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A Case-Control Investigation of Immune Function Gene Polymorphisms and Risk of Testicular Germ Cell Tumors

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ² National Cancer Institute Core Genotyping Facility, NIH, Department of Health and Human Services, Gaithersburg, Maryland; ³ Armed Forces Institute of Pathology, Washington, District of Columbia; ⁴ U.S. Army Center for Health Promotion and Preventive Medicine; Washington, District of Columbia and ⁵ Walter Reed Army Institute of Research, Forest Glen, Maryland

Requests for reprints: Mark P. Purdue, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, EPS-8009, 6120 Executive Boulevard, Rockville, MD 20892-7234. Phone: 301-451-5036; Fax: 301-402-1819. E-mail: purduem{at}mail.nih.gov

There is reason to suspect that testicular germ cell tumor (TGCT) development may be influenced by cytokines, secreted proteins that modulate tumor immune surveillance activity as well as a variety of processes in the testis. To address this hypothesis, we conducted a case-control analysis (508 cases, 608 controls) of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5–73C>T variant was positively associated with TGCT (CT/TT versus CC: odds ratio, 1.73; 95% confidence interval, 1.01-2.95; P_trend = 0.05); additionally, haplotypes of the assessed TGFB1 SNPs (–509C>T, 327C>T, Ex1–282C>G, and Ex5–73C>T) differed in frequency between cases and controls (all TGCT, P 0.07; seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among TGCT cases versus controls of LTA 252G (P_trend = 0.08) and of the TNF variants –1042C (P_trend = 0.06), –1036T (P_trend = 0.07), and –238G (P_trend = 0.09). Analyses of haplotypes for LTA-TNF SNPs (LTA –91C>A, LTA 252A>G, TNF –863C>A, TNF –857C>T, TNF –308G>A, and –238G>A) were similarly suggestive of an association with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21). Polymorphisms in other genes were found to be associated only with seminoma (IL2) or nonseminoma (IFNGR2 and IL10). However, none of the associations remained noteworthy after applying the false discovery rate method to control for multiple testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and LTA/TNF, and possibly other immune function genes, may influence susceptibility to TGCT. (Cancer Epidemiol Biomarkers Prev 2007;16(1):77–83)

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				M. P. Purdue, B. I. Graubard, S. J. Chanock, M. V. Rubertone, R. L. Erickson, and K. A. McGlynn Genetic Variation in the Inhibin Pathway and Risk of Testicular Germ Cell Tumors Cancer Res., April 15, 2008; 68(8): 3043 - 3048. [Abstract] [Full Text] [PDF]