Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype

Abstract

Familial aggregations of testicular germ cell tumor (FTGCT) have been well described, suggesting the existence of a hereditary TGCT subset. Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to sixfold and eight- to tenfold increases in TGCT risk respectively. Segregation analyses suggest an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest, although no high-penetrance cancer susceptibility gene has been mapped yet. These data suggest that the combined effects of multiple common alleles, each conferring modest risk, might underlie familial testicular cancer. Families display a mild phenotype: the most common number of affected families is 2. Age at diagnosis is 2–3 years younger for familial versus sporadic cases. The ratio of familial seminoma to nonseminoma is 1.0. FTGCT is more likely to be bilateral than sporadic TGCT. This syndrome is cancer site specific. Testicular microlithiasis is a newly recognized FTGCT component. Candidate gene-association studies have implicated the Y chromosome gr/gr deletion and PDE11A gene mutations as genetic modifiers of FTGCT risk. Two genomewide association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers. All five loci are involved in normal testicular development and/or male infertility. These genetic data provide a novel insight into the genetic basis of FTGCT, and an invaluable guide to future TGCT research.

Testicular cancer in two brothers of a quadruplet: a case report and a review of literature

“…Sons have four-to six-fold, while siblings of testicular GCT patients have eight-to ten-fold increase in testicular GCT risk, respectively. Segregation analyses suggest an autosomal recessive mode of inheritance (14).…”

Epidemiological trends of hormone-related cancers in Slovenia

“…Some risk factors also involve exposure to hormones in utero (cryptorchidism, hypospadias, inguinal hernia, low birth weight, short gestational age, and being a twin) or to endogenous hormones (45). Established risk factors for testicular germ cell tumours also include a prior testicular germ cell tumour, a family history of germ cell tumour and various inter-sex syndromes (46,47). There are very interesting migrant studies that suggest environmental and dietary factors.…”

“…Men with a first-degree relative with testicular cancer run a three to ten times higher risk of being diagnosed with the disease (46).…”

Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X

“…The disease models underpinning multiple familial cancers such as familial nasopharyngeal carcinoma, 112 familial testicular germ cell tumor, 113 familial chronic lymphocytic leukemia, 114 and familial colorectal cancer (familial colorectal cancer type X) 29 remain contentious as the high-penetrance mutations are yet to be identified. By contrast, multiple low-penetrance variants that confer an effect size of odds ratio o1.5 have been revealed through genome-wide association studies for the sporadic cases of these cancers; interestingly, some of these single-nucleotide polymorphisms have also been found to be associated with the familial cases (nasopharyngeal carcinoma, 115 testicular germ cell tumor, 116,117 chronic lymphocytic leukemia, 118,119 and colorectal cancer 120 ).…”