Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study

Introduction

Soya foods are a rich source of isoflavones such as genistein and diadzein, a major group of phytoestrogens that have both weak oestrogenic and anti-oestrogenic activities.1 2 Phytoestrogens have been shown to alter endogenous oestrogen concentrations by binding competitively to oestrogen receptors,3 inhibiting important steroid biosynthetic enzymes,4 increasing the clearance of steroids from the circulation,5 and stimulating the production of sex hormone binding globulin.6 Soya foods also contain high amounts of dietary fibre, which has been shown to lower serum oestrogen by decreasing the concentration of intestinal β glucuronidase, increasing elimination of oestrogen through the faecal route, and reducing intestinal reabsorption.7 8

As endogenous oestrogens have a central role in the aetiology of endometrial cancer,9 factors that alter endogenous oestrogen concentrations, such as phytoestrogens and fibre, may be related to the risk of the disease. Circumstantial supporting evidence is available showing that Asian women have a lower incidence of endometrial cancer and eat more soya food than their Western counterparts.10 Analytical epidemiological studies on intake of soya foods and risk of endometrial cancer, however, have been few and inconsistent.11^–13

Given the dual effects of phytoestrogen, high intake of soya foods may reduce the risk of endometrial cancer among women with high exposure to oestrogen but increase the risk or have no effect on risk among women with low oestrogen exposure.14 We tested this hypothesis in a population based case-control study among Chinese women in Shanghai from 1997 to 2001.

Methods

Results

Cases and controls were well matched on age distribution (table 1). No major differences between cases and controls existed with respect to marital status, family income, total energy intake, or use of hormone replacement therapy. However, compared with controls, cases attained higher education; had an earlier age at menarche, later age at menopause, and longer duration of menstruation; had higher body mass index and waist:hip ratio; and were less likely to take regular exercise, drink alcohol, or use oral contraceptives. Cases were also more likely to have a family history of cancer, have been pregnant fewer times, and have consumed more meat and fish. No significant differences existed between cases and controls for fruit and vegetable intake. We adjusted all subsequent analyses for age, energy intake, and the above mentioned significant variables as potential confounders.

Table 2 shows the case-control comparisons for consumption of total soya foods, soya protein, and soya isoflavones. Women with endometrial cancer had a lower intake of total soya foods and almost every individual soya food investigated, as well as total soya protein and soya isoflavones, than did controls, although most differences did not reach statistical significance. The median intake of soya protein and isoflavones was 9.9 g/day and 40.5 mg/day for cases and 10.2 g/day and 42.5 mg/day for controls. The average intake of soya food among control women was comparable to that in our previous study.17

As shown in table 3, after adjustment for dietary and non-dietary risk factors, the odds ratios for endometrial cancer associated with the highest quarter of intake of soya protein, soya fibre, soya isoflavones, and fresh soya bean intake were 0.67 (95% confidence interval 0.48 to 0.92), 0.69 (0.51 to 0.94), 0.77 (0.56 to 1.05), and 0.63 (0.46 to 0.84), compared with the lowest quarter of intake. We also observed a dose-response relation for total intake of soya protein (P = 0.01), soya fibre (P = 0.02), and fresh soya beans (P = 0.01). Additional adjustment for total fruit and vegetable intake did not alter the association (data not shown). Intakes of soya protein, soya fibre, and soya isoflavones were highly correlated, making it difficult to separate their independent effects.

Table 4 summarises the results of the stratified analysis by menopausal status (premenopausal, postmenopausal), body mass index (< 25, ≥ 25), and waist:hip ratio (≤ 0.855, > 0.855). Although high soya food intake was related to a lower risk of endometrial cancer in all strata, the inverse association between intake of soya protein and risk of endometrial cancer was more pronounced among women with a higher body mass index (P for trend 0.01) or a higher waist:hip ratio (P for trend 0.01). We observed no multiplicative interactions. The association of soya intake with endometrial cancer did not vary by menopausal status, whether users of hormone replacement therapy (35 cases and 34 controls) were included in or excluded from the analysis.

Discussion

Incident rates of endometrial cancer vary more than 10-fold worldwide.18 In addition to host susceptibility, dietary factors may play an important role in this international variation. Asian countries have a low incidence of endometrial cancer and a high consumption of soya food. In our study population, the average intake of isoflavones from soya food was about 25 times that reported in a Western population (42.5 mg/day v 1.7 mg/day for controls),13 whereas the incident rate of endometrial cancer is only one fifth to one third that in Western countries.18

Soya isoflavones may play a role in the development of hormone related cancers, including endometrial cancer.19 Phytoestrogens have been shown to alter circulating concentrations of ovarian steroid hormones, prolong the menstrual cycle, alleviate symptoms of menopause, and enhance alkaline phosphatase activity in a human endometrial adenocarcinoma cell line, although evidence is not entirely consistent.19^–21 An inverse association between phytoestrogen consumption and risk of endometrial cancer was reported by Goodman in a multiethnic population and by Horn-Ross among Western women.12 13 However, legume intake was found to be associated with a slightly increased risk of endometrial cancer in an earlier study that we conducted among Chinese women.11 Some of these previous studies were not specifically designed to investigate the role of soya food, and the assessment of soya food intake was incomplete and sometimes mixed with other peas and beans.11 12 The sample sizes of the previous studies were relatively small, which limited the statistical power to evaluate the effect of soya food intake by menopausal status and body size.

This population based case-control study, specifically designed to test the hypothesis that soya food intake reduces endometrial cancer risk depending on endogenous hormone levels, indicates that usual consumption of soya foods by adults, measured as intake of either soya protein or soya isoflavones, is associated with a significantly reduced risk of endometrial cancer, particularly among women with a higher body mass index or waist:hip ratio. Although not all associations were statistically significant in subgroup analyses, the different measurements produced similar results.

Menopausal status, body mass index, and waist:hip ratio are associated with endogenous concentrations of sex hormones.22 23 Our finding of a more pronounced inverse association between soya food intake and risk of endometrial cancer among women with a higher body mass index or waist:hip ratio (P for trend < 0.05) are in line with our study hypothesis that soya food exerts an antioestrogenic effect in an oestrogen rich environment. However, the finding of a similar inverse association among premenopausal and postmenopausal women did not seem to support the above mentioned hypothesis or the findings from a recent US study that suggested a stronger effect of soya on endometrial cancer among postmenopausal women.13 Studies with measured oestrogen concentrations are needed to better understand the joint effect of soya and endogenous oestrogen on endometrial cancer risk.