Soy & Prostate Cancer

May 10, 2018

The difference between fermented and unfermented forms of soy protein and their benefits in prostate cancer is an interesting topic with varied research indicating different results.… As noted above recent research indicates that unfermented soy is associated with a decreased risk of PCa while fermented soy shows no associations with risk (Applegate et al., 2018) tempering earlier research that fermented soy may increase risk and cancer progression.

Why the difference between fermented and unfermented varieties? My readings found that, firstly, fermentation sees bacterial β-glucosidases cleave glycosidic linkages akin to digestive enzymes and gut microbiota altering soys structure (Islam et al., 2014). Secondly, a mechanism by which isoflavones exert anticarcinogenic effects is attributed to their antioxidant properties decreasing lipid peroxidation and oxidative DNA damage. Fermented soy generally contains added salt which with fermentation, the loss of oxygen and addition of acid, is causal to antioxidant property loss (Kim et al., 2011).

Contrary to the theory that fermented varieties show no association with risk, prior research indicates that fermented soy may contain nitroso compounds and high nitrate levels. Akin to their association with gastric cancer and via damage to stomach lining (increased permeability) and elevated endogenous N-nitroso formation (Kim et al., 2011) potential association with other forms of cancer including prostate cancer are thought to exist (Wu, Wang, Ho, & Giovannucci, 2013). It is theorised that nitrate may impact prostate cancer tissues where low pH/hypoxic conditions occur (Wu et al., 2013). That is, the conversion of nitrate to nitrite to NO occurs or does not occur as the case may be depending on ph/hypoxic conditions thus either facilitating inflammatory cancer conditions or antitumor effects (Wu et al., 2013)

Playing devil’s advocate even further, recent research also tends to suggest an alternative risk analysis with higher intakes of total isoflavones (genistein, daidzein and glycitein) potentially associated with an increased risk of prostate cancer advancement (Reger, Zollinger, Liu, Jones, & Zhang, 2018).

Research indicates that genistein intervention induces modulation of several genes (NOTCH3, JAG1, ADCY4, NEU1) involved in cell cycle, angiogenesis, immune response and intracellular signal transduction (Bilir et al., 2017). It is thought these genes potentialize molecular targets of genistein in prostate cancer pathways and prostate tumorigenesis (Bilir et al., 2017). This is seemingly further ratified by Reger et al., 2018 (n=27,004) who note that genistein may promote proliferation and metastasis of patient-derived prostate cancer cells by increasing epidermal growth factor receptor phosphorylation. Genistein is  also thought involved in G2/M cell cycle arrest activation and directs its effects at proteins involved in G2/M cancer checkpoints (Mukund, Mukund, Sharma, Mannarapu, & Alam, 2017).

Similarly, Reger et al., 2018 indicate that phytoestrogens may induce an estrogenic response due to structural similarity to 17β-estradiol (Reger et al., 2018) where estrogenic prostate carcinogenesis and prostate cancer progression (especially aggressive forms) manifests in genotoxic metabolites and regulation of estrogen receptor-β expression (Reger et al., 2018). In this instance it is thought the isoflavone daidzein may be causal to prostate cancer advancement due to estrogenic effect on the prostate gland (Reger et al., 2018).

This tends to indicate that potential benefits of soy and soy isoflavones is dependent on the stage and aggressiveness of the cancer and whether it’s application is for the prevention of or treatment of prostate cancer… In this, other recent studies suggest the timing of soy protein intake may impact prostate cancer potential more than the intake of soy itself. Bilir et al., 2017, indicate that higher soy intake during puberty when the prostate undergoes androgen-induced growth is likely more effective in prevention of prostate cancer than soy intake post diagnosis.

References

Applegate, C. C., Rowles, J. L., Ranard, K. M., Jeon, S., & Erdman, J. W. (2018). Soy consumption and the risk of prostate cancer: An updated systematic review and meta-analysis. Nutrients, 10(1). https://doi.org/10.3390/nu10010040

Bilir, B., Sharma, N. V., Lee, J., Hammarstrom, B., Svindland, A., Kucuk, O., & Moreno, C. S. (2017). Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer. International Journal of Oncology, 51(1), 223–234. https://doi.org/10.3892/ijo.2017.4017

Islam, M. A., Punt, A., Spenkelink, B., Murk, A. J., Rolaf van Leeuwen, F. X., & Rietjens, I. M. C. M. (2014). Conversion of major soy isoflavone glucosides and aglycones in in vitro intestinal models. Molecular Nutrition and Food Research, 58(3), 503–515. https://doi.org/10.1002/mnfr.201300390

Kim, J., Kang, M., Lee, J. S., Inoue, M., Sasazuki, S., & Tsugane, S. (2011). Fermented and non-fermented soy food consumption and gastric cancer in Japanese and Korean populations: A meta-analysis of observational studies. Cancer Science, 102(1), 231–244. https://doi.org/10.1111/j.1349-7006.2010.01770.x

Mukund, V., Mukund, D., Sharma, V., Mannarapu, M., & Alam, A. (2017). Genistein: Its role in metabolic diseases and cancer. Critical Reviews in Oncology/Hematology, 119, 13–22. https://doi.org/10.1016/j.critrevonc.2017.09.004

Reger, M. K., Zollinger, T. W., Liu, Z., Jones, J. F., & Zhang, J. (2018). Dietary intake of isoflavones and coumestrol and the risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. International Journal of Cancer, 142(4), 719–728. https://doi.org/10.1002/ijc.31095

Wu, T., Wang, Y., Ho, S.-M., & Giovannucci, E. (2013). Plasma Levels of Nitrate and Risk of Prostate Cancer: A Prospective Study. Cancer Epidemiology Biomarkers & Prevention, 22(7), 1210–1218. https://doi.org/10.1158/1055-9965.EPI-13-0134