TY - JOUR
T1 - Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations
T2 - Results from the prostate cancer prevention trial
AU - Price, Douglas K.
AU - Chau, Cindy H.
AU - Till, Cathee
AU - Goodman, Phyllis J.
AU - Leach, Robin J.
AU - Johnson-Pais, Teresa L.
AU - Hsing, Ann W.
AU - Hoque, Ashraful
AU - Parnes, Howard L.
AU - Schenk, Jeannette M.
AU - Tangen, Catherine M.
AU - Thompson, Ian M.
AU - Reichardt, Juergen K.V.
AU - Figg, William D.
N1 - Publisher Copyright:
© 2016 American Cancer Society.
PY - 2016/8
Y1 - 2016/8
N2 - BACKGROUND: Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment. METHODS: A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. RESULTS: There were significant associations of genetic polymorphisms in steroid 5a-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; Ptrend=.03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; Ptrend=.01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; Ptrend <.05) consistently and significantly altered all androgen concentrations. Several SNPs (SRD5A1 rs3822430, SRD5A2 rs2300700, CYP3A43 rs800672, and CYP19 rs700519; Ptrend <.05) were significantly associated with both circulating hormone levels and prostate cancer risk. CONCLUSIONS: Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted.
AB - BACKGROUND: Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment. METHODS: A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. RESULTS: There were significant associations of genetic polymorphisms in steroid 5a-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; Ptrend=.03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; Ptrend=.01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; Ptrend <.05) consistently and significantly altered all androgen concentrations. Several SNPs (SRD5A1 rs3822430, SRD5A2 rs2300700, CYP3A43 rs800672, and CYP19 rs700519; Ptrend <.05) were significantly associated with both circulating hormone levels and prostate cancer risk. CONCLUSIONS: Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted.
KW - Androgen
KW - Genetics
KW - Metabolism
KW - Polymorphism
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=84966668592&partnerID=8YFLogxK
U2 - 10.1002/cncr.30071
DO - 10.1002/cncr.30071
M3 - Article
C2 - 27164191
AN - SCOPUS:84966668592
SN - 0008-543X
VL - 122
SP - 2332
EP - 2340
JO - Cancer
JF - Cancer
IS - 15
ER -