A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer—experiences of the son

Cook, Michael B.; Akre, Olof; Forman, David; Madigan, M. Patricia; Richiardi, Lorenzo; McGlynn, Katherine A.

doi:10.1093/ije/dyq120

Cited by 140 publications

(125 citation statements)

References 91 publications

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“…Despite the strong evidence for heritability, the only TGCT susceptibility factors identified in genome-wide association studies are the gr/gr deletion on the Y chromosome and autosomal variants in KITLG, SPRY4, BAK1, and DMRT1, which together account for less than 10% of risk (10)(11)(12)(13)(14). The substantial difference in prevalence between sons and brothers of cases and the epidemiological evidence for maternal estrogens, birth order, birth weight, and other factors (15)(16)(17) together raise the possibility that maternal conditions, epigenetic effects, and perhaps unconventional modes of inheritance also contribute to TGCT risk (18).…”

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confidence: 99%

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Nelson

Heaney

Tesar

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Environmental agents and genetic variants can induce heritable epigenetic changes that affect phenotypic variation and disease risk in many species. These transgenerational effects challenge conventional understanding about the modes and mechanisms of inheritance, but their molecular basis is poorly understood. The Deadend1 (Dnd1) gene enhances susceptibility to testicular germ cell tumors (TGCTs) in mice, in part by interacting epigenetically with other TGCT modifier genes in previous generations. Sequence homology to A1cf, the RNA-binding subunit of the ApoB editing complex, raises the possibility that the function of Dnd1 is related to Apobec1 activity as a cytidine deaminase. We conducted a series of experiments with a genetically engineered deficiency of Apobec1 on the TGCT-susceptible 129/Sv inbred background to determine whether dosage of Apobec1 modifies susceptibility, either alone or in combination with Dnd1, and either in a conventional or a transgenerational manner. In the paternal germ-lineage, Apobec1 deficiency significantly increased susceptibility among heterozygous but not wild-type male offspring, without subsequent transgenerational effects, showing that increased TGCT risk resulting from partial loss of Apobec1 function is inherited in a conventional manner. By contrast, partial deficiency in the maternal germ-lineage led to suppression of TGCTs in both partially and fully deficient males and significantly reduced TGCT risk in a transgenerational manner among wild-type offspring. These heritable epigenetic changes persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germ-lineage. These results suggest that Apobec1 plays a central role in controlling TGCT susceptibility in both a conventional and a transgenerational manner.epigenetics | testicular cancer | gametogenesis | epistasis E stablishing the genetic basis and mode of inheritance for most traits and diseases has proven to be remarkably elusive (1). Susceptibility to testicular germ cell tumors (TGCTs) is illustrative (2). Testicular cancer is the most common malignancy affecting young men (3), more than 90% of testicular cancers result from TGCTs (4), TGCTs rank third in heritability among all cancers (5), and family history is the strongest known risk factor with a two-to sixfold increase among sons and a 5-to 19-fold increase among brothers of affected individuals (6-9). Despite the strong evidence for heritability, the only TGCT susceptibility factors identified in genome-wide association studies are the gr/gr deletion on the Y chromosome and autosomal variants in KITLG, SPRY4, BAK1, and DMRT1, which together account for less than 10% of risk (10-14). The substantial difference in prevalence between sons and brothers of cases and the epidemiological evidence for maternal estrogens, birth order, birth weight, and other factors (15-17) together raise the possibility that maternal conditions, epigenetic effects, and perhaps unconventional modes of inheritance also contribute to TG...

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confidence: 99%

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Nelson

Heaney

Tesar

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Cryptorchidism is a significant risk factor for testicular cancer (14,15). In the present case, the patient had possessed a history of cryptorchidism for the previous 30 years.…”

Section: Discussionmentioning

confidence: 65%

Adult metastatic yolk sac tumor descending from an intra-abdominal testis: A case report and review of the literature

et al. 2015

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Abstract. Pure yolk sac tumors are extremely rare in adults; to the best of our knowledge, <20 cases have been reported. Multiple metastases originating from a pure yolk sac testicular tumor, descending from an intra-abdominal testis, are additionally extremely rare. In the present case, a man exhibiting a 30-year history of cryptorchidism and indirect inguinal hernia, was admitted to the Department of Urology (The Second Xiangya Hospital, Changsha, China) due to a mass that had descended from the abdominal cavity 7 months previously. Elevated levels of specific serum marker (α-fetoprotein, lactate dehydrogenase and human chorionic gonadotropin ) did not indicate potential testicular germ cell types prior to surgery and pathological examination. Pathological results and immunohistochemistry revealed a testicular pure yolk sac tumor subsequent to surgery. The present case report and literature review describes the typical characteristics of an adult testicular yolk sac tumor, as well as the diagnosis and management of the disease.

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“…However, the lack of confounding effect by birth weight is not unexpected as low birth weight is associated with only a weak increase in risk of testicular cancer. 4 In our study, we also considered age at puberty in the analyses. Age at puberty has been previously associated with Including mixed germ-cell cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Cryptorchidism, family history, history of testicular cancer and ethnicity are established risk factors, 2 and prenatal exposures are likely to play a role. 3,4 Adult height has been repeatedly associated with an increased risk of testicular cancer. A recent meta-analysis estimated a 13% increase in risk with each 5-cm increase in adult height.…”

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confidence: 99%

Lifetime growth and risk of testicular cancer

et al. 2014

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Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in [1997][1998][1999][2000][2001][2002][2003][2004][2005][2006][2007][2008] and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (<167 cm or less), the OR of testicular cancer for tall (>180 cm) vs. short (<174 cm) subjects was 3.47 (95% CI: 1.60-7.51). These results suggest that the association between height and testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence.Testicular cancer is the most frequent male tumour among young adults and has been increasing in incidence over the last few decades in many populations.1 Its aetiology is still largely unknown. Cryptorchidism, family history, history of testicular cancer and ethnicity are established risk factors, 2 and prenatal exposures are likely to play a role. 3,4 Adult height has been repeatedly associated with an increased risk of testicular cancer. A recent meta-analysis estimated a 13% increase in risk with each 5-cm increase in adult height.5 Indeed, height is at present the strongest potential risk factor for testicular cancer, in terms of the population attributable risk. However, height is considered to be affected by both environmental and genetic factors, and the possible explanations for the association between height and testicular cancer have not been fully investigated.6,7 Adult height could be a proxy for genetic variants associated with the risk of testicular cancer or it could be a proxy for environmental exposures causing testicular cancer. Furthermore, these environmental exposures could act at different stages of life from the prenatal life to childhood and adolescence and it would be important to identify whether there are specific periods (for example, prenatal life or childhood) in which height-related environmental exposures could affect the risk of testicular cancer.In the a...

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A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer—experiences of the son

Abstract: In conclusion, this systematic review and meta-analysis finds evidence that cryptorchidism, inguinal hernia and twinning, and tentative evidence that birth weight and gestational age, are associated with risk of testicular cancer.

Cited by 140 publications

References 91 publications

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Adult metastatic yolk sac tumor descending from an intra-abdominal testis: A case report and review of the literature

Lifetime growth and risk of testicular cancer

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