title: A case-control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors.
abstract: 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.
authors.affiliation: 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, USA. purduem@mail.nih.gov
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Sesterhenn
authors.forename: Mark V
authors.initials: MV
authors.lastname: Rubertone
authors.forename: R Loren
authors.initials: RL
authors.lastname: Erickson
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McGlynn
mesh_terms: D016022:Case-Control Studies; D006801:Humans; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D018239:Seminoma / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D013736:Testicular Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000235:genetics; D014481:United States / Q000453:epidemiology; D044465:White People
chemical_list: D008233:Lymphotoxin-alpha; D053773:Transforming Growth Factor beta1