Molecular markers in sex hormone pathway genes associated with the efficacy of androgen-deprivation therapy for prostate cancer.
Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT. A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism. We found that after adjusting for known risk factors in multivariate Cox regression models, AKR1C3 rs12529 and AR-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (P ≤ 0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (P<0.001). Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.
Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Chia-Cheng
CC
Yu
Shu-Pin
SP
Huang
Yung-Chin
YC
Lee
Chao-Yuan
CY
Huang
Chia-Chu
CC
Liu
Tzyh-Chyuan
TC
Hour
Chun-Nung
CN
Huang
Bang-Jau
BJ
You
Ta-Yuan
TY
Chang
Chun-Hsiung
CH
Huang
Bo-Ying
BY
Bao
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D005819:Genetic Markers; D012739:Gonadal Steroid Hormones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012307:Risk Factors
D000726:Androgen Antagonists; D005819:Genetic Markers; D012739:Gonadal Steroid Hormones