SLCO2B1 Gene Polymorphisms Associated with Prostate Cancer Progression, Survival Following ADT

ORLANDO—Variants of the solute carrier organic anion transporter family gene SLCO2B1 are associated with time to tumor progression (TTP) and overall survival (OS) among patients undergoing androgen deprivation therapy (ADT) for prostate cancer, according to a validation study (Abstract 137) presented during the 2015 Genitourinary Cancers Symposium.¹

The authors also presented evidence that statins may modulate the TTP findings.

“SLCO2B1 is an important mediator of androgen metabolism,” said lead author Philip W. Kantoff, MD, of the Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, in Boston, MA. “Germline variants within SLCO2B1 modulate function or expression of SLCO2B1, subsequently affecting the uptake of androgen precursors and affecting TTP or OS in [patients with] prostate cancer.”

Kantoff noted that in vitro, statins compete with DHEAS for SLCOB1 transport, potentially decreasing a tumor’s available androgen pool. “Statin use may improve TTP on ADT. We need to be more cognizant of the complex interactions of non-cancer related medications and our cancer therapies.”

A previous analysis had found that genotypes at three single-nucleotide polymorphisms (SNPs; rs12422149, rs1789693, rs1077858) within the gene SLCO2B1 were associated with TTP (as defined by PSA levels) among patients undergoing ADT, the coauthors noted.

There “seemed to be an additive effect of the SNPs,” implying the involvement of independent biological mechanisms, Dr. Kantoff noted.

The study team externally validated the association between SLCO2B1 variants and TTP in an independent validation cohort of patients undergoing ADT (616 patients), and analyzed these genetic variants’ association with OS in both the original study cohort (538 patients) and the validation cohort.

At a median follow-up of 4.2 years, 408 of the 616 validation-cohort patients (66%) had progressed on ADT.

TTP and OS were both associated with SLCO2B1 genotype. GG risk allele genotype had a median TTP of 17.7 months compared with 27.5 months TTP for AA/AG genotypes (P=0.0019).

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The GG risk allele genotype was associated with a median OS of 5.2 months compared with 6.7 months for those with AA/AG genotypes (P=0.0091).

The TTP and OS associations with genotype remained statistically significant in multivariate analysis adjusting for Gleason score, type of primary therapy, metastatic disease status, and PSA at initiation of ADT, Dr. Kantoff noted.

At ADT initiation, 283 patients (30.6% of patients eligible for analysis) were taking a statin, of whom 93% remained on a statin at last follow-up. Median TTP on ADT was significantly longer among patients who were taking statins (27.5 vs. 17.4 months; P=0.0005), Dr. Kantoff reported.

“The association remained statistically significant after adjusting for the predefined prognostic clinical factors,” he noted.

Reference

1. Kantoff PW, Wang X, Wanling Xie, et al. Genetic variants of the organic anion transporter SLCO2B1 as pharmacogenomic determinants of response to androgen deprivation therapy (ADT) for prostate cancer. 2015 Genitourinary Cancers Symposium. Abstract 137.