Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors

Jonine D Figueroa, Lori C Sakoda, Barry I Graubard, Stephen Chanock, Mark V Rubertone, R Loren Erickson, Katherine A McGlynn

Research output: Contribution to journalArticlepeer-review

Abstract

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma.

Original languageEnglish
Pages (from-to)917-29
Number of pages13
JournalCancer Causes & Control
Volume19
Issue number9
DOIs
Publication statusPublished - Nov 2008

Keywords

  • 17-Hydroxysteroid Dehydrogenases
  • Adult
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1
  • Estradiol Dehydrogenases
  • Genetic Predisposition to Disease
  • Humans
  • Hydro-Lyases
  • Introns
  • Male
  • Neoplasms, Germ Cell and Embryonal
  • Odds Ratio
  • Peroxisomal Multifunctional Protein-2
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Steroid 17-alpha-Hydroxylase
  • Testicular Neoplasms
  • Young Adult

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