Menopause Live - IMS Updates

Date of release: 27 April, 2009

Colorectal cancer risk and soy food intake in women

The incidence of colorectal cancer has been reported to be lower in Asians than in Caucasians, even though rapid increases in Asian countries, particularly in Japan, have been noticed [1,2]. Higher soy food consumption by Asians than by Caucasians has been thought to be one of the possible reasons for the difference. A recently published prospective cohort study [3] evaluated the relationship between soy food intake and colorectal cancer risk in women in Shanghai, China. The study examined 68,412 women 40–70 years of age by assessing their usual soy food intake at baseline (1977–2000) and again at follow-up (2000–2002) through in-person interview with a validated questionnaire. During a mean follow-up of 6.4 years, 321 colorectal cancer cases were identified. The results showed that total soy intake was inversely associated with colorectal cancer risk. Each 5-g/day increase in intake of soy foods was associated with 8% reduction in risk (95% confidence interval (CI) 3–14%). Women in the highest tertile of intake had a risk of 0.67 (95% CI 0.49–0.90) compared with those in the lowest tertile (p for trend = 0.008). This inverse association was primarily confined to postmenopausal women. The authors concluded that consumption of soy foods may reduce the risk of colorectal cancer in postmenopausal women.


For a long time, there has been speculation that soy food intake might be one of the significant factors leading to a lower incidence of hormone-related malignancies, such as colorectal and breast cancers, in the Asian population than in the Western population.
Many studies have evaluated this hypothesis in Asia, particularly in China and Japan, where populations consume significant amount of soy products in their daily lives. Soy and its products are the most abundant source of isoflavones in human diets and are rich in fiber, calcium and folic acid.
Isoflavones have a diphenolic structure similar to that of 17β-estradiol and have been shown to bind preferentially to estrogen receptor (ER)-β but weakly to ER-α [4,5]. 
The level of ER-β protein in colorectal cancer was reported to be significantly reduced in both men and women, but more so in men (p = 0.04 vs. women). Furthermore, in men, the ER-β level was significantly lower in poorly differentiated tumors than in moderately differentiated tumors (p < 0.03), whereas, in women, poor differentiation of the tumor was not associated with a significant decrease in ER-β level [6].
In vitro studies have shown that isoflavones act primarily as estrogen agonists in a low-estrogen environment, whereas they act as estrogen antagonists in a high-estrogen environment [7]. The inverse association of soy consumption with colorectal cancer risk seen predominantly in postmenopausal women may suggest that the effect of soy on colorectal cancer may, at least in part, be due to its estrogen-like effect.
In contrast to the Shanghai study, a cohort study from Japan [8], which surveyed 83,063 men and women, indicated that the intake of isoflavones, miso soup, and soy food had no substantial effect on the risk of colorectal cancer in Japanese men and women. Nevertheless, the different results of these two studies could be due to the fact that the Japanese study did not make any distinction between fresh and preserved (fermented) soy foods (such as miso soup in Japan) in their dietary assessment and/or data analysis. 
Theoretically, isoflavones and/or soy foods could be effective in decreasing colorectal cancer risk in men more than in women, because of the difference in their ER-β expression patterns. Actually, the Japanese study [8] showed that the risk of proximal colon cancer in men decreased with increasing consumption of isoflavones, miso soup and soy food.
Recently, there has been increasing attention by medical societies on the relation of postmenopausal hormone replacement therapy (HRT) and colorectal cancer. The results of the Women’s Health Initiative study, which showed a significant decrease in colorectal cancer with estrogen plus progestin therapy and a non-significant decrease with estrogen-alone therapy, have stimulated discussions and comments both in the NAMS First-to-Know and in Editorials in the IMS journal, Climacteric. Whether plant-generated estrogen, especially soy isoflavones, can be used as a natural alternative to HRT needs to be further evaluated.
The issue of soy food consumption and the prevalence of colorectal cancer remain intriguing, yet controversial, and await further research.


Ko-En Huang
Chang Gung Memorial Hospital, Kaohsiung Hsien, Taiwan


  1. International Agency for Research on Cancer. Cancer incidence in five continents. Lyon, France: IARC, 2003.

  2. Potter JD, Slattery ML, Bostick RM, Gapstur SM. Colon cancer: a review of the epidemiology. Epidemiol Rev 1993;15:499-545.

  3. Yang G, Shu XO, Li H, et al. Prospective cohort study of soy food intake and colorectal cancer risk in women. Am J Clin Nutr 2009;89:577-83. Published February, 2009.

  4. Lechner D, Kallay E, Cross HS. Phytoestrogen and colorectal cancer prevention. Vitam Horm 2005;70:169-98.

  5. Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogen with estrogen recptor beta. Endocrinology 1998;139:4252-63.

  6. Nussler NC, Reinbacher K, Shanny N, et al. Sex-specific differences in the expression levels of estrogen receptor subgroups in colorectal cancer. Gend Med 2008;5:209-17.

  7. Hwang CS, Kwak HS, Lim HJ, et al. Isoflavone metabolites and their in vitro dual functions: they can act as an estrogenic agonist or antagonist depending on the estrogen concentration. J Steroid Biochem Mol Biol 2006;101:246-53.

  8. Akhter M, Inoue M, Kurahashi N, et al. Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study. Cancer Epidemiol Biomarkers Prev 2008;17:2128-35.