SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: A prospective cohort study and meta-analysis Journal Article
| Authors: | Rajanala, S. H.; Plym, A.; Vaselkiv, J. B.; Ebot, E. M.; Matsoukas, K.; Lin, Z.; Chakraborty, G.; Markt, S. C.; Penney, K. L.; Lee, G. S. M.; Mucci, L. A.; Kantoff, P. W.; Stopsack, K. H. |
| Article Title: | SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: A prospective cohort study and meta-analysis |
| Abstract: | Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians’ Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69–0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy. © 2024 Oxford University Press. All rights reserved. |
| Keywords: | adult; controlled study; aged; major clinical study; single nucleotide polymorphism; case control study; cancer radiotherapy; cancer staging; outcome assessment; follow up; prospective study; cohort analysis; genotype; genetic variation; cancer hormone therapy; prostate cancer; gleason score; questionnaire; prostatectomy; cancer specific survival; androgen deprivation therapy; hydroxymethylglutaryl coenzyme a reductase inhibitor; genotyping; cancer prognosis; human; male; article; immunological antineoplastic agent; expression quantitative trait locus; solute carrier organic anion transporter 1b1; solute carrier organic anion transporter 1b3 |
| Journal Title: | Carcinogenesis |
| Volume: | 45 |
| Issue: | 1-2 |
| ISSN: | 0143-3334 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-01-01 |
| Start Page: | 35 |
| End Page: | 44 |
| Language: | English |
| DOI: | 10.1093/carcin/bgad075 |
| PUBMED: | 37856781 |
| PROVIDER: | scopus |
| PMCID: | PMC10859730 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus |
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45Chakraborty -
48Matsoukas -
197Kantoff -
69Stopsack -
11Rajanala
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