ABSTRACT
BACKGROUND: Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, <5 million spermatozoa/mL semen) or non-obstructive azoospermia (NOA, complete lack of spermatozoa in the ejaculate without obstructive causes). OBJECTIVES: The main objective of the present study is to analyze in the Iberian population the effect of 6 single-nucleotide polymorphisms (SNPs) previously associated with NOA in Han Chinese through genome-wide association studies (GWAS) and to establish their possible functional relevance in the development of specific SpF patterns. MATERIALS AND METHODS: We genotyped 674 Iberian infertile men (including 480 NOA and 194 SO patients) and 1058 matched unaffected controls for the GWAS-associated variants PRMT6-rs12097821, PEX10-rs2477686, CDC42BPA-rs3000811, IL17A-rs13206743, ABLIM1-rs7099208, and SOX5-rs10842262. Their association with SpF, SO, NOA, and different NOA phenotypes was evaluated by logistic regression models, and their functional relevance was defined by comprehensive interrogation of public resources. RESULTS: ABLIM1-rs7099208 was associated with SpF under both additive (OR = 0.86, p = 0.036) and dominant models (OR = 0.78, p = 0.026). The CDC42BPA-rs3000811 minor allele frequency was significantly increased in the subgroup of NOA patients showing maturation arrest (MA) of germ cells compared to the remaining NOA cases under the recessive model (OR = 4.45, p = 0.044). The PEX10-rs2477686 SNP was associated with a negative testicular sperm extraction (TESE) outcome under the additive model (OR = 1.32, p = 0.034). The analysis of functional annotations suggested that these variants affect the testis-specific expression of nearby genes and that lincRNA may play a role in SpF. CONCLUSIONS: Our data support the association of three previously reported NOA risk variants in Asians (ABLIM1-rs7099208, CDC42BPA-rs3000811, and PEX10-rs2477686) with different manifestations of SpF in Iberians of European descent, likely by influencing gene expression and lincRNA deregulation.
Subject(s)
Infertility, Male/genetics , LIM Domain Proteins/genetics , Microfilament Proteins/genetics , Myotonin-Protein Kinase/genetics , Peroxins/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Portugal , Semen Analysis , SpainABSTRACT
Synchronous colonic adenocarcinoma and well-differentiated ileal neuroendocrine tumour are infrequent and are usually incidental findings on autopsies or resected surgical specimens. Only rarely are they detected on colonoscopies or during surgery. We present a case of a synchronous caecal adenocarcinoma and well-differentiated ileal neuroendocrine tumour, undetected during colonoscopy, with carcinoid metastasis in one regional lymph node not associated with adenocarcinoma metastasis. A review of the literature shows that the association of non-synchronous second primary malignancies in patients with gastrointestinal carcinoid tumours is reported in more than 50% of cases; however, synchronous tumours are found in only 1-8%. It would appear that well-differentiated ileal neuroendocrine tumour could be a predisposing factor for the development of a second malignancy.
Subject(s)
Adenocarcinoma/pathology , Colonic Neoplasms/pathology , Ileal Neoplasms/pathology , Neoplasms, Multiple Primary/pathology , Neuroendocrine Tumors/pathology , Aged , Humans , MaleABSTRACT
El adenocarcinoma de colon primario sincrónico con un tumor neuroendocrino bien diferenciado ileal es raro y se detecta accidentalmente en autopsias o en el estudio anatomopatológico de piezas resecadas, solo ocasionalmente en la colonoscopia y excepcionalmente en el acto quirúrgico. En este artículo describimos un adenocarcinoma de ciego asociado a un tumor neuroendocrino bien diferenciado de íleon, no detectado en la colonoscopia, con metástasis ganglionares no asociadas a metástasis del adenocarcinoma. En la revisión de la literatura, la asociación de tumores primarios no carcinoides con carcinoides del tracto gastrointestinal puede representar hasta más de un 50% de forma no sincrónica, siendo la incidencia muy rara, entre 1 y 8%, en tumores sincrónicos. Parece claro que el tumor neuroendocrino bien diferenciado es un factor predisponente para desarrollar un segundo tumor primario (AU)
Synchronous colonic adenocarcinoma and well-differentiated ileal neuroendocrine tumour are infrequent and are usually incidental findings on autopsies or resected surgical specimens. Only rarely are they detected on colonoscopies or during surgery. We present a case of a synchronous caecal adenocarcinoma and well-differentiated ileal neuroendocrine tumour, undetected during colonoscopy, with carcinoid metastasis in one regional lymph node not associated with adenocarcinoma metastasis. A review of the literature shows that the association of non-synchronous second primary malignancies in patients with gastrointestinal carcinoid tumours is reported in more than 50% of cases; however, synchronous tumours are found in only 1-8%. It would appear that well-differentiated ileal neuroendocrine tumour could be a predisposing factor for the development of a second malignancy (AU)