In our study, the beneficial effect of soy consumption was found among the female population but not among the male population. Chandanos
et al. reported that women with a longer fertility life and those who are on hormone replacement therapy seem to have a decreased risk of gastric cancer, and men who have been treated with estrogen for prostate cancer also have a decreased risk
61. The mechanism for this decrease in risk remains unknown.
Isoflavones have a similar structure to 17β-estradiol and act as estrogen agonists or antagonists in environments of different estrogen levels, which may contribute to the different beneficial effects of soy consumption in females and males62.
Moderate heterogeneity was found from some of our results. First, while every study adjusted for age and gender in the calculation of risk estimates, not every included study has been adjusted for total energy intake and body mass index, which are confounding factors
63.
Second, the effects that soy intake has on GI cancer risk might differ among different preparations or fermentations of soy foods. Three included studies adjusted and analyzed fermented and non-fermented soy food6, 40, 46. The high intake of non-fermented soy food was more likely to be inversely associated with gastric cancer risk6. A higher salt intake increased the risk of GI cancer, and miso soup, one of the soy subtypes, was considered a high salt food
12,
64. Third, the data gathering methods that were used might also contribute to the heterogeneity. Four studies relied on a personal interview, while the remaining studies came from the self-reported Food Frequency Questionnaires (FFQ)
28,
31,
39,
46. The participants may have different understandings of the questionnaire by different methods. Fourth, thirteen studies used a validated FFQ mixed with nine non-validated FFQs. The validated FFQ listed various types of soy foods, leading to precise estimates of soy or isoflavone intake. Fifth, we have pooled cohort studies and a nested case-control study with different estimates of OR, RR and HR. HR and OR were considered to be approximations of RR because CRC is a rare outcome in humans. We used a random effects method to determine when the heterogeneity (
I2) was larger than 40% to enhance the credibility of the results.
Our meta-analysis has several strengths. First, our study was based on only prospective studies, which enabled us to minimize the food exposure recall bias and selection bias. To our knowledge, this is the first time that the association between both GI cancer incidence and mortality with soy intake from prospective studies has been summarized. Most previous meta-analyses collected both retrospective and prospective studies. Woo
et al. (2013) reported that a case-control design created a significant association between the flavonoid subclasses and cancer risk, while cohort studies did not observe this association
14. Second, all included studies strictly followed our inclusion criteria, which made our results more stable. Third, our sample size is an important strength, as we included a total of 12,901 cancer cases from a total of 965,466 participants. Combining a large number of participants renders us sufficient power to detect potential, modest associations. Fourth, according to our sensitivity analysis, the inverse association did not vary with the exclusion of any single study.
Similar to all other meta-analyses, our study has some limitations. First, moderate heterogeneity was observed from some of our results. We have discussed the reasons above; however, the sensitivity analysis showed that our inverse association was stable and reliable. Second, the included studies were reported from different countries and populations and the measurement of soy intake and soy type varied among them.
In summary, no association was found between soy consumption and GI cancer incidence or mortality. A higher intake of soy product is associated with the decreased risk of overall GI cancer and gastric cancer, but not colorectal cancer. This protective effect was observed in females but not in males.