and 0.40, respectively, and with those from creatinine-adjusted urinary excretion were 0.22 and 0.33, respectively (21). These correlation coefficients are considered acceptable (22). With regard to the reproducibility of estimations between two questionnaires administered 1 year apart, respective correlation coefficients for the energy-adjusted intake of miso soup, soy food, daidzein, and genistein were 0.80, 0.64, 0.75, and 0.75 for cohort I and 0.75, 0.57, 0.53, and 0.51 for cohort II (23-25).

Among the 46,001 men who responded to the questionnaire, 2,492 who reported extreme total energy intake (<800 or >4,000 kcal) were excluded, leaving 43,509 men for analysis.

Follow-up
Subjects were followed from the 5-year follow-up survey until December 31, 2004. Changes in residence status, including survival, were identified annually through the residential registry in each area or, for those who had moved out of the study area, through the municipal office of the area to which they had moved. Generally, mortality data for residents included in the residential registry are forwarded to the Ministry of Health, Labour, and Welfare and coded for inclusion in the national Vital Statistics. Residency and death registration are required by the Basic Residential Register Law and Family Registry Law, respectively, and the registries are believed to be complete. Here, information on the cause of death was based on death certificates from the respective public health center for those who had not moved out of the original area. Among questionnaire respondents to the 5-year follow-up FFQ, 3,855 men (8.4%) died, 1,492 men (3.2%) moved out of the study area, and 66 men (0.1%) were lost to follow-up during the study period.

The occurrence of cancer was identified by active patient notification from major local hospitals in the study area and data linkage with population-based cancer registries, with permission from the local governments responsible for the cancer registries. Cases were coded using the International Classification of Diseases for Oncology, Third Edition (26). Death certificate information was used as a supplementary information source. The proportion of cases of prostate cancer first notified by death certificate was 0.9%. The ratio of incidence to mortality was 7.7. The registration rate as introduced by Parkin et al. (27) was 94.3%. The proportion of case patients with prostate cancer ascertained by death certificate only was 0.6%. These ratios were considered satisfactory for the present study. A total of 307 newly diagnosed prostate cancer cases were identified by December 31, 2004.

Finally, a population-based cohort of 43,509 men (18,105 in cohort I and 25,404 in cohort II) was established for analysis. During the 325,371 person-years of follow-up (167,611 in cohort I and 157,760 in cohort II), 307 cases of prostate cancer were newly diagnosed (156 in cohort I and 151 in cohort II).

Statistical Analysis
Person-years of follow-up were calculated for each man from the date of completion of the 5-year follow-up FFQ to the date of prostate cancer diagnosis, the date of emigration from the study area, or the date of death, whichever came first; or if none of these occurred, follow-up was through to the end of the study period (December 31, 2004). Men who were lost to follow-up were censored at the last confirmed date of presence in the study area. The crude incidence rate for prostate cancer was calculated by dividing the number of prostate cancer cases by the number of person-years. The relative risks (RR) of prostate cancer were calculated in quartile for the categories of miso soup consumption, soy food consumption, and isoflavone intake, with the lowest consumption category as the reference. RRs and 95% confidence intervals (95% CI) were calculated by the Cox proportional hazards model, adjusting for age at 5-year follow-up survey and study area (10 public health center areas) according to the SAS PHREG procedure (version 9.1; SAS Institute, Inc., Cary, NC). For further adjustment, additional possible confounders were incorporated into the model: smoking status (never, former, and current); alcohol intake (almost never, <3-4 days/wk, and >5 days/wk); marital status (yes/no); body mass index; and consumption of dairy foods, vegetables, fruit, and total fatty acids.

We conducted additional analyses according to the stage of prostate cancer. Advanced cases were defined by a diagnosis of extraprostatic or metastatic cancer involving lymph nodes or other organs. If this information was not available, advanced cases were defined as those with a high Gleason score (8-10) or poor differentiation. These criteria were selected to allow the identification of advanced cases with a high likelihood of poor prognosis. The remaining cases were organ localized. In this study, there were 74 advanced cases, 220 localized cases, and 13 (4% of total) cases of undetermined stage.

The trend was assessed by assigning ordinal values for categorical variables. All Ps were two sided, and statistical significance was determined at the P < 0.05 level.

	Results

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

 
Distribution of subject characteristics at the 5-year follow-up survey according to quartile of energy-adjusted isoflavone consumption is shown in Table 1 , in which the results for genistein were used as a surrogate for isoflavones owing to the high correlation among results for genistein, daidzein, miso soup, and soy food. Men with high genistein consumption were slightly older. Body mass index was higher in the highest category than in the other categories. The proportion of current smokers increased as genistein intake increased, whereas alcohol intake decreased. The proportion of men who live with their wife was lower in the lowest category than in the other categories. Screening-detected prostate cancer accounted for >40% of cases in all categories. Dairy food, fruit, vegetable, and total fatty acid consumption were positively correlated with genistein intake. As expected, soy food and miso soup increased as genistein intake increased and were highly correlated with it (P < 0.0001).

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

Our results support previous studies, which reported that soy food is protective for prostate cancer. Among case-control studies, Sonoda et al. (17) reported that natto (fermented soy) consumption showed a significantly decreasing linear trend for risk of prostate cancer in Japanese; Lee et al. (13) found that the highest intake of tofu and genistein had a statistically significant association with a decreased risk of prostate cancer in Chinese compared with the lowest intake; and Strom et al. (11) reported an inverse association between daidzein intake and prostate cancer risk in American men. Soy foods were also inversely related to prostate cancer in a large multicenter case-control study (12). In prospective studies, Jacobson et al. (10) reported that frequent consumption of soy milk was associated with a decreased risk of prostate cancer in Californian Adventist men. However, no association was seen between tofu consumption and a decreased risk of prostate cancer in Japanese men living in Hawaii (16), nor was tofu or miso soup significantly associated with prostate cancer risk in native Japanese (14). The reason these studies did not show a protective effect of soy foods on prostate cancer may have been due to their evaluation of a single soy food only or their failure to assess specific nutrients such as genistein or daidzein.

Studies in vivo and in vitro experiments have also shown a protective effect of isoflavones against prostate cancer development. Isoflavones possess weak estrogen activity, inhibit tyrosine protein kinases and angiogenesis, and reduce serum testosterone levels (6, 28, 29). Isoflavones also inhibit 5-reductase, an enzyme that metabolizes testosterone to dihydrotestosterone (30). Any or all of these mechanisms may explain the inverse association between isoflavones and localized prostate cancer seen here. Moreover, our results are plausible because the incidence of prostate cancer in Japanese is much lower than in Western men (1).

However, when the data were analyzed by stage, we found that the results differed between advanced and localized cancer. These results suggest that the effects of isoflavone may differ according to stage. One mechanism by which isoflavones reduce the risk of prostate cancer seems to involve estrogen receptor ß in prostate tissue (31), but cancer with higher metastatic potential is associated with the complete or partial loss of estrogen receptor ß expression (32-34). Moreover, animal studies in rats showed that the beneficial effects of a soy diet play a role in the early stages of tumor development but have no effect in invasive prostate cancer (35, 36). On this basis, isoflavones may prevent the early stages of prostate cancer development only. Clinically significant localized prostate cancer likely arises from latent cancer and then develop to advanced cancer with high mortality (4, 37). Given that the incidence of latent prostate cancer in Japanese men is the same as in Western men despite a lower incidence of prostate cancer (1, 4, 5), isoflavone may delay the progression of latent prostate cancer.

When we limited analysis to men ages >60 years, the association between isoflavone and localized prostate cancer was strengthened. Hoffman et al. (38) reported that men with cancers detected by prostate-specific antigen screening were more often younger than those men in whom cancer was clinically diagnosed. Our study also showed that the proportion of screening-detected cancers was higher (54.6%) in those men ages 60 years than in those ages >60 years (28.1%), although prostate-specific antigen screening information was available for only 70% of subjects. However, although we analyzed the association between localized prostate cancer and isoflavones after excluding screening-detected tumors, results did not change. Isoflavone may be protective for localized prostate cancer only in men ages >60 years and may not have a protective effect in the early stage of prostate cancer in younger men.

Our study has several methodologic strengths. First, it was a prospective design, which diminishes the probability of recall bias that is inherent to case-control studies. Second, we evaluated isoflavone intake using a validated questionnaire, and participants had a large variation in isoflavone consumption. One reason for the inconsistent findings for the association between soy food and prostate cancer in previous studies may be errors in exposure measurements and the small exposure variation in Western subjects. Third, we adjusted possible confounding factors to remove associations with other substances. It is also possible that a lifestyle associated with a high intake of soy food may have contributed to the risk of prostate cancer. In this study, the associations between isoflavones and prostate cancer were strengthened after adjustment for several confounding factors. Fourth, response rate was high (80%), and the proportion of subjects lost to follow-up was relatively low (0.1%).

On the other hand, the present study had several limitations. One was our inability to distinguish screening-detected cancer from total prostate cancer. It is possible that men who have health check-ups are more health conscious and may consume more soy food. However, such misclassification, if present, would lead to increase the risk of localized prostate cancer. Therefore, this inability to distinguish would not account for the decreased risk of localized prostate cancer. Another limitation was that the number of advanced prostate cancer cases was small. A larger sample size may have detected the positive effects of isoflavones on advanced prostate cancer with greater precision. Moreover, misclassification of exposure due to changes in isoflavone consumption during the study period might have occurred because we used information on consumption obtained at one point only. If present, however, such misclassification would underestimate the true relative risk.

In summary, we found that isoflavone intake was associated with a decreased risk of localized prostate cancer but tended to be associated with an increased risk of advanced prostate cancer. Recent interest has focused on whether isoflavones have chemopreventive effects. Given that Japanese consume isoflavones regularly throughout life, we do not yet know the period during which the effects of isoflavones on prostate cancer are preventive. Further research is required, including well-designed clinical trials in humans.

	Appendix A

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

 
Members of the Japan Public Health Center–Based Prospective Study Group (Principal investigator: S. Tsugane): S. Tsugane, M. Inoue, T. Sobue, and T. Hanaoka (Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo); J. Ogata, S. Baba, T. Mannami, and A. Okayama (National Cardiovascular Center, Suita); K. Miyakawa, F. Saito, A. Koizumi, Y. Sano, I. Hashimoto, and T. Ikuta (Iwate Prefectural Ninohe Public Health Center, Ninohe); Y. Miyajima, N. Suzuki, S. Nagasawa, Y. Furusugi and N. Nagai (Akita Prefectural Yokote Public Health Center, Yokote); H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki, Y. Watanabe, and Y. Miyagawa (Nagano Prefectural Saku Public Health Center, Saku); Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo, M. Irei, and H. Sakiyama (Okinawa Prefectural Chubu Public Health Center, Okinawa); K. Imoto, H. Yazawa, T. Seo, A. Seiko, F. Ito, and F. Shoji (Katsushika Public Health Center, Tokyo); A. Murata, K. Minato, K. Motegi, and T. Fujieda (Ibaraki Prefectural Mito Public Health Center, Mito); K. Matsui, T. Abe, M. Katagiri, M. Suzuki, and K. Matsui (Niigata Prefectural Kashiwazaki, Kashiwazaki and Nagaoka Public Health Center, Nagaoka); M. Doi, A. Terao, Y. Ishikawa, and T Tanoue (Kochi Prefectural Chuo-higashi Public Health Center, Tosayamada); H. Sueta, H. Doi, M. Urata, N. Okamoto and F. Ide (Nagasaki Prefectural Kamigoto Public Health Center, Arikawa); H. Sakiyama, N. Onga, H. Takaesu, and M. Uehara (Okinawa Prefectural Miyako Public Health Center, Hirara); F. Horii, I. Asano, H. Yamaguchi, K. Aoki, S. Maruyama, M. Ichii, and M. Takano (Osaka Prefectural Suita Public Health Center, Suita); S. Matsushima and S. Natsukawa (Saku General Hospital, Usuda); M. Akabane (Tokyo University of Agriculture, Tokyo); M. Konishi and K. Okada (Ehime University, Toon); H. Iso (Osaka University, Suita); Y. Honda and K. Yamagishi (Tsukuba University, Tsukuba); H. Sugimura (Hamamatsu University, Hamamatsu); Y. Tsubono (Tohoku University, Sendai); M. Kabuto (National Institute for Environmental Studies, Tsukuba); S. Tominaga (Aichi Cancer Center Research Institute, Nagoya); M. Iida and W. Ajiki (Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka); S. Sato (Osaka Medical Center for Health Science and Promotion, Osaka); N. Yasuda (Kochi University, Nankoku); S. Kono (Kyushu University, Fukuoka); K. Suzuki (Research Institute for Brain and Blood Vessels Akita, Akita); Y. Takashima (Kyorin University, Mitaka); E. Maruyama (Kobe University, Kobe); the late M. Yamaguchi, Y. Matsumura, S. Sasaki, and S. Watanabe (NIH and Nutrition, Tokyo); T. Kadowaki (Tokyo University, Tokyo); Y. Kawaguchi (Tokyo Medical and Dental University, Tokyo); H. Shimizu (Sakihae Institute, Gifu).

	Footnotes

 
Grant support: Grants-in-aid for Cancer Research (16shi-2), 3rd Term Comprehensive 10-Year-Strategy for Cancer Control (H16-sanjigan-010), and Research on Risk of Chemical Substances (H17-kagaku-014) from the Ministry of Health, Labour and Welfare of Japan and grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology (17015049).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: N. Kurahashi received a Research Resident Fellowship from the Foundation for Promotion of Cancer Research (Japan) for the 3rd Term Comprehensive 10-Year-Strategy for Cancer Control. Study Group members are listed in Appendix 1.

Received 6/28/06; revised 12/ 5/06; accepted 12/21/06.

	References

Top Abstract Introduction Materials and Methods Results Discussion Appendix A References

 

1. Parkin DM, Whelan SL, Ferlay J, Thomas DB. Cancer incidence in five continents. Vol. VIII. Lyon: IARC; 2002.
2. Tsugane S, de Souza JM, Costa ML, Jr., et al. Cancer incidence rates among Japanese immigrants in the city of Sao Paulo, Brazil, 1969-78. Cancer Causes Control 1990;1:189–93.[CrossRef][Medline]
3. Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 1991;63:963–6.[Medline]
4. Yatani R, Kusano I, Shiraishi T, Hayashi T, Stemmermann GN. Latent prostatic carcinoma: pathological and epidemiological aspects. Jpn J Clin Oncol 1989;19:319–26.[Free Full Text]
5. Muir CS, Nectoux J, Staszewski J. The epidemiology of prostatic cancer. Geographical distribution and time-trends. Acta Oncol 1991;30:133–40.[Medline]
6. Magee PJ, Rowland IR. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr 2004;91:513–31.[CrossRef][Medline]
7. Morton MS, Arisaka O, Miyake N, Morgan LD, Evans BA. Phytoestrogen concentrations in serum from Japanese men and women over forty years of age. J Nutr 2002;132:3168–71.[Abstract/Free Full Text]
8. Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 1993;342:1209–10.[CrossRef][Medline]
9. Morton MS, Chan PS, Cheng C, et al. Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom. Prostate 1997;32:122–8.[CrossRef][Medline]
10. Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control 1998;9:553–7.[CrossRef][Medline]
11. Strom SS, Yamamura Y, Duphorne CM, et al. Phytoestrogen intake and prostate cancer: a case-control study using a new database. Nutr Cancer 1999;33:20–5.[Medline]
12. Kolonel LN, Hankin JH, Whittemore AS, et al. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev 2000;9:795–804.[Abstract/Free Full Text]
13. Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev 2003;12:665–8.[Abstract/Free Full Text]
14. Allen NE, Sauvaget C, Roddam AW, et al. A prospective study of diet and prostate cancer in Japanese men. Cancer Causes Control 2004;15:911–20.[CrossRef][Medline]
15. Jian L, Zhang DH, Lee AH, Binns CW. Do preserved foods increase prostate cancer risk? Br J Cancer 2004;90:1792–5.[Medline]
16. Nomura AM, Hankin JH, Lee J, Stemmermann GN. Cohort study of tofu intake and prostate cancer: no apparent association. Cancer Epidemiol Biomarkers Prev 2004;13:2277–9.[Free Full Text]
17. Sonoda T, Nagata Y, Mori M, et al. A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet. Cancer Sci 2004;95:238–42.[CrossRef][Medline]
18. Otani T, Iwasaki M, Inoue M, Tsugane S. Body mass index, body height, and subsequent risk of colorectal cancer in middle-aged and elderly Japanese men and women: Japan public health center-based prospective study. Cancer Causes Control 2005;16:839–50.[CrossRef][Medline]
19. Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese intake of flavonoids and isoflavonoids from foods. J Epidemiol 1998;8:168–75.[Medline]
20. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr 2000;130:2243–50.[Abstract/Free Full Text]
21. Yamamoto S, Sobue T, Sasaki S, et al. Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a Japanese population in comparison with dietary records and blood and urine isoflavones. J Nutr 2001;131:2741–7.[Abstract/Free Full Text]
22. Willett W. Nutritional epidemiology. 2nd ed. New York (NY): Oxford University Press; 1998.
23. Ishihara J, Sobue T, Yamamoto S, et al. Validity and reproducibility of a self-administered food frequency questionnaire in the JPHC Study Cohort II: study design, participant profile and results in comparison with Cohort I. J Epidemiol 2003;13:S134–47.[Medline]
24. Sasaki S, Ishihara J, Tsugane S. Reproducibility of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I to assess food and nutrient intake. J Epidemiol 2003;13:S115–24.[Medline]
25. Tsugane S, Kobayashi M, Sasaki S. Validity of the self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I: comparison with dietary records for main nutrients. J Epidemiol 2003;13:S51–6.[Medline]
26. WHO. International classification of diseases for oncology. 3rd ed. Geneva (Switzerland): WHO; 2000.
27. Parkin DM, Chen VW, Ferlay J, Galceran J, Strorm HH, Whelan SL. Comparability and quality control in cancer registration. IARC Technical Report No. 19. Lyon: IARC; 1994.
28. Nagata C, Inaba S, Kawakami N, Kakizoe T, Shimizu H. Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men. Nutr Cancer 2000;36:14–8.[CrossRef][Medline]
29. Holzbeierlein JM, McIntosh J, Thrasher JB. The role of soy phytoestrogens in prostate cancer. Curr Opin Urol 2005;15:17–22.[CrossRef][Medline]
30. Evans BA, Griffiths K, Morton MS. Inhibition of 5 -reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 1995;147:295–302.[Abstract/Free Full Text]
31. Ganry O. Phytoestrogens and prostate cancer risk. Prev Med 2005;41:1–6.[Medline]
32. Horvath LG, Henshall SM, Lee CS, et al. Frequent loss of estrogen receptor-ß expression in prostate cancer. Cancer Res 2001;61:5331–5.[Abstract/Free Full Text]
33. Leav I, Lau KM, Adams JY, et al. Comparative studies of the estrogen receptors ß and and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol 2001;159:79–92.[Abstract/Free Full Text]
34. Fixemer T, Remberger K, Bonkhoff H. Differential expression of the estrogen receptor ß (ERß) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma. Prostate 2003;54:79–87.[CrossRef][Medline]
35. Landstrom M, Zhang JX, Hallmans G, et al. Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats. Prostate 1998;36:151–61.[CrossRef][Medline]
36. Bylund A, Zhang JX, Bergh A, et al. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice. Prostate 2000;42:304–14.[CrossRef][Medline]
37. Vij U, Kumar A. Phyto-oestrogens and prostatic growth. Natl Med J India 2004;17:22–6.[Medline]
38. Hoffman RM, Stone SN, Espey D, Potosky AL. Differences between men with screening-detected versus clinically diagnosed prostate cancers in the USA. BMC Cancer 2005;5:27.[CrossRef][Medline]

This article has been cited by other articles:

				L. Yan and E. L Spitznagel Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis Am. J. Clinical Nutrition, April 1, 2009; 89(4): 1155 - 1163. [Abstract] [Full Text] [PDF]

				N. Kurahashi, M. Iwasaki, M. Inoue, S. Sasazuki, and S. Tsugane Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center J. Clin. Oncol., December 20, 2008; 26(36): 5923 - 5929. [Abstract] [Full Text] [PDF]

				H. Ward, G. Chapelais, G. G.C. Kuhnle, R. Luben, K.-T. Khaw, and S. Bingham Lack of Prospective Associations between Plasma and Urinary Phytoestrogens and Risk of Prostate or Colorectal Cancer in the European Prospective into Cancer-Norfolk Study Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2891 - 2894. [Abstract] [Full Text] [PDF]

				M. Akhter, M. Inoue, N. Kurahashi, M. Iwasaki, S. Sasazuki, S. Tsugane, and for the Japan Public Health Center-Based Prospecti Dietary Soy and Isoflavone Intake and Risk of Colorectal Cancer in the Japan Public Health Center-Based Prospective Study Cancer Epidemiol. Biomarkers Prev., August 1, 2008; 17(8): 2128 - 2135. [Abstract] [Full Text] [PDF]

				N. Kurahashi, M. Inoue, M. Iwasaki, S. Sasazuki, a. S. Tsugane, and for the Japan Public Health Center-Based Prospecti Dairy Product, Saturated Fatty Acid, and Calcium Intake and Prostate Cancer in a Prospective Cohort of Japanese Men Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 930 - 937. [Abstract] [Full Text] [PDF]

				N. Kurahashi, S. Sasazuki, M. Iwasaki, M. Inoue, and Shoichiro Tsugane for the JPHC Study Group Green Tea Consumption and Prostate Cancer Risk in Japanese Men: A Prospective Study Am. J. Epidemiol., January 1, 2008; 167(1): 71 - 77. [Abstract] [Full Text] [PDF]

				M. C. Bosland and P. H. Gann Soy Isoflavone Consumption Is Not Associated with Increased Risk of Advanced Prostate Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2169 - 2169. [Full Text] [PDF]

				M. Stettner, S. Kaulfuss, P. Burfeind, S. Schweyer, A. Strauss, R.-H. Ringert, and P. Thelen The relevance of estrogen receptor-{beta} expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment Mol. Cancer Ther., October 1, 2007; 6(10): 2626 - 2633. [Abstract] [Full Text] [PDF]

				J. Mei, C. Wood, M. R. L'Abbe, G. S. Gilani, G. M. Cooke, I. H. Curran, and C. W. Xiao Consumption of Soy Protein Isolate Modulates the Phosphorylation Status of Hepatic ATPase/ATP Synthase {beta} Protein and Increases ATPase Activity in Rats J. Nutr., September 1, 2007; 137(9): 2029 - 2035. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 1055-9965.EPI-06-0517v1 16/3/538    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kurahashi, N. Search for Related Content PubMed PubMed Citation Articles by Kurahashi, N. Related Collections Epidemiology Epidemiology: Nutritional Epidemiology