SLCO2B1 Linked to Poorer Survival in ADT-Treated Prostate Cancer

Men with prostate cancer who carry certain variants in the SLCO2B1 gene, which helps cells internalize androgens, have shorter time to progression and overall survival, according to the results of a new study published in the Journal of Clinical Oncology.

Three germline variants of the SLCO2B1 gene, exonic single nucleotide polymorphisms (SNP) rs12422149 and intronic SNPs rs1789693 and rs1077858, were examined for their association with time to disease progression and overall survival in a cohort of 1,094 men diagnosed with prostate cancer who had been treated with androgen deprivation therapy (ADT).

Philip W. Kantoff, MD, chairman of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, and colleagues previously found that different alleles of the SLCO2B1 gene can negatively impact time to progression for prostate cancer patients. The median decrease in time to progression for patients harboring one of the three identified risk alleles was 10 months.

The researchers analyzed outcomes in an initial cohort of 478 patients and a validation cohort of 616 patients, of which 66% had progressed on ADT. With a median follow-up of 6.5 years, the median overall survival in the combined cohort was 6.5 years.

The rs12422149 allele was associated with a shorter time to progression (hazard ratio [HR]; 1.33; P = .003) among patients treated with ADT; no association between the allele and overall survival was found. This discrepancy may be due to other genetic factors influencing androgen metabolism.

Another allele, rs1077858, was found to have borderline significance (P = .075) in influencing time to progression. Patients with a certain variant of the allele had a decreased median overall survival from 6.7 to 5.2 years (P = .009).

The third allele, rs1789693, did not appear linked to time to progression in the new analysis. There was also no association between this allele and overall survival from ADT initiation, but on multivariable analysis patients with certain variants had longer overall survival than did those without (P = .044).

In prostate cell lines, increasing expression of SLCO2B1 increased androgen uptake into the cells.

The results of the study suggest that the SLCO2B1 gene, and potentially others, influence the way androgens are transported into prostate cells, at least partially accounting for the variable efficacy seen among prostate cancer patients treated with ADT.

“These findings suggest that SLCO2B1 variants are prognostic markers of durability of response to ADT. Further, SLCO2B1 may serve as a target for novel agents and strategies,” concluded the study authors.