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Genetic variants in the 8q24 locus and risk of testicular germ cell tumors

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Abstract

Much evidence supports the premise that population genetic variation contributes significantly to the risk of testicular germ-cell tumor (TGCT). However, investigations of the association between genomic markers and TGCT susceptibility are scarce. Single nucleotide polymorphisms (SNPs) at the locus 8q24 have recently been found to be associated with prostate, colorectal and breast cancer. The US Servicemen’s testicular tumor environmental and endocrine determinants (STEED) study was used to investigate the association of 15 specific 8q24 SNPs with TGCT and its two main histologic groups of seminoma and nonseminoma. Conditional and unconditional logistic regression models, adjusted for the matching variables of year of birth, race/ethnicity and serum date, were utilized to produce odds ratios (OR) and 95% confidence intervals (95%CI). The analysis included 680 controls and 568 TGCT cases. In the TGCT analysis, no SNP was associated with risk in both heterozygotes and variant homozygotes. When stratified by histology the seminoma analysis also showed no association with the 8q24 SNPs. Conversely, the analysis of nonseminomas had three tentative associations (rs6470494, ORgenotype AG = 1.15, 95%CI: 0.86–1.54; ORgenotype GG = 1.68, 95%CI: 1.04–2.73; p for trend = 0.04) (rs13254738, ORgenotype GT = 1.04, 95%CI: 0.77–1.40; ORgenotype TT = 1.62, 95%CI: 1.06–2.49; p for trend = 0.07) (rs10505476, ORgenotype CT = 0.67, 95%CI: 0.50, 0.91; ORgenotype TT = 0.81, 95%CI: 0.47–1.39; p for trend = 0.04). There was no linkage disequilibrium between any of the 8q24 SNPs analyzed in this population. In conclusion, this study has found little evidence for an association between the reported 8q24 SNPs and TGCTs, although the findings for nonseminoma may be worth further investigation.

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Fig. 1

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Abbreviations

CI:

Confidence interval

OR:

Odds ratio

STEED:

Servicemen’s testicular tumor environmental and endocrine determinants study

TGCT:

Testicular germ cell tumor

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Acknowledgments

The investigators wish to thank Ms. Emily Steplowski of IMS, Inc. for her contributions to data management. The study was funded by the Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, 20892-7234, USA

    Michael B. Cook, Barry I. Graubard, Sabah M. Quraishi, Meredith Yeager, Stephen J. Chanock, Andrew Crenshaw, Gilles Thomas & Katherine A. McGlynn

  2. Core Genotyping Facility, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD, 21702, USA

    Meredith Yeager & Andrew Crenshaw

  3. Global Emerging Infections System, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA

    Ralph L. Erickson

  4. US Army Center for Health Promotion and Preventive Medicine, Washington, DC, 20307-500, USA

    Mark V. Rubertone

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  1. Michael B. Cook
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Cook, M.B., Graubard, B.I., Quraishi, S.M. et al. Genetic variants in the 8q24 locus and risk of testicular germ cell tumors. Hum Genet 123, 409–418 (2008). https://doi.org/10.1007/s00439-008-0491-y

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