4. Discussion
tumor, prostate cancer
PROLIFERATION, TUMOR, PROSTATE CANCER
In this randomized controlled dietary intervention study of patients with prostate cancer, an increased intake of phytoestrogens did not affect the serum of concentrations of testosterone, SHBG, and IGF-1. However, a trend of decreased risk of increased concentration of estradiol was found in participants with the TC/CC genotype of ERβ. In the intervention group, participants with the TC/CC genotype decreased serum concentrations of SHBG during the intervention compared to participants with the TT genotype, who increased their concentrations.In one of the genotype groups of ERβ, we found a trend of a decreased risk of increasing estradiol concentration, comparing the intervention and control groups. This is in contrast to another study that demonstrated an increase in plasma concentrations of phytoestrogens and increased concentrations of serum estradiol, although the blood concentrations of phytoestrogens were lower than in our study [We did not find any effect of the phytoestrogen intervention on serum concentrations of testosterone, IGF-1, and SHBG. This is in line with several other studies finding no effect on blood concentrations of testosterone, IGF-1, and SHBG [In the intervention group, the two genotype groups of ERβ had opposites effects on SHBG concentration, participants with the genotype of TC/CC decreased their concentrations during the intervention, and participants with TT genotype increased their concentrations. This suggests that the genotype of ERβ may affect the serum concentrations of hormones. To our knowledge, this is the first study to investigate the effect of phytoestrogens on serum hormones depending on the genotype of ERβ. ERβ has an important role in, e.g., hormonal and protein regulation and transcription, and thus the genotype of ERβ could play a role in these different responses [We found that the intervention diet increased the plasma concentrations of several phytoestrogens. Elevated plasma phytoestrogen concentrations have been confirmed in similar intervention studies [The strengths of this study include the randomized design and the fact that blood concentrations of phytoestrogens were measured. The results are also based on a large clinical study with a low dropout rate. Even if the number of dropouts would be large enough to affect the results, we do not expect the results of the participants who dropped out from the study to differ from the rest of the study population. A limitation of the present study is the change from crushed to whole flaxseeds, which probably decreased the absorption of lignans [In conclusion, our findings suggest that a high intake of phytoestrogens may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ but does not affect serum concentrations of testosterone, IGF-1, and SHBG. However, the effect on SHBG concentration differed across the ERβ genotype groups. The effect of the genotype of ERβ on hormone concentrations in patients with prostate cancer should be confirmed in future studies. Further research is needed to investigate whether elevated plasma concentrations of phytoestrogens have a beneficial effect in terms of reduced tumor proliferation and prolonged survival for patients with prostate cancer.  