Increased Risk of Testicular Germ Cell Cancer Among Infertile Men

Walsh, Thomas J.; Croughan, Mary S.; Schembri, Michael; Chan, June M.; Turek, Paul J.

doi:10.1001/archinternmed.2008.562

Cited by 229 publications

(164 citation statements)

References 22 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Clinical risk factors for TC include male infertility (RR=3) (Mancini et al, 2007, Walsh et al, 2009) and a history of cryptorchidism (RR=2-8) (Dieckmann andPichlmeier, 2004, Wood andElder, 2009). Some cases of cryptorchidism, male infertility, and most TGCTs share the common feature of foetal developmental origins.…”

Section: Testicular Cancer: Epidemiology and Pathologymentioning

confidence: 99%

Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

Kristensen¹,

Skakkebæk²,

Meyts³

et al. 2013

Int. J. Dev. Biol.

View full text Add to dashboard Cite

Foetal development of germ cells is a unique biological process orchestrated by cellular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study in humans. However, the common precursor of testicular cancers -the carcinoma in situ (CIS) cell -is thought to be an arrested foetal germ cell. Therefore studies of CIS cells may leverage information on human foetal germ cell development and, in particular, when neoplastic transformation is initiated. In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigenetic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic event in the initiation of testicular germ cell cancer. Even though only sparse information is available on epigenetic cues in human foetal germ cells, these indicate that the developmental patterns differ from the findings in mice and emphasize the need for further studies of foetal germ cell development in humans.

show abstract

Section: Testicular Cancer: Epidemiology and Pathologymentioning

confidence: 99%

Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

Kristensen¹,

Skakkebæk²,

Meyts³

et al. 2013

Int. J. Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…However, in accordance to our findings, that study failed to find association between KITLG rs995030 and male infertility. Larger studies are probably needed to correctly assess the possible association between KITLG markers and spermatogenesis, taking into account that, although epidemiological data suggest that male infertility confers a significantly increased risk of TGCT (standardized incidence ratio 2.8, 95% CIZ1.5-4.8; Walsh et al 2009), the prevalence of TGCT in men with infertility or azoooligozoospermia is low (0.3%; Jacobsen et al 2000, Walsh et al 2009). Anyway, the phenotype 'TC' for which association with KITLG variants was found is definite and specific (germ cell tumor, especially the seminoma subtype), whereas male infertility is clearly a multifactor entity.…”

Section: Discussionmentioning

confidence: 99%

Variants in KITLG predispose to testicular germ cell cancer independently from spermatogenic function

Ferlin¹,

Pengo²,

Pizzol³

et al. 2011

Endocrine-Related Cancer

View full text Add to dashboard Cite

Epidemiological data suggest an association and a common pathogenetic link between male infertility and testicular germ cell tumor (TGCT) development. Genome-wide studies identified that TGCT susceptibility is associated with KITLG (c-KIT ligand), which regulates the formation of primordial germ cells, from which TGCT is believed to arise and spermatogenesis develops. In this study, we analyzed the link between KITLG, TGCT, and spermatogenic disruption by performing an association study between the KITLG markers rs995030 and rs4471514 and 426 TGCT cases and 614 controls with normal and abnormal sperm count. We found that TGCT risk was increased more than twofold per copy of the major G allele and A allele in KITLG rs995030 and rs4471514 (odds ratio (OR)Z2.38, 95% confidence interval (95% CI)Z1.81-3.12; ORZ2.43, 95% CIZ 1.86-3.17 respectively), and homozygotes for the risk allele had a sevenfold increased risk of TGCT. KITLG markers were strongly associated with seminoma subtype (per allele risk increased more than threefold, homozygote risk increased by 13-to 16-fold) and weakly with nonseminoma. KITLG markers were not associated with sperm production, as no difference was observed in men with normozoospermia and azoo-oligozoospermia, both in controls and in TGCT cases. In conclusion, this study provides evidence that KITLG variants are involved in TGCT development and they represent an independent and strong specific risk factor for TGCT independently from spermatogenic function. A shared genetic cause and a common pathogenetic link between TGCT development and impairment of spermatogenesis are not evident from this study.

show abstract

“…Bij patiënten met een testistumor is azoö-spermie of cryptozoöspermie zonder motiele zaadcellen de belangrijkste risicofactor. De gedeelde pathofysiologie van afwijkende spermatogenese, infertiliteit, cryptorchisme en testistumorontwikkeling, zoals beschreven in het testiculaire dysgenesiesyndroom is hiervoor een mogelijke verklaring [17,18].…”

Section: Discussieunclassified

20 jaar semencryopreservatie: haalbaarheid en verwijspatronen

et al. 2018

View full text Add to dashboard Cite

SamenvattingBehandeling van kanker kan de spermatogenese aantasten, met infertiliteit tot gevolg. Semencryopreservatie voorafgaand aan gonadotoxische behandeling kan de vruchtbaarheid van mannelijke kankerpatiënten veiligstellen. Gedurende 20 jaar zijn 1.018 patiënten tussen 12 en 50 jaar oud, met Hodgkin-lymfoom (n = 194), non-Hodgkin lymfoom (n = 110), leukemie (n = 126) of testiculaire kiemceltumoren (n = 588) verwezen naar één centrum voor semencryopreservatie. De incidentie van deze kankertypen in het adherentiegebied en de incidentie van regionale semencryopreservatie werd gebruikt om een verwijsratio te berekenen. Semencryopreservatie was succesvol bij 856 van de 1.018 patiënten (84,1 %). De mediane jaarlijkse verwijsratio bij hematologische maligniteiten en testiculaire stamceltumoren was respectievelijk 17 % en 31 %. De regionale verwijzing bij hematologische maligniteiten daalde na 2005 fors, tot een minimum van 2 % in 2009, terwijl deze toenam bij testiculaire kiemceltumoren. Onze resultaten tonen aan dat verwijzing voor semencryopreservatie bij patiënten met een hematologische maligniteit in de fertiele leeftijd suboptimaal is.Trefwoorden semencryopreservatie · verwijzing · fertiliteit · hematologische maligniteiten · testiculaire kiemceltumoren 20 years of semen cryopreservation: feasibility and referral behavior Abstract Treatment of cancer can affect spermatogenesis resulting in infertility. Semen cryopreservation prior to gonadotoxic treatment can be offered to secure future fertility in male cancer patients. During 20 years 1,018 patients referred for semen cryopreservation in fertile age with Hodgkin disease (n = 194), non-Hodgkin lymphoma (n = 110), leukemia (n = 126) and testicular germ cell tumor (n = 588) were followed up. Incidence of these cancers and incidence of regional semen cryopreservation was used to calculate a referral rate. Semen cryopreservation was successful in 856 of 1,018 patients (84.1%). Median yearly referral rate was respectively 17% and 31% in hematological malignancies and testicular germ cell tumor. Regional referral rate in hematological malignancies dropped dramatically after 2005 to a minimum of 2% in 2009. The incidence of TGCT and referral rate for fertility preservation in these patients increased over time. Our result show that referral of for semen cryopreservation in patients with hematological malignancies in fertile age is suboptimal. IntroductieDe overleving van patiënten met een maligniteit is de afgelopen decennia sterk verbeterd, met name door combinatiechemotherapie-schema's. De verbeterde overleving gaat gepaard met toenemende aandacht voor langetermijneffecten van oncologische behandelingen, waaronder gonadotoxische schade, die kan leiden tot (ir)reversibele infertiliteit. Oncologische patiënten rapporteren verlies van kwaliteit van leven wanneer zij ten gevolge van de therapie geen kinderen kunnen verwekken [1,2]. Daarnaast kan subferti-

show abstract

Increased Risk of Testicular Germ Cell Cancer Among Infertile Men

Cited by 229 publications

References 22 publications

Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

Variants in KITLG predispose to testicular germ cell cancer independently from spermatogenic function

20 jaar semencryopreservatie: haalbaarheid en verwijspatronen

Contact Info

Product

Resources

About