Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer

Julie M Cunningham, Scott J. Hebbring, Shannon K. McDonnell, Mine Cicek, G. Bryce Christensen, Liang Wang, Steven J. Jacobsen, James R Cerhan, Michael L. Blute, Daniel J Schaid, Stephen N Thibodeau

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Abstract

Previous studies suggest that enzymes involved in the androgen metabolic pathway are susceptibility factors for prostate cancer. Estrogen metabolites functioning as genotoxins have also been proposed as risk factors. In this study, we systematically tested the hypothesis that common genetic variations for those enzymes involved in the androgen and estrogen metabolic pathways increase risk for sporadic and familial prostate cancer. From these two pathways, 46 polymorphisms (34 single nucleotide polymorphisms, 10 short tandem repeat polymorphisms, and 2 null alleles) in 25 genes were tested for possible associations. Those genes tested included PRL, LHB, CYP11A1, HSD3B1, HSD3B2, HSD17B2, CYP17, SRD5A2, AKR1C3, UGT2B15, AR, SHBG, and KLK3 from the androgen pathway and CYP19, HSD17B1, CYP1A1, CYP1A2, CYP1B1, COMT, GSTP1, GSTT1, GSTM1, NQO1, ESR1, and ESR2 from the estrogen pathway. A case-control study design was used with two sets of cases: familial cases with a strong prostate cancer family history (n = 438 from 178 families) and sporadic cases with a negative prostate cancer family history (n = 499). The controls (n = 493) were derived from a population-based collection. Our results provide suggestive findings for an association with either familial or sporadic prostate cancer with polymorphisms in four genes: AKR1C3, HSD17B1, NQO1, and GSTT1. Additional suggestive findings for an association with clinical variables (disease stage, grade, and/or node status) were observed for single nucleotide polymorphisms in eight genes: HSD3B2, SRD5A2, SHBG, ESR1, CYP1A1, CYP1B1, GSTT1, and NQO1. However, none of the findings were statistically significant after appropriate corrections for multiple comparisons. Given that the point estimates for the odds ratio for each of these polymorphisms are <2.0, much larger sample sizes will be required for confirmation.

Original languageEnglish (US)
Pages (from-to)969-978
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number5
DOIs
StatePublished - May 2007

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Metabolic Networks and Pathways
Androgens
Prostatic Neoplasms
Estrogens
Cytochrome P-450 CYP1A1
Genes
Single Nucleotide Polymorphism
Cholesterol Side-Chain Cleavage Enzyme
Steroid 17-alpha-Hydroxylase
Cytochrome P-450 CYP1A2
Aromatase
Mutagens
Enzymes
Microsatellite Repeats
Sample Size
Case-Control Studies
Alleles
Odds Ratio
Familial Prostate cancer
Population

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer. / Cunningham, Julie M; Hebbring, Scott J.; McDonnell, Shannon K.; Cicek, Mine; Christensen, G. Bryce; Wang, Liang; Jacobsen, Steven J.; Cerhan, James R; Blute, Michael L.; Schaid, Daniel J; Thibodeau, Stephen N.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 16, No. 5, 05.2007, p. 969-978.

Research output: Contribution to journalArticle

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AU - Christensen, G. Bryce

AU - Wang, Liang

AU - Jacobsen, Steven J.

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