Associations between polymorphisms in genes related to estrogen metabolism and function and prostate cancer risk: Results from the Prostate Cancer Prevention Trial

Li Tang, Mary E. Platek, Song Yao, Cathee Till, Phyllis J. Goodman, Catherine M. Tangen, Yue Wu, Elizabeth A. Platz, Marian L. Neuhouser, Frank Z. Stanczyk, Juergen K.V. Reichardt, Regina M. Santella, Ann Hsing, William D. Figg, Scott M. Lippman, Ian M. Thompson, Christine B. Ambrosone

Research output: Contribution to journalArticle

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Abstract

Substantial preclinical data suggest estrogen's carcinogenic role in prostate cancer development; however, epidemiological evidence based on circulating estrogen levels is largely null. Compared with circulating estrogen, the intraprostatic estrogen milieu may play a more important role in prostate carcinogenesis. Using a nested case-control design in the Prostate Cancer Prevention Trial (PCPT), we examined associations of genetic variants of genes that are involved in estrogen synthesis, metabolism and function with prostate cancer risk. A total of 25 potentially functional single nucleotide polymorphisms (SNPs) in 13 genes (PGR, ESR1, ESR2, CYP17A1, HSD17B1, CYP19A1, CYP1A1, CYP1B1, COMT, UGT1A6, UGT1A10, UGT2B7, UGT2B15) were examined in whites only. Controls (n = 1380) were frequency matched to cases on age, PCPT treatment arm, and family history (n = 1506). Logistic regression models adjusted for age and family history were used to estimate odds ratios (OR) and 95% confidence intervals (CI) separately in the placebo and finasteride arms. SNPs associated with prostate cancer risk differed by treatment arm. The associations appeared to be modified by circulating estrogen and androgen levels. CYP19A1 was the only gene harboring SNPs that were significantly associated with risk in both the placebo and finasteride arms. Haplotype analysis with all three CYP19A1 SNPs genotyped (rs700518, rs2445765, rs700519) showed that risk-allele haplotypes are associated with the increased prostate cancer risk in both arms when comparing with the non-risk allele haplotype. In conclusion, associations between SNPs in estrogen-related genes and prostate cancer risk are complex and may be modified by circulating hormone levels and finasteride treatment.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalCarcinogenesis
Volume39
Issue number2
DOIs
StatePublished - Feb 1 2018

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Prostatic Neoplasms
Estrogens
Single Nucleotide Polymorphism
Finasteride
Genes
Haplotypes
Logistic Models
Alleles
Placebos
Cytochrome P-450 CYP1A1
Androgens
Prostate
Carcinogenesis
Therapeutics
Odds Ratio
Hormones
Confidence Intervals

ASJC Scopus subject areas

  • Cancer Research

Cite this

Associations between polymorphisms in genes related to estrogen metabolism and function and prostate cancer risk : Results from the Prostate Cancer Prevention Trial. / Tang, Li; Platek, Mary E.; Yao, Song; Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.; Wu, Yue; Platz, Elizabeth A.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Reichardt, Juergen K.V.; Santella, Regina M.; Hsing, Ann; Figg, William D.; Lippman, Scott M.; Thompson, Ian M.; Ambrosone, Christine B.

In: Carcinogenesis, Vol. 39, No. 2, 01.02.2018, p. 125-133.

Research output: Contribution to journalArticle

Tang, L, Platek, ME, Yao, S, Till, C, Goodman, PJ, Tangen, CM, Wu, Y, Platz, EA, Neuhouser, ML, Stanczyk, FZ, Reichardt, JKV, Santella, RM, Hsing, A, Figg, WD, Lippman, SM, Thompson, IM & Ambrosone, CB 2018, 'Associations between polymorphisms in genes related to estrogen metabolism and function and prostate cancer risk: Results from the Prostate Cancer Prevention Trial', Carcinogenesis, vol. 39, no. 2, pp. 125-133. https://doi.org/10.1093/carcin/bgx144
Tang, Li ; Platek, Mary E. ; Yao, Song ; Till, Cathee ; Goodman, Phyllis J. ; Tangen, Catherine M. ; Wu, Yue ; Platz, Elizabeth A. ; Neuhouser, Marian L. ; Stanczyk, Frank Z. ; Reichardt, Juergen K.V. ; Santella, Regina M. ; Hsing, Ann ; Figg, William D. ; Lippman, Scott M. ; Thompson, Ian M. ; Ambrosone, Christine B. / Associations between polymorphisms in genes related to estrogen metabolism and function and prostate cancer risk : Results from the Prostate Cancer Prevention Trial. In: Carcinogenesis. 2018 ; Vol. 39, No. 2. pp. 125-133.
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abstract = "Substantial preclinical data suggest estrogen's carcinogenic role in prostate cancer development; however, epidemiological evidence based on circulating estrogen levels is largely null. Compared with circulating estrogen, the intraprostatic estrogen milieu may play a more important role in prostate carcinogenesis. Using a nested case-control design in the Prostate Cancer Prevention Trial (PCPT), we examined associations of genetic variants of genes that are involved in estrogen synthesis, metabolism and function with prostate cancer risk. A total of 25 potentially functional single nucleotide polymorphisms (SNPs) in 13 genes (PGR, ESR1, ESR2, CYP17A1, HSD17B1, CYP19A1, CYP1A1, CYP1B1, COMT, UGT1A6, UGT1A10, UGT2B7, UGT2B15) were examined in whites only. Controls (n = 1380) were frequency matched to cases on age, PCPT treatment arm, and family history (n = 1506). Logistic regression models adjusted for age and family history were used to estimate odds ratios (OR) and 95{\%} confidence intervals (CI) separately in the placebo and finasteride arms. SNPs associated with prostate cancer risk differed by treatment arm. The associations appeared to be modified by circulating estrogen and androgen levels. CYP19A1 was the only gene harboring SNPs that were significantly associated with risk in both the placebo and finasteride arms. Haplotype analysis with all three CYP19A1 SNPs genotyped (rs700518, rs2445765, rs700519) showed that risk-allele haplotypes are associated with the increased prostate cancer risk in both arms when comparing with the non-risk allele haplotype. In conclusion, associations between SNPs in estrogen-related genes and prostate cancer risk are complex and may be modified by circulating hormone levels and finasteride treatment.",
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AU - Yao, Song

AU - Till, Cathee

AU - Goodman, Phyllis J.

AU - Tangen, Catherine M.

AU - Wu, Yue

AU - Platz, Elizabeth A.

AU - Neuhouser, Marian L.

AU - Stanczyk, Frank Z.

AU - Reichardt, Juergen K.V.

AU - Santella, Regina M.

AU - Hsing, Ann

AU - Figg, William D.

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N2 - Substantial preclinical data suggest estrogen's carcinogenic role in prostate cancer development; however, epidemiological evidence based on circulating estrogen levels is largely null. Compared with circulating estrogen, the intraprostatic estrogen milieu may play a more important role in prostate carcinogenesis. Using a nested case-control design in the Prostate Cancer Prevention Trial (PCPT), we examined associations of genetic variants of genes that are involved in estrogen synthesis, metabolism and function with prostate cancer risk. A total of 25 potentially functional single nucleotide polymorphisms (SNPs) in 13 genes (PGR, ESR1, ESR2, CYP17A1, HSD17B1, CYP19A1, CYP1A1, CYP1B1, COMT, UGT1A6, UGT1A10, UGT2B7, UGT2B15) were examined in whites only. Controls (n = 1380) were frequency matched to cases on age, PCPT treatment arm, and family history (n = 1506). Logistic regression models adjusted for age and family history were used to estimate odds ratios (OR) and 95% confidence intervals (CI) separately in the placebo and finasteride arms. SNPs associated with prostate cancer risk differed by treatment arm. The associations appeared to be modified by circulating estrogen and androgen levels. CYP19A1 was the only gene harboring SNPs that were significantly associated with risk in both the placebo and finasteride arms. Haplotype analysis with all three CYP19A1 SNPs genotyped (rs700518, rs2445765, rs700519) showed that risk-allele haplotypes are associated with the increased prostate cancer risk in both arms when comparing with the non-risk allele haplotype. In conclusion, associations between SNPs in estrogen-related genes and prostate cancer risk are complex and may be modified by circulating hormone levels and finasteride treatment.

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