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Meta-Analysis
. 2024 Feb 12;45(1-2):35-44.
doi: 10.1093/carcin/bgad075.

SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis

Sai Harisha Rajanala  1 , Anna Plym  2   3   4 , Jane B Vaselkiv  2 , Ericka M Ebot  2 , Konstantina Matsoukas  5 , Zhike Lin  2 , Goutam Chakraborty  1   6 , Sarah C Markt  7 , Kathryn L Penney  2   8 , Gwo-Shu M Lee  9 , Lorelei A Mucci  2 , Philip W Kantoff  1   10 , Konrad H Stopsack  1   2   11
Affiliations
Meta-Analysis

SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis

Sai Harisha Rajanala et al. Carcinogenesis. .

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.

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Conflict of interest statement

K.L.P. and L.A.M. received research grants/funding from Janssen. G.C. has served as a scientific consultant for GuidePoint and received consultation fees. S.C.M. reports employment and stock ownership with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. L.A.M. received grants/funding from AstraZeneca, has consulted for Bayer Pharmaceuticals, and is on the scientific advisory board for and has equity in Convergent Therapeutics. L.A.M. and K.H.S. received research funding, to Harvard University, from Veracyte. P.W.K. has investment interest in Convergent Therapeutics, Context Therapeutics LLC, and ESSA Pharma. He is a company board member for Convergent Therapeutics, Context Therapeutics, and Essa Pharma. He is a consultant/scientific advisory board member for ImmunisAI and PrognomIQ.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Meta-analysis for prostate cancer outcomes (clinical or biochemical progression, metastases, or death from prostate cancer). On the left-hand side, study name (year) and total event counts/total participants are shown. On the right-hand side, hazard ratio and 95% confidence interval are shown. NA, not available.
See this image and copyright information in PMC

References

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