The main hypothesis explained you question is that testicular germ cell tumours are derived from foetal gonocytes, that did not undergo correct differentiation into spermatogonia within testes. Pubertal gonadotripins levels stimulate germ cell proliferation (normal - spermatogonia, and abnormal). Spermatogonia proliferate and differentiate into spermatozoa. Abnormal cells (foetal not differentiated gonocytes) have neoplastic potential and proliferate into overt tumour.

I am not a seasoned researcher but just a fresh medical graduate, however since this is my research topic, I would like to add to the discussion.

Skakkebak et al proposed that according to the concept of testicular dysgenesis syndrome (TDS), various male reproductive disorders such as hypospadias, undescended testis, testicular germ cell cancer and low sperm counts may be linked to a common origin in early fetal life; caused by the abnormality in testicular development resulting in Sertoli and/or Leydig cell dysfunction.

As we know cryptorchidism, hypospadias is seen in newborns, while reduce fertility is commonly seen in young adults. Testicular cancer can thus be proposed to be a part of this spectrum hence like other disorders of TDS it presents at early age, as the insult is hypothesized to take place in utero.

Hsieh et al & Eisenberg et al has reported anogenital distance (AGD), a marker of androgenisation set during gestation to be shorter in people with cryptorchidism, hypospadias and infertile young men. It may be possible this AGD is also shorter in men with testicular cancer (which is part of my research topic )

I am not an PHD, or MD, so all I can add is you take a look at the continous intake of artificial estrogens, like Bisphenol-A, and Bisphenol-S, and many other Bisphenols, through waterbottles, etc. I will cite just two studies:

(http://dx.doi.org/10.1016/j.mce.2006.04.033)

(http://dx.doi.org/10.1016/S0045-6535(99)00380-X)

Take also a look at Phtalates, and other newly dangerous chemicals in our everyday environment. I wont cite any more studies because they are so numerous, you should just browse the scientific literature. Well, I'll leave you with just this one:

(http://dx.doi.org/10.1530/rep.1.00025)

Also, do not exlcude the way adolescents (from 15 year's age) and adults (till 50 year's old) carry their mobile phones, or POCKET-phones - in their pocket, right next to their testicles. I will cite just one study:

(http://dx.doi.org/10.1111/j.1365-2605.2006.00721.x)

Moblie phones are maybe 30 years old, and since mostly adolescents and adults use them, it would correspond with the risk age you asked about.

And, why not, the LAP-top computer, having it deposited many times on top of your lap, and your, yes again, testicles.

I will finish off, my non-high quality answer, with a hint: it might be a combination of all these possible factors: an early-age exposition to Bisphenols, and a child-age exposure to Bisphenols and Phtalates and others, and an adolescent-age exposure to Mobile phones, laptop computers, Bisphenols and Phtalates, etc., and this continuing into adulthood.

I wish you the best of luck with finding the right, or best right answer. I hope you take my suggestions into consideration.

The only snippet added on to Oszukowska is that delayed disappearance of gonocytes and appearance of adult dark (Ad) spermatogonia reflects failure of postnatal activation of the HPG axis, which is seen in cryptorchidism and that may be the reason for higher risk of GCT in cryptorchids

I agree with previous comments, the origin is suppose to be during fetal life. The germ cells PGCs must be exposed during this period of life. However as for other cancers it must be multifactorial. Thus there might be a second it and increase levels or alteration by endocrine disrupters off hormone at puberty may contribute to the development of testicular cancer.

We have a long way to go before understanding Testis cancer ethiology.

Hi everybody. Thanks for your participation. I read about the effect of pubertal gonadotropins in some papers but the common view is that it still remains an hypothesis and I agree we don't actually fully understand the testicular cancer biology. On the other side I don't think mobile phones play a role in this, the age risk of testicular cancer has always been mostly 15-45. It could play a role on the highest incidence reported in the last three decades. However I think that to have some information about the effect of mobile phone on human health we would need large studies and on a long time term. The heat produced by laptop or particular underwear can induce a sort of damage in the testicular function (spermatogenesis) but to the best of my knowledge there is no suggested association with a possibility to develop testicular cancer.

The story of the mobile phones seems irrelevant. The cancers indeed result from testicular dysgenesis, very probably related to exposure of the mother to hormone disrupting agents, xeno-estrogen estrogens and aniti-androgens. The tumors take several years to develop, as almost all cancers do, which explain the time-window. The causal link between hormone disruption and testicular cancer derives from animal experiences, and the use of diethylstilboestrol in pregnant women in the fifties.

Hello every body. I have studied the effects of Electro-Magnetic field (2.5GHz) produced by Lap Top computer in the rat model. We compare the short term (1houre) and the long term (7houres) effects of this kind of EMF. Both of them increased the apoptosis of germ cells after 8 weeks exposure. Actually, We could not seen any thing that shows Testis cancer.

Thank you, Saeed, for sustaining my statement that electro-magnetic field is irrelevant to testicular cancer. It might, perhpas, be of influence regarding certain brain tumors, in cirtain cicumstances, and particularly in young children. We found the load of surface waters in particular regions in Flanders regarding xeno-estrogens to be extremely high. These substances will enter the human body, fat tissue in particular, through the food chain. Women who are pregnant will introduce and transfer these substances to their fetus, causing severe damage to the gonads, and to the development of reproductive organs.

Thank you all for putting in your opinions, studies and experiences. This is a very important subject, cause, even though it is originaly intended for testicular cancer, it also touches reproductive problems, which are undoubtly rising enormously, almost worldwide, though more in the developed nations. One in five men are having problems with infertility, as sperm quality and cuantity decline rapidly. Testicular cancer is on the rise, well, almost all cancers are on the rise, and not exactly at a slow rate.

I understand that laptop computers and mobile phones might not be direct causes for testicular cancer, but still I would like to point out: might a combination between artificial hormones mimicking estrogen, like Bisphenol-A, and the recent replacements, Bisphenol-S, from the day one is a fetus to adulthood, and Phtalates, and mobile phones and laptop computers, all combined, be a posible combination-trigger, causing reproductive cancers. I might offcourse be dead wrong.

Lets nor forget that ovarian cancer is also on the rise, as is breast cancer, and both might also be caused, in part, by artificial estrogens, cause girls also take these in, since prebirth. I think that if you really wanna get further investigating testicular cancer, you should try putting conexiones between other reproductive cancers, and the posible relations they might have with elements in our environment, food and watersupply, whatever these might be.

I wish you all the best of luck. It is an urgent and serious subject.

Various Endocrine Disruptors may be a a pausible cause as shown by many studies, which also supports the TDS hypothesis. Its a combination of various lifestyle, environmental factors in a genetically susceptible individual. Studies have shown higher incidence of testicular cancer among certain ethnicity in cohort of people residing in same geography and occupation. Its difficult to pinpoint a single cause.

Impact of puberty and its hormonal stimulation of immature pretumoral quiescent cells (NGIT as discribed by skakkebaeck) might be interesting to consider as an explanation of the early (peripubertal and young adults) onset of germ cell tumors. The dysgenetic syndrome (DGS) hypothesis is also interesting but will not explain why germ cell tumors of mediastinum and central nervous system (that are not related to DGS) also occur in young adults. Unless a genetic common factor related to these DGS (cryptorchidism hypofertlilty testicular germ cell tumors) is also involved in GCT at any location ? Does anyone knows ?

As far as I know there are no genetic common factors. Thanks everybody for your contribution. I would love to extend testicular cancer research after my PhD.I will start to look around the next year I would like to move to USA for my post-doc. regards

Likely Causes of age-dependent Testicular Cancer/Tumours

1. FSH synthesis is up-regulated by Activin secreted by the Sertoli cells.

2. FSH activity is regulated by prostatic(?) follitropin which binds to it.

3. FSH release is inhibited by Inhibin secreted by Sertoli cell.

4. Over-expression of Activin is known to lead to testicular tumours, especially if there is a concerted deficit of Inhibin.

5. Inhibin is a marker of tumour in testis.

6. Steroids are intimately involved in the feedback loops of FSH regulation.

7. Low estradiol status is a cause of peripheral FSH increase which suggests a dysregulation in feedback regulation at both pituitary as well as testicular levels.

8. Hyperandrogenism could be a cause of low estradiol due to inhibition of P450 aromatase in the testis.

9. Hyperandrogenism couldbe inherited/congenital and arise because of genetic defects in steroidogenic enzymes.

10. Low estradiol would affect/reduce negative feedback regulation of T synthesis in Leydig cells.

11. Low estradiol could affect the feedback regulation at the level of GnRH in the hypophysis.

12. Low estradiol could reducerate of pruning/apoptosis of meiotic/mitotic cells around Sertoli cells regulated through beta estrogen receptor.

13. Higher FSH levels could shift the delicate homeostasis around the Sertoli cell and shift the balance towards mitosis which is also under the regulation of estradiol through alpha estrogen receptor.

14. If alpha ER has specific polymorphisms in some males, they would be genetically more susceptible to excessive mitotic activity and tumours.

15. Cancer, unlike tumours which are hormonal, could have a microbial/retroviral origin, to which a fetus may have been exposed in utero/post-natal. This would lead to irreversible transformation of enzyme/s in vivo and cancer.

16. All these conditions would be present/manifest only in the sexually active/reproductive phase of the males when the reproductive system is in full action.

Hope this helps when you move for your PhD.

Thanks nice summary. I am actually working with activin and inhibin now :)

In my view the TDS story's the most compelling as it explains a variety of perturbations in male reproductive health due to developmental exposure to chemicals (possibly anti-androgens and others). Indeed, carcinoma in situ has been shown to have a foetal origin, and men born with hypospadias and cryptorchidism are at higher risk of testicular cancer in adulthood. Not a good prospect for males really!

We are just taking in the young age

there is a age range starting with around 50 years - with a higher incidence of testicular cancer

low estradiol could play an important role?

Yes it is true but the fascinating thing of testicular cancer is the highest incidence in young men. The gonadotropin play an essential role in the evolution of testicular cancer , but the fact itself that something with foetal origin as Edwin said then develop in cancer (during a time when there is a maximal activity of male hormones) is very important to consider. I originally posted this question to see if some "alternative hypothesis" were stated by someone.

I have read with interest all your comments. I want to draw your attention and ask you at the same time if you hadn't faced in your clinical practice an increased risk in young patients smoking regularly Marijuana? 

I am not aware of any study correlating Marijuana with an increase incidence of developing testicular cancer.

No there are no studies but interestingly 3/4 of our patients confess being regular smokers

That could be because of the young age, and because smoking is marijuana is more common in young people.......maybe?