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Testicular cancer (TC) is the most common cancer in males aged 20-40 years, with a worldwide incidence of 7.5 per 100,000, but the rates vary considerably between countries and ethnic groups and there is evidence also for an increasing incidence in last decades. About 95% of all TCs are represented by testicular germ cell tumors (TGCTs), which include seminoma and non-seminoma histological types. It is generally assumed that the development of TGCT is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested genetic association of TGCT with variations in genes involved in hypothalamic-pituitary-testicular axis and steroidogenic enzymes. This recent evidence expands the current knowledge on the role of genetic contribution in testicular cancer susceptibility, and supports the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis. Therefore, hormonal carcinogenesis is an important and controversial area of current research in TGCT, and further attention is given to genetic factors influencing hormone-related cancer risk. The genetic component to TGCT is in general strong. In fact, although environmental factors clearly contribute to TGCT development (and probably to its increasing incidence in some geographical areas), the proportion of TGCT susceptibility accounted for by the genetic effects is estimated at 25%. TGCT has high familial risks compared with most other cancer types that are generally no more than two-fold: brothers of individuals with TGCT have an 8- to 12-fold increased risk of disease, and sons of affected individuals have a 4- to 6-fold increased risk. Despite this strong familial relative risk, early results from linkage studies identified a limited relationship with genetic factors, suggesting that TGCT is a genetically complex trait. However, more recently, four genome-wide association studies (GWAS) from the UK and USA have reported association of TGCTs with six new loci (KITLG, SPRY4, BAK1, DMRT1, TERT, and ATF7IP). The strongest association for TGCT susceptibility was found for SNPs in KITLG (ligand for the membrane-bound receptor tyrosine kinase KIT) gene with a greater than 2.5-fold increased risk of disease per major allele, which is the highest reported for any cancer to date. These studies are being now replicated by other researches and attention is given to the relationship between these genetic variations, TGCT risk and frequently associated anomalies of the reproductive tract, such as cryptorchidism and infertility. Finally, over the past few decades, TCGT research has focused also on external environmental causes acting mainly as endocrine disrupters of androgen and oestrogen pathways, even during the foetal development of the testis. It is well known that the testicular dysgenesis syndrome (TDS) hypothesis, proposed ten years ago, suggests that disturbed testicular development in fetal life may result in one or more of four disorders postnatally, named cryptorchidism, hypospadias, poor semen quality, and TGCT. These four disorders are therefore considered as one clinical entity and are linked together by epidemiological and pathophysiological relations. The relative contribution of genetics and environment in TGCT development, and the interactions between endocrine disruptors and variations in genes involved in hormonal carcinogenesis is therefore another interesting area of research.

Germ cell tumor --- KITLG --- cancer genetics --- testis cancer --- Cryptorchidism --- Endocrine Disruptors --- Germ cell tumor --- KITLG --- cancer genetics --- testis cancer --- Cryptorchidism --- Endocrine Disruptors

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Testicular cancer (TC) is the most common cancer in males aged 20-40 years, with a worldwide incidence of 7.5 per 100,000, but the rates vary considerably between countries and ethnic groups and there is evidence also for an increasing incidence in last decades. About 95% of all TCs are represented by testicular germ cell tumors (TGCTs), which include seminoma and non-seminoma histological types. It is generally assumed that the development of TGCT is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested genetic association of TGCT with variations in genes involved in hypothalamic-pituitary-testicular axis and steroidogenic enzymes. This recent evidence expands the current knowledge on the role of genetic contribution in testicular cancer susceptibility, and supports the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis. Therefore, hormonal carcinogenesis is an important and controversial area of current research in TGCT, and further attention is given to genetic factors influencing hormone-related cancer risk. The genetic component to TGCT is in general strong. In fact, although environmental factors clearly contribute to TGCT development (and probably to its increasing incidence in some geographical areas), the proportion of TGCT susceptibility accounted for by the genetic effects is estimated at 25%. TGCT has high familial risks compared with most other cancer types that are generally no more than two-fold: brothers of individuals with TGCT have an 8- to 12-fold increased risk of disease, and sons of affected individuals have a 4- to 6-fold increased risk. Despite this strong familial relative risk, early results from linkage studies identified a limited relationship with genetic factors, suggesting that TGCT is a genetically complex trait. However, more recently, four genome-wide association studies (GWAS) from the UK and USA have reported association of TGCTs with six new loci (KITLG, SPRY4, BAK1, DMRT1, TERT, and ATF7IP). The strongest association for TGCT susceptibility was found for SNPs in KITLG (ligand for the membrane-bound receptor tyrosine kinase KIT) gene with a greater than 2.5-fold increased risk of disease per major allele, which is the highest reported for any cancer to date. These studies are being now replicated by other researches and attention is given to the relationship between these genetic variations, TGCT risk and frequently associated anomalies of the reproductive tract, such as cryptorchidism and infertility. Finally, over the past few decades, TCGT research has focused also on external environmental causes acting mainly as endocrine disrupters of androgen and oestrogen pathways, even during the foetal development of the testis. It is well known that the testicular dysgenesis syndrome (TDS) hypothesis, proposed ten years ago, suggests that disturbed testicular development in fetal life may result in one or more of four disorders postnatally, named cryptorchidism, hypospadias, poor semen quality, and TGCT. These four disorders are therefore considered as one clinical entity and are linked together by epidemiological and pathophysiological relations. The relative contribution of genetics and environment in TGCT development, and the interactions between endocrine disruptors and variations in genes involved in hormonal carcinogenesis is therefore another interesting area of research.

Germ cell tumor --- KITLG --- cancer genetics --- testis cancer --- Cryptorchidism --- Endocrine Disruptors

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Nervous system --- Peripheral Nervous System Diseases --- Central Nervous System Neoplasms --- Nervous System Neoplasms --- Brain Diseases --- Skull Neoplasms --- Neuroectodermal Tumors --- Spinal Cord Diseases --- Neoplasms, Glandular and Epithelial --- Bone Neoplasms --- Neoplasms by Site --- Neoplasms by Histologic Type --- Central Nervous System Diseases --- Neuromuscular Diseases --- Nervous System Diseases --- Neoplasms, Nerve Tissue --- Neoplasms, Germ Cell and Embryonal --- Neoplasms --- Bone Diseases --- Diseases --- Musculoskeletal Diseases --- Brain Neoplasms --- Peripheral Nervous System Neoplasms --- Skull Base Neoplasms --- Spinal Cord Neoplasms --- Neoplasms, Neuroepithelial --- Medicine --- Health & Biological Sciences --- Oncology --- Tumors --- Neuroepithelial Neoplasms --- Neuroepithelial Tumors --- Astroblastoma --- Ependymoastrocytoma --- Gliomatosis Cerebri --- Spongioblastoma, Polar --- Astroblastomas --- Ependymoastrocytomas --- Neoplasm, Neuroepithelial --- Neuroepithelial Neoplasm --- Neuroepithelial Tumor --- Polar Spongioblastoma --- Polar Spongioblastomas --- Spongioblastomas, Polar --- Tumor, Neuroepithelial --- Tumors, Neuroepithelial --- Intramedullary Spinal Cord Neoplasms, Primary --- Neoplasms, Spinal Cord --- Primary Intramedullary Spinal Cord Neoplasms --- Primary Spinal Cord Neoplasms, Intramedullary --- Spinal Cord Neoplasms, Benign --- Spinal Cord Neoplasms, Intradural-Extramedullary --- Spinal Cord Neoplasms, Intramedullary --- Spinal Cord Neoplasms, Malignant --- Spinal Cord Neoplasms, Primary Intramedullary --- Tumors, Spinal Cord --- Intradural-Extramedullary Spinal Cord Neoplasms --- Intramedullary Spinal Cord Neoplasms --- Intradural Extramedullary Spinal Cord Neoplasms --- Neoplasm, Spinal Cord --- Spinal Cord Neoplasm --- Spinal Cord Neoplasms, Intradural Extramedullary --- Spinal Cord Tumor --- Spinal Cord Tumors --- Tumor, Spinal Cord --- Neoplasms, Skull Base --- Neoplasm, Skull Base --- Skull Base Neoplasm --- Peripheral Nerve Neoplasms --- Peripheral Nerve Neoplasms, Benign --- Peripheral Nerve Neoplasms, Malignant --- Peripheral Nerve Neoplastic Infiltration --- Peripheral Nerve Tumors --- Peripheral Nervous System Benign Neoplasms --- Peripheral Nervous System Malignant Neoplasms --- Neoplasm, Peripheral Nerve --- Neoplasms, Peripheral Nerve --- Nerve Neoplasm, Peripheral --- Nerve Neoplasms, Peripheral --- Nerve Tumor, Peripheral --- Nerve Tumors, Peripheral --- Peripheral Nerve Neoplasm --- Peripheral Nerve Tumor --- Tumor, Peripheral Nerve --- Tumors, Peripheral Nerve --- Benign Neoplasms, Brain --- Brain Neoplasm, Primary --- Brain Neoplasms, Benign --- Brain Neoplasms, Malignant --- Brain Neoplasms, Malignant, Primary --- Brain Neoplasms, Primary Malignant --- Brain Tumor, Primary --- Brain Tumor, Recurrent --- Cancer of the Brain --- Intracranial Neoplasms --- Malignant Neoplasms, Brain --- Malignant Primary Brain Neoplasms --- Neoplasms, Brain --- Neoplasms, Brain, Benign --- Neoplasms, Brain, Malignant --- Neoplasms, Brain, Primary --- Primary Brain Neoplasms --- Primary Malignant Brain Neoplasms --- Primary Malignant Brain Tumors --- Brain Cancer --- Brain Tumors --- Cancer of Brain --- Malignant Primary Brain Tumors --- Neoplasms, Intracranial --- Benign Brain Neoplasm --- Benign Brain Neoplasms --- Benign Neoplasm, Brain --- Brain Benign Neoplasm --- Brain Benign Neoplasms --- Brain Cancers --- Brain Malignant Neoplasm --- Brain Malignant Neoplasms --- Brain Neoplasm --- Brain Neoplasm, Benign --- Brain Neoplasm, Malignant --- Brain Neoplasms, Primary --- Brain Tumor --- Brain Tumors, Primary --- Brain Tumors, Recurrent --- Cancer, Brain --- Cancers, Brain --- Intracranial Neoplasm --- Malignant Brain Neoplasm --- Malignant Brain Neoplasms --- Malignant Neoplasm, Brain --- Neoplasm, Brain --- Neoplasm, Intracranial --- Primary Brain Neoplasm --- Primary Brain Tumor --- Primary Brain Tumors --- Recurrent Brain Tumor --- Recurrent Brain Tumors --- Tumor, Brain --- Tumors, Brain --- Orthopedic Disorders --- Musculoskeletal Disease --- Orthopedic Disorder --- Bone Disease --- Disease, Bone --- Diseases, Bone --- Benign Neoplasms --- Malignancy --- Malignant Neoplasms --- Neoplasia --- Neoplasm --- Neoplasms, Benign --- Cancer --- Benign Neoplasm --- Cancers --- Malignancies --- Malignant Neoplasm --- Neoplasias --- Neoplasm, Benign --- Neoplasm, Malignant --- Neoplasms, Malignant --- Tumor --- Medical Oncology --- Cancer, Embryonal --- Cancer, Embryonal and Mixed --- Embryonal Neoplasms --- Germ Cell Neoplasms --- Germ Cell and Embryonal Neoplasms --- Germ Cell and Embryonic Neoplasms --- Neoplasms, Embryonal --- Neoplasms, Germ Cell --- Neoplasms, Germ Cell and Embryonic --- Germ Cell Cancer --- Germ Cell Tumor --- Neoplasms, Embryonal and Mixed --- Cancer, Germ Cell --- Cancers, Embryonal --- Cancers, Germ Cell --- Embryonal Cancer --- Embryonal Cancers --- Embryonal Neoplasm --- Germ Cell Cancers --- Germ Cell Tumors --- Neoplasm, Embryonal --- Tumor, Germ Cell --- Tumors, Germ Cell --- Neoplasms, Nervous Tissue --- Nerve Tissue Neoplasms --- Nervous Tissue Neoplasms --- Neoplasm, Nerve Tissue --- Neoplasm, Nervous Tissue --- Nerve Tissue Neoplasm --- Nervous Tissue Neoplasm --- Nervous System Disorders --- Neurological Disorders --- Neurologic Disorders --- Disease, Nervous System --- Diseases, Nervous System --- Disorder, Nervous System --- Disorder, Neurologic --- Disorder, Neurological --- Disorders, Nervous System --- Disorders, Neurologic --- Disorders, Neurological --- Nervous System Disease --- Nervous System Disorder --- Neurologic Disorder --- Neurological Disorder --- Neurology --- Cramp-Fasciculation Syndrome --- Fasciculation-Cramp Syndrome, Benign --- Foley-Denny-Brown Syndrome --- Oppenheim's Disease --- Amyotonia Congenita --- Oppenheim Disease --- Benign Fasciculation-Cramp Syndrome --- Benign Fasciculation-Cramp Syndromes --- Cramp Fasciculation Syndrome --- Cramp-Fasciculation Syndromes --- Fasciculation Cramp Syndrome, Benign --- Fasciculation-Cramp Syndromes, Benign --- Foley Denny Brown Syndrome --- Neuromuscular Disease --- Oppenheims Disease --- Syndrome, Cramp-Fasciculation --- Syndrome, Foley-Denny-Brown --- Syndromes, Cramp-Fasciculation --- CNS Diseases --- Central Nervous System Disorders --- CNS Disease --- Histological Type of Neoplasm --- Histological Types of Neoplasms --- Neoplasms by Histological Type --- Neoplasm Histological Type --- Neoplasm Histological Types --- Neoplasms Histological Type --- Neoplasms Histological Types --- Neoplasms by Sites --- Site, Neoplasm --- Sites, Neoplasm --- Neoplasm Site --- Neoplasm Sites --- Cancer of the Bone --- Neoplasms, Bone --- Bone Cancer --- Cancer of Bone --- Bone Neoplasm --- Neoplasm, Bone --- Epithelial Neoplasms --- Glandular Neoplasms --- Glandular and Epithelial Neoplasms --- Neoplasms, Epithelial --- Neoplasms, Glandular --- Neoplasms, Glandular Epithelial --- Epithelial Neoplasm --- Epithelial Neoplasm, Glandular --- Epithelial Neoplasms, Glandular --- Glandular Epithelial Neoplasm --- Glandular Epithelial Neoplasms --- Glandular Neoplasm --- Neoplasm, Epithelial --- Neoplasm, Glandular --- Neoplasm, Glandular Epithelial --- Spinal Cord Disorders --- Myelopathy --- Myelopathies --- Spinal Cord Disease --- Spinal Cord Disorder --- Neuroectodermal Tumor --- Tumor, Neuroectodermal --- Tumors, Neuroectodermal --- Neoplasms, Skull --- Neoplasm, Skull --- Skull Neoplasm --- Brain Disorders --- CNS Disorders, Intracranial --- Central Nervous System Disorders, Intracranial --- Central Nervous System Intracranial Disorders --- Encephalon Diseases --- Encephalopathy --- Intracranial CNS Disorders --- Intracranial Central Nervous System Disorders --- Brain Disease --- Brain Disorder --- CNS Disorder, Intracranial --- Encephalon Disease --- Encephalopathies --- Intracranial CNS Disorder --- Nervous System Tumors --- Tumors of the Nervous System --- Neoplasms, Nervous System --- Neoplasm, Nervous System --- Nervous System Neoplasm --- Nervous System Tumor --- Tumor, Nervous System --- Tumors, Nervous System --- Central Nervous System Neoplasms, Primary --- Central Nervous System Tumors --- Primary Central Nervous System Neoplasms --- Tumors, Central Nervous System --- CNS Neoplasms --- Neoplasms, Central Nervous System --- CNS Neoplasm --- Neoplasm, CNS --- Neoplasms, CNS --- PNS (Peripheral Nervous System) Diseases --- PNS Diseases --- Peripheral Nervous System Disease --- Peripheral Nervous System Disorders --- Peripheral Nerve Diseases --- Peripheral Neuropathies --- Nerve Disease, Peripheral --- Nerve Diseases, Peripheral --- Neuropathy, Peripheral --- PNS Disease --- Peripheral Nerve Disease --- Peripheral Neuropathy --- Brain Metastases --- Brain Metastase --- Central Nervous System Disease --- Central Nervous System Disorder --- Central Nervous System Neoplasm --- Central Nervous System Tumor --- Primary Central Nervous System Neoplasm --- Epithelial Cell Neoplasms --- Glandular Cell Neoplasms --- Cell Neoplasm, Epithelial --- Cell Neoplasm, Glandular --- Cell Neoplasms, Epithelial --- Epithelial Cell Neoplasm --- Glandular Cell Neoplasm --- Neoplasm, Epithelial Cell --- Neoplasm, Glandular Cell