Genome-wide assessment of the association of rare and common copy number variations to testicular germ cell cancer.

Testicular germ cell cancer (TGCC) is one of the most heritable forms of cancer. Previous genome-wide association studies have focused on single nucleotide polymorphisms (SNPs), largely ignoring the influence of copy number variants (CNVs). Here we present a genome-wide study of copy number variation on a cohort of 212 cases and 437 controls from Denmark, which was genotyped at ~1.8 million markers, half of which were non-polymorphic copy number markers. No association of common variants were found, whereas analysis of rare variants (present in less than 1% of the samples) initially indicated a single gene with significantly higher accumulation of rare CNVs in cases as compared to controls, at the gene PTPN1 (P=3.8*10-2, 0.9% of cases and 0% of controls). However, the CNV could not be verified by qPCR in the affected samples. The CNV calling of the array data was validated by sequencing of the GSTM1 gene, which showed that the CNV frequency was in complete agreement between the two platforms. This study therefore disconfirms the hypothesis that there exists a single CNV locus with a major effect size that predisposes to TGCC. Genome-wide pathway association analysis indicated a weak association of rare CNVs related to cell migration (FDR=0.021, 1.8% of cases and 1.1% of controls). Dysregulation during migration of primordial germ cells has previously been suspected to be a part of TGCC development and this set of multiple rare variants may thereby have a minor contribution to an increased susceptibility of TGCCs

Bone mineral density is preserved in men with idiopathic infertility

Background:Lower semen quality is associated with increased mortality and morbidity, which may include osteoporosis.Objective:To assess whether infertile men have a lower bone mineral density (BMD) compared with fertile men at the time of fer-tility workup.Methods:A total of 146 men from infertile couples with unexplained impaired semen quality, characterized by sperm concentra-tion<20 million/mL, progressive motility<50% or<12% morphologically normal spermatozoa. Men with infertility due to agenetic etiology or a condition that could cause testicular damage were excluded. A total of 271 men from couples with an ongoingnaturally conceived pregnancy served as a control group. Lumbar, femoral, and total body BMD were measured by dual X-rayabsorptiometry.Results:Infertile men had similar BMD compared with fertile men (Beta coefficient (g/cm2) and 95% confidence interval for thedifference between the two groups: 0.02 ( 0.05; 0.01) for lumbar BMD, 0.02 ( 0.05; 0.01) for femoral neck BMD, 0.01 ( 0.04;0.02) for total femur BMD, and 0.01 ( 0.03; 0.01) for total body BMD). Semen parameters were not associated with BMD measure-ments. Furthermore, BMD did not differ between infertile men with the lowest semen quality vs. infertile men with better semenquality nor between infertile men with low testosterone vs. fertile men with normal testosterone levels.Conclusion:Bone mineral density is preserved in men with unexplained infertility at the time of fertility workup.status: Published onlin