Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes

V. M. Chia, Y. Li, S. M. Quraishi, B. I. Graubard, J. D. Figueroa, J. P. Weber, S. J. Chanock, M. V. Rubertone, R. L. Erickson, K. A. McGlynn

Research output: Contribution to journalArticle

Abstract

It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′-dichlorodiphenyldichloroethylene, chlordane-related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01-3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p-interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45-55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions <0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.

Original languageEnglish (US)
Pages (from-to)588-596
Number of pages9
JournalInternational Journal of Andrology
Volume33
Issue number4
DOIs
StatePublished - Aug 2010
Externally publishedYes

Fingerprint

Endocrine Disruptors
Hormones
Polychlorinated Biphenyls
Genes
Chlordan
Cytochrome P-450 CYP1A1
Alleles
Genotype
Logistic Models
Odds Ratio
Confidence Intervals
Dichlorodiphenyl Dichloroethylene
Testicular Neoplasms
Testicular Germ Cell Tumor
Enzymes

Keywords

  • hormone-metabolizing genes
  • persistent organochlorine pesticides
  • polychlorinated biphenyls
  • testicular germ cell tumours

ASJC Scopus subject areas

  • Urology
  • Reproductive Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chia, V. M., Li, Y., Quraishi, S. M., Graubard, B. I., Figueroa, J. D., Weber, J. P., ... McGlynn, K. A. (2010). Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes. International Journal of Andrology, 33(4), 588-596. https://doi.org/10.1111/j.1365-2605.2009.00975.x

Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes. / Chia, V. M.; Li, Y.; Quraishi, S. M.; Graubard, B. I.; Figueroa, J. D.; Weber, J. P.; Chanock, S. J.; Rubertone, M. V.; Erickson, R. L.; McGlynn, K. A.

In: International Journal of Andrology, Vol. 33, No. 4, 08.2010, p. 588-596.

Research output: Contribution to journalArticle

Chia, VM, Li, Y, Quraishi, SM, Graubard, BI, Figueroa, JD, Weber, JP, Chanock, SJ, Rubertone, MV, Erickson, RL & McGlynn, KA 2010, 'Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes', International Journal of Andrology, vol. 33, no. 4, pp. 588-596. https://doi.org/10.1111/j.1365-2605.2009.00975.x
Chia, V. M. ; Li, Y. ; Quraishi, S. M. ; Graubard, B. I. ; Figueroa, J. D. ; Weber, J. P. ; Chanock, S. J. ; Rubertone, M. V. ; Erickson, R. L. ; McGlynn, K. A. / Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes. In: International Journal of Andrology. 2010 ; Vol. 33, No. 4. pp. 588-596.
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