Gene Polymorphism-related Individual and Interracial Differences in the Outcomes of Androgen Deprivation Therapy for Prostate Cancer

Abstract

Among patients with prostate cancer, the prognosis after androgen deprivation therapy differs significantly among individuals and among races; however, the reasons underlying these differences are poorly understood. Several single nucleotide polymorphisms in genes associated with prostate cancer progression or castration resistance might serve as the host factor that influences prognosis and, thus, accounts for these individual and racial gaps in treatment outcomes. Accordingly, single nucleotide polymorphisms associated with treatment outcomes could be used as predictive and/or prognostic biomarkers for patient stratification and to identify personalized treatment and follow-up protocols. The present review has summarized the genetic polymorphisms that have been reported to associate with androgen deprivation therapy outcomes among patients with prostate cancer and compared the allele frequencies among different ethnic groups.

Introduction

Prostate cancer is the most common non–skin cancer affecting men in Western countries,¹ and the incidence and mortality of prostate cancer are increasing in Asian countries.² Prostate cancer has been estimated to be the most commonly diagnosed cancer in men in Japan since 2015.³ Accordingly, the prevention, diagnosis, and treatment of prostate cancer are important public health issues.

Since the introduction of prostate-specific antigen (PSA) screening, for most patients, prostate cancer is diagnosed at curative early stages. However, approximately 10% of patients will have advanced disease at diagnosis. Prostate cancer is a hormone-dependent cancer; the androgen–androgen receptor (AR) axis plays a pivotal role in both disease development and progression. Thus, androgen deprivation therapy (ADT) is effective and has become the standard of care for metastatic prostate cancer. ADT can initially achieve reductions in PSA values and tumor volumes and improvement in symptoms. However, in most patients with advanced prostate cancer, ADT will eventually fail, and disease relapse will occur, resulting in castration-resistant prostate cancer (CRPC).

The prevalence and mortality of prostate cancer varies among different countries and races,⁴ and the progression and survival during ADT also differ considerably among races.⁵ Several clinical factors, such as the PSA value, cancer stage, Gleason score, and performance status, can affect survival. However, even after adjusting for disease risk, patient characteristics, and ADT method, cancer-specific survival and overall survival (OS) have been better among men treated in Japan than among those treated in the United States.6, 7 In addition, the prognosis differs significantly among patients with prostate cancer who are of the same race and have the same disease stage.

Many genes and alterations thereof are involved in prostate cancer development, progression, and treatment outcomes.8, 9 Potentially, functional polymorphisms of various genes could act as host genetic factors and modify the efficacy of ADT. The present review summarized the results of studies that have investigated the association between genetic polymorphisms and ADT efficacy among patients with prostate cancer and discussed the racial differences in the clinical outcomes of ADT.