TY - JOUR
T1 - Association between cadmium and androgen receptor protein expression differs in prostate tumors of African American and European American men
AU - Neslund-Dudas, Christine M.
AU - McBride, Russell B.
AU - Kandegedara, Ashoka
AU - Rybicki, Benjamin A.
AU - Kryvenko, Oleksandr N.
AU - Chitale, Dhananjay
AU - Gupta, Nilesh
AU - Williamson, Sean R.
AU - Rogers, Craig G.
AU - Cordon-Cardo, Carlos
AU - Rundle, Andrew G.
AU - Levin, Albert M.
AU - Dou, Q. Ping
AU - Mitra, Bharati
N1 - Funding Information:
National Institute of Environmental Health Sciences (R01 ES011126 to B.A.R., R21 ES024379 to C.N.D.), Wayne State University, President's Research Enhancement Program (to C.N.D.) and Wayne State University/HenryFordHealth System INPHAASE program (to C.N.D.), National Center for Research Resources (NCRR) (UL1 RR024156 to R.B.M).
Publisher Copyright:
© 2018 Elsevier GmbH
PY - 2018/7
Y1 - 2018/7
N2 - Cadmium is a known carcinogen that has been implicated in prostate cancer, but how it affects prostate carcinogenesis in humans remains unclear. Evidence from basic science suggests that cadmium can bind to the androgen receptor causing endocrine disruption. The androgen receptor is required for normal prostate development and is the key driver of prostate cancer progression. In this study, we examined the association between cadmium content and androgen receptor protein expression in prostate cancer tissue of African American (N = 22) and European American (N = 30) men. Although neither overall tumor cadmium content (log transformed) nor androgen receptor protein expression level differed by race, we observed a race-cadmium interaction with regard to androgen receptor expression (P = 0.003) even after accounting for age at prostatectomy, smoking history, and Gleason score. African American men had a significant positive correlation between tumor tissue cadmium content and androgen receptor expression (Pearson correlation = 0.52, P = 0.013), while European Americans showed a non-significant negative correlation between the two (Pearson correlation = −0.19, P = 0.31). These results were unchanged after further accounting for tissue zinc content or dietary zinc or selenium intake. African American cases with high-cadmium content (>median) in tumor tissue had more than double the androgen receptor expression (0.021 vs. 0.008, P = 0.014) of African American men with low-cadmium level. No difference in androgen receptor expression was observed in European Americans by cadmium level (high 0.015 vs. low 0.011, P = 0.30). Larger studies are needed to confirm these results and if upheld, determine the biologic mechanism by which cadmium increases androgen receptor protein expression in a race-dependent manner. Our results suggest that cadmium may play a role in race disparities observed in prostate cancer.
AB - Cadmium is a known carcinogen that has been implicated in prostate cancer, but how it affects prostate carcinogenesis in humans remains unclear. Evidence from basic science suggests that cadmium can bind to the androgen receptor causing endocrine disruption. The androgen receptor is required for normal prostate development and is the key driver of prostate cancer progression. In this study, we examined the association between cadmium content and androgen receptor protein expression in prostate cancer tissue of African American (N = 22) and European American (N = 30) men. Although neither overall tumor cadmium content (log transformed) nor androgen receptor protein expression level differed by race, we observed a race-cadmium interaction with regard to androgen receptor expression (P = 0.003) even after accounting for age at prostatectomy, smoking history, and Gleason score. African American men had a significant positive correlation between tumor tissue cadmium content and androgen receptor expression (Pearson correlation = 0.52, P = 0.013), while European Americans showed a non-significant negative correlation between the two (Pearson correlation = −0.19, P = 0.31). These results were unchanged after further accounting for tissue zinc content or dietary zinc or selenium intake. African American cases with high-cadmium content (>median) in tumor tissue had more than double the androgen receptor expression (0.021 vs. 0.008, P = 0.014) of African American men with low-cadmium level. No difference in androgen receptor expression was observed in European Americans by cadmium level (high 0.015 vs. low 0.011, P = 0.30). Larger studies are needed to confirm these results and if upheld, determine the biologic mechanism by which cadmium increases androgen receptor protein expression in a race-dependent manner. Our results suggest that cadmium may play a role in race disparities observed in prostate cancer.
KW - African American
KW - Androgen receptor
KW - Cadmium
KW - Heavy metal
KW - Prostate cancer
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U2 - 10.1016/j.jtemb.2018.04.006
DO - 10.1016/j.jtemb.2018.04.006
M3 - Article
C2 - 29773186
AN - SCOPUS:85046037827
VL - 48
SP - 233
EP - 238
JO - Journal of Trace Elements in Medicine and Biology
JF - Journal of Trace Elements in Medicine and Biology
SN - 0946-672X
ER -