Genetic variants of GPER/GPR30, a novel estrogen-related G protein receptor, are associated with human seminoma.
Testicular germ cell tumors (TGCTs) are the most common solid cancers in young men, with an increasing incidence over several years. However, their pathogenesis remains a matter of debate. Some epidemiological data suggest the involvement of both environmental and genetic factors. We reported two distinct effects of estrogens and/or xeno-estrogens on in vitro human seminoma-derived cells proliferation: (1) an antiproliferative effect via a classical estrogen receptor beta-dependent pathway, and (2) a promotive effect via a non-classical membrane G-protein-coupled receptor, GPR30/GPER, which is only overexpressed in seminomas, the most common TGCT. In order to explain this overexpression, we investigated the possible association of polymorphisms in the GPER gene by using allele-specific tetra-primer polymerase chain reaction performed on tissue samples from 150 paraffin-embedded TGCT specimens (131 seminomas, 19 non seminomas). Compared to control population, loss of homozygous ancestral genotype GG in two polymorphisms located in the promoter region of GPER (rs3808350 and rs3808351) was more frequent in seminomas but not in non-seminomas (respectively, OR = 1.960 (1.172-3.277) and 7.000 (2.747-17.840); p < 0.01). These polymorphisms may explain GPER overexpression and represent a genetic factor of susceptibility supporting the contribution of environmental GPER ligands in testicular carcinogenesis.
Institut National de la Santé et de la Recherche Médicale (INSERM) UMR U1065/UNS, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 5, Environnement, Reproduction et Cancers Hormono-Dépendants, Nice 06204, France. chevalier.n@chu-nice.fr.
Nicolas
N
Chevalier
Institut National de la Santé et de la Recherche Médicale (INSERM) UMR U1065/UNS, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 5, Environnement, Reproduction et Cancers Hormono-Dépendants, Nice 06204, France. paul@unice.fr.
Rachel
R
Paul-Bellon
Foch, Laboratoire d'Anatomie Pathologique, Suresnes 92151, France. anapath@hopital-foch.org.
Philippe
P
Camparo
Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur, Nice 06000, France. michiels.jf@chu-nice.fr.
Jean-François
JF
Michiels
Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet, Service d'Urologie, Nice 06202, France. chevallier.d@chu-nice.fr.
Daniel
D
Chevallier
Institut National de la Santé et de la Recherche Médicale (INSERM) UMR U1065/UNS, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 5, Environnement, Reproduction et Cancers Hormono-Dépendants, Nice 06204, France. fenichel.p@chu-nice.fr.
Patrick
P
Fénichel
D000328:Adult; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018239:Seminoma / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism
D004967:Estrogens; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled