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A Ferlin, Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
F Ganz, Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
M Pengo, Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
R Selice, Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
A Frigo, Environmental Medicine and Public Health, University of Padova, Padova, Italy
C Foresta, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, University of Padova, Padova, I-35127, Italy

Carlo Foresta, Email: carlo.foresta{at}unipd.it

Abstract

It is generally assumed that the development of testicular germ cell tumour (TGCT) is under endocrine control. In particular, an unbalanced androgen/estrogen levels and/or activity is believed to represent key events for TGCT development and progression. Furthermore, recent evidence suggested a strong genetic component for TGCT. In this study we analysed whether genetic variation in estrogen receptor genes and steroid hormone metabolism genes are associated with TGCT. We genotyped for 17 polymorphic markers in 11 genes 234 TGCT cases and 218 controls: estrogen receptor (ESR1, ESR2), CYP19A1 (aromatase), HSD17B1 and HSD17B4 dehydrogenases that convert potent androgens and estrogens to weak hormones, cytochrome P450 hydroxylating enzymes CYP1A1, CYP1A2, and CYP1B1, and the metabolic enzymes COMT, SULT1A1 and SULT1E1. We observed significant association of rs11205 in HSD17B4 with TGCT. TGCT risk was increased twofold per copy of the minor A allele at this locus (OR = 2.273, 95% CI = 1.737-2.973). Homozygous carriage of the minor A allele was associated with an over fourfold increased risk of TGCT (OR = 4.561, 95% CI = 2.615-7.955) compared with homozygous carriage of the major G allele. The risk was increased both for seminoma (OR = 5.327, 95% CI = 2.857-9.931) and for non seminoma (OR = 3.222, 95% CI = 1.471-7.059). We found for the first time association of polymorphisms in HSD17B4 gene with TGCT. Our findings expand current knowledge on the role of genetic contribution to testicular cancer susceptibility and support the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis.