Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans
Autor: | Li Tang, Yue Wu, James L. Mohler, Zinian Wang, Gary J. Smith, Clayton M. Shanahan, Gissou Azabdaftari, Elizabeth T. H. Fontham, Qianqian Zhu, Elena Pop, Jeannette T. Bensen |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Genotype Epidemiology medicine.drug_class Organic Anion Transporters Single-nucleotide polymorphism Ancestry-informative marker White People Article 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate Internal medicine Biomarkers Tumor medicine Humans Alleles Cellular localization Aged business.industry Prostatic Neoplasms Middle Aged medicine.disease Androgen Black or African American Androgen receptor 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Biomarker (medicine) business |
Zdroj: | Cancer Epidemiol Biomarkers Prev |
ISSN: | 1538-7755 1055-9965 |
Popis: | Background: Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA). Methods: SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina–Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and in situ RNA hybridization in independent sets of prostate cancer cases. Results: Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (Pinteraction < 0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively. Conclusions: SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs. Impact: The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer. |
Databáze: | OpenAIRE |
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