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

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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.

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Acknowledgments

The authors wish to thank Emily Steplowski of IMS for her contributions to data management and Sabah Quraishi for her contributions to data analysis. In addition, Jonine Figueroa would like to thank Victoria Chia and Michael Cook for discussions about data presentation and the NCI Cancer Prevention Fellowship program for their support. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

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Authors and Affiliations

  1. Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Jonine D. Figueroa, Barry I. Graubard, Stephen Chanock & Katherine A. McGlynn

  2. Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Jonine D. Figueroa

  3. Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA

    Lori C. Sakoda

  4. Department of Health and Human Services, Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Bethesda, MD, USA

    Stephen Chanock

  5. U.S. Army Center for Health Promotion and Preventive Medicine, Silver Spring, MD, USA

    Mark V. Rubertone

  6. Global Emerging Infections System, Walter Reed Army Institute of Research, Silver Spring, MD, USA

    R. Loren Erickson

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  1. Jonine D. Figueroa
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Figueroa, J.D., Sakoda, L.C., Graubard, B.I. et al. Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors. Cancer Causes Control 19, 917–929 (2008). https://doi.org/10.1007/s10552-008-9153-6

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