Cancer Risk in Men Exposed In Utero to Diethylstilbestrol

Strohsnitter, William C.; Noller, Kenneth L.; Hoover, Robert N.; Robboy, Stanley J.; Palmer, Julie R.; Titus-Ernstoff, Linda; Kaufman, Raymond H.; Adam, Ervín; Herbst, Arthur L.; Hatch, Elizabeth E.

doi:10.1093/jnci/93.7.545

Cited by 179 publications

(96 citation statements)

References 36 publications

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“…It was shown that DES exposure in the third generation still leads to an increased risk of hypospadias (Brouwers et al, 2006). The risk of GCC development in this patient group is controversial, and a slightly increased risk has been reported (Strohsnitter et al, 2001).The transgenerational effect of DES is however suggestive for heritable epigenetic alterations. In addition, exogenous estrogen may interrupt the maturation of primitive germ cells by reducing the secretion of Anti-Mϋllerian hormone from the Sertoli cells (Longnecker et al, 2002).…”

Section: Environmental Factors In the Pathogenesis Of Gccmentioning

confidence: 99%

Role of epigenetics in the etiology of germ cell cancer

Zwan¹,

Stoop²,

Rossello³

et al. 2013

Int. J. Dev. Biol.

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Embryonic development is strictly controlled by functionality of genes in which the existing networks can act both on transcription and translation regulation. Germ cell cancers (GCC) are unique because of a number of characteristics. In spite of their clinical presentation, i.e., predominantly after puberty, they arise from primordial germ cells/gonocytes that have failed appropriate maturation to either pre-spermatogonia or oogonia. GCC mimic embryonal development to a certain extent, including capacity for totipotency. This knowledge has allowed the identification of informative diagnostic markers, including OCT3/4 (POU5F1), SOX2 and SOX17. An additional marker is the overall demethylated status of the genome. Genetic mutations in GCC are rare, which is exceptional for solid cancers. Our hypothesis is that a disturbed epigenetic regulation (through combined interaction of genetic or environmental parameters; referred to as genvironment) affect embryonic germ cell development, resulting in delayed or blocked maturation, and potentially progression to GCC. In this respect, studies of patients with Disorders of Sex Development (DSD) have increased our knowledge significantly. Genvironmental influences can lead to retention of existence of embryonic germ cells, the first step in the pathogenesis of GCC, resulting into the precursor lesions gonadoblastoma or carcinoma in situ. Identification of epigenetic alterations could lead to better understanding these processes and development of specific markers for early detection, eventually leading to development of targeted treatment. This review describes an interactive model related to the role of epigenetics in GCC pathogenesis, focusing on DNA methylation, histone modifications, epigenetic memory and inheritance, as well as environmental factors.

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Section: Environmental Factors In the Pathogenesis Of Gccmentioning

confidence: 99%

Role of epigenetics in the etiology of germ cell cancer

Zwan¹,

Stoop²,

Rossello³

et al. 2013

Int. J. Dev. Biol.

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show abstract

“…Additionally, acute lymphoblastic leukemia and Hodgkin's disease are suggested to be related to an infectious etiology, the former by unknown microbial agents and the latter by EBV (6,17,18). Another consistency is that testicular tumors (embryonal tumors are usually mixed with other histologic types) seem to be associated with prenatal estrogenic exposure, and appendiceal carcinoids are neuroendocrine tumors producing serotonin and bioactive peptides (19)(20)(21). Appendiceal carcinoids are usually asymptomatic, more frequent in females than in males, and often diagnosed at appendectomies (20).…”

mentioning

confidence: 99%

Risk of Cancer among the Offspring of Women Who Experienced Parental Death during Pregnancy

Bermejo

Sundquist

Hemminki

2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Cases were diagnosed up to 34 years of age (later extended to 48 years of age), at which time more than 700 cases had been recorded by the registry (Herbst, 1999). In contrast, men who were exposed to DES in utero do not have a clearly increased risk of any cancer, although a statistically non-significant threefold increased risk of testicular cancer has been reported (Strohsnitter et al, 2001). …”

Section: Female Reproductive Tractmentioning

confidence: 99%

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Liu

Xia

Guo

et al. 2012

J Expo Sci Environ Epidemiol

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The urinary metabolites of phthalates are well-accepted exposure biomarkers for adults and children older than 6 years but are not commonly used for infants owing to non-convenient sampling. In the light of this situation, a novel sampling method based on monitoring the urine expressed from the gel diaper was developed. The urine was expressed from the gel absorbent after mixing the absorbent with CaCl2 and then collected by a laboratory-made device; the urinary phthalate metabolites were extracted and cleaned using a solid-phase extraction (SPE) column and analyzed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate the method's feasibility, the following factors were investigated: the proportion of CaCl2 to gel absorbent, the urination volume variation and the target compounds' deposition bias in the diaper, the matrix blank of the different diaper brands, the storage stabilities and the recoveries of creatinine and phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the urine can be expressed from the diaper, and the expressed spiking recoveries and the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50 ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper samples from 15 infants, and the pilot data suggests the infants are commonly exposed to phthalates. In summary, the method for monitoring of infant exposure to phthalates is sound and validated, and the potential health effects from the vulnerable infants' exposure to phthalates should be concerned.39th Scientific Research Foundation for the Returned Overseas Chinese Scholars (SRF for ROCS); Hundred Talent Program of Chinese Academy of Sciences (CAS); CAS/SAFEA International Partnership Program for Creative Research Teams [KZCX2-YW-T08

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Cancer Risk in Men Exposed In Utero to Diethylstilbestrol

Abstract: To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer.

Cited by 179 publications

References 36 publications

Role of epigenetics in the etiology of germ cell cancer

Role of epigenetics in the etiology of germ cell cancer

Risk of Cancer among the Offspring of Women Who Experienced Parental Death during Pregnancy

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

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