Effects of Soy Protein Isolate Consumption on Prostate Cancer Biomarkers in Men With HGPIN, ASAP, and Low-Grade Prostate Cancer

Abstract

Fifty-eight men at high risk of prostate cancer or with low-grade prostate cancer were randomly assigned to consume 1 of 3 protein isolates containing 40 g protein: 1) soy protein (SPI+, 107 mg isoflavones/d); 2) alcohol-washed soy protein (SPI–, <6 mg isoflavones/d); or 3) milk protein (MPI). Proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor, B-cell non-Hodgkin lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed in baseline and ending prostate biopsy cores. Serum collected at 0, 3, and 6 mo was analyzed for total and free prostate specific antigen (PSA). Consumption of SPI+ did not alter any of the prostate cancer tumor markers. Bax expression decreased from baseline in the SPI– group, resulting in lower Bax expression than the MPI group. PCNA expression also decreased from baseline in the SPI– group, but this was not different from the other 2 groups. PSA did not differ among the groups at 3 or 6 mo. Interestingly, a lower rate of prostate cancer developed in the soy groups compared to the milk group (P = 0.01). These data suggest that 6-mo SPI+ consumption does not alter prostate tissue biomarkers, SPI– consumption exerts mixed effects, and less prostate cancer is detected after 6 mo of soy consumption regardless of isoflavone content.

ACKNOWLEDGMENTS

Immunohistochemistry was performed by Kenji Takamura. The authors thank Kayla Vettling and Ellie Wiener for tissue scoring and Lori Sorensen, Nicole Nelson, and Mary McMullen for assistance with clinic visits and data entry. We are also quite grateful to the study participants for their time and dedication. The Soy and Prostate Cancer Prevention (SoyCaP) trial was supported by Grant DAMD 17–02–1–0101 (M. S. Kurzer) and W81XWH–06–1–0075 (J. M. Hamilton-Reeves) from the United States Army Department of Defense Prostate Cancer Research Program. The protein isolates were donated by The Solae Company, St. Louis, MO. Neither sponsor was involved in writing this report.

Notes

^aAll values are n (%). Abbreviations are as follows: SPI+, isoflavone-rich soy protein isolate (40 g soy protein, 107 mg isoflavones/day); SPI–, alcohol-extracted soy protein isolate (40 g soy protein, <6 mg isoflavones/day); MPI, milk protein isolate (40 g milk protein); PIN, prostatic intraepithelial neoplasia; ASAP, atypical small acini suspicious for prostatic adenocarcinoma; CaP, prostate cancer. Subjects were categorized by most advanced pathological diagnosis.

^aBaseline data are unadjusted means + SE. All other data are least-squares means adjusted for baseline measurement ± SE. Abbreviations are as follows: HSCORE, immunohistochemical histological score; SPI+, isoflavone-rich soy protein isolate (40 g soy protein, 107 mg isoflavones/day); SPI–, alcohol-extracted soy protein isolate (40 g soy protein, <6 mg isoflavones/day); MPI, milk protein isolate (40 g milk protein); Bax, B-cell non-Hodgkin lymphoma-2 (Bcl-2)-associated X protein; PCNA, proliferating cell nuclear antigen; EGFr, epidermal growth factor receptor. Means in a row without a common subscript letter differ (P < 0.05).

*significant within-group change from baseline (P < 0.05).

^bn = 14 for SPI+, n = 16 for SPI–, and n = 14 for MPI.

^cn = 14 for SPI+, n = 13 for SPI–, and n = 14 for MPI.

^dn = 15 for SPI+, n = 14 for SPI–, and n = 16 for MPI.

^en = 15 for SPI+, n = 14 for SPI–, and n = 13 for MPI.

^fn = 14 for SPI+, n = 14 for SPI–, and n = 13 for MPI.

^gn = 13 for SPI+, n = 13 for SPI–, and n = 12 for MPI.

^aBaseline data are unadjusted means ± SE. Differences are post-intervention minus baseline and are least-squares means adjusted for baseline measurement + SE. Abbreviations are as follows: PSA, prostate specific antigen; PSA %, free PSA/total PSA; SPI+, isoflavone-rich soy protein isolate (40 g soy protein, 107 mg isoflavones/day); SPI–, alcohol-extracted soy protein isolate (40 g soy protein, <6 mg isoflavones/day); MPI = milk protein isolate (40 g milk protein).

^bSample sizes listed at column headings are for all time points except 3 mo MPI (n = 17), 6 mo SPI+ (n = 18), and 6 mo SPI– (n = 19).

^aBaseline data are unadjusted means ± SE. Differences are postintervention minus baseline and are least squares means adjusted for baseline measurement ± SE. Abbreviations are as follows: PSA, prostate specific antigen; PSA density, total PSA/prostate volume; SPI+, isoflavone-rich soy protein isolate (40 g soy protein, 107 mg isoflavones/day); SPI–, alcohol-extracted soy protein isolate (40 g soy protein, <6 mg isoflavones/day); MPI, milk protein isolate (40 g milk protein). Means in a row without a common subscript letter differ (P < 0.05).