Analysis of single nucleotide polymorphisms of FSH receptor gene suggests association with testicular cancer susceptibility.
The development of testicular germ cell tumour (TGCT) is believed to be under endocrine control but definitive proofs are lacking. Follicle stimulating hormone (FSH) levels are increased in numerous conditions associated with increased risk of TGCT and single nucleotide polymorphisms (SNPs) in the FSH receptor (FSHR) gene influence the sensitivity of the receptor to FSH. However, a possible effect of FSH on testicular carcinogenesis has never been explored. In order to analyse the possible association of FSHR polymorphisms with TGCT, we studied 188 TGTC cases and 152 controls for 12 FSHR SNPs. Only four SNPs were found to be informative, represented by two polymorphisms in exon 10 (Ala307Thr and Ser680Asn), and two polymorphisms in the promoter region (-114 T/C and -29 G/A). Differences in haplotype distribution were seen between TGCT cases and controls. In particular for non-seminoma, the Ala307/Ser680 allele lowers the risk of the disease, alone (P=0.014, relative risk 0.73; 95% confidence interval 0.57-0.92), or in combination with the -29 G allele and/or the -114 T allele. This study suggests for the first time that FSHR gene polymorphisms modulate susceptibility to TGCT. The variants with higher activity of the FSHR are associated with higher risk, suggesting a role for FSH in the carcinogenesis of this tumour.
Ferlin
Alberto
A
Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, University of Padova, Via Gabelli 63, 35121 Padova, Italy.
Pengo
Manuel
M
Selice
Riccardo
R
Salmaso
Luigi
L
Garolla
Andrea
A
Foresta
Carlo
C
D000328:Adult; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011962:Receptors, FSH / Q000235:genetics*; D012307:Risk Factors; D018239:Seminoma / Q000453:epidemiology / Q000235:genetics*; D013736:Testicular Neoplasms / Q000453:epidemiology / Q000235:genetics*
D011962:Receptors, FSH