Male Infertility Male Infertility and Testicular Cancer – Points of Common Causality Ashok Agarwal,1 Whitney R Burns,2 Rima Dada3 and Edmund S Sabanegh, Jr4
1. Director, Center for Reproductive Medicine, Glickman Urological and Kidney Institute, Cleveland Clinic; 2. Medical Student, University of Virginia; 3. Associate Professor, All India Institute of Medical Sciences; 4. Chairman, Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic
Abstract
Testicular cancer and male infertility are male reproductive health problems that have increased in frequency in the past few decades. Our article examines the relationship between these two disease states, focusing particularly on those causal mechanisms that link the two. Genetic mechanisms, including mutations in the SRY and p53 genes, as well as persistent oxidative stress, have been associated with both of these diseases. Endocrine-disrupting chemicals have also been implicated in the aetiology of both infertility and testicular cancer. The shared aetiology of these two disease states is strongly indicative of a link between male infertility and testicular cancer. While future research will undoubtedly strengthen the relationship between them, the current knowledge on this subject makes a persuasive case for careful consideration of this link when clinicians are making treatment decisions for patients with infertility or testicular cancer.
Keywords Male infertility, testicular cancer, endocrine disruption, testicular dysgenesis, SRY gene mutation, p53 gene mutation, oxidative stress
Disclosure: The authors have no conflicts of interest to declare. Acknowledgement: Research support for this study was provided by the Center for Reproductive Medicine, Cleveland Clinic. Received: 17 March 2010 Accepted: 29 June 2010 Citation: European Urological Review, 2010;5(1):56–9 Correspondence: Ashok Agarwal, Professor and Director, Center for Reproductive Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk A19.1, Cleveland, OH 44195, US. E:
agarwaa@ccf.org
In recent years, male reproductive health has declined markedly in developed countries. Semen quality has decreased and, consequently, the number of infertile males has increased. Additionally, there has been a six-fold increase in the incidence of testicular cancer. Recent studies have found the infertile population to be at increased risk of developing gonadal tumours, suggesting that there is a possible association between these two health problems.
This article explores the link between male infertility and testicular cancer by presenting information on the genetic and environmental basis of this linkage. The evidence presented in this article strongly suggests that there is a causal relationship between male infertility and testicular cancer. It is our hope that clinicians will be able to use this evidence to guide their treatment decisions when caring for patients diagnosed with infertility or testicular cancer.
Current Risk Factors for Testicular Cancer Although many potential risk factors for germ cell tumours have been proposed, few of the claims have been substantiated. Thus far, only cryptorchidism, contralateral testicular germ cell tumour and familial history of testicular cancer have proved to be sound predictors of testicular cancer risk. A meta-analysis of 20 case–control studies conducted by Dieckmann found the relative risk of testicular germ cell tumours in individuals with a history of undescended testes to be five times greater than that of men without such a history. Men with a familial history of testicular cancer are three to 10 times more likely to develop it themselves, perhaps by inheriting a susceptibility gene on the X chromosome.
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Additionally, patients with unilateral testicular germ cell tumours possess a much greater risk of developing a contralateral germ cell tumour.1
Incidence and Known Causes of Male Infertility Infertility affects roughly 15% of couples.2
Most cases are considered
idiopathic. Both non-genetic and genetic factors contribute by influencing physiological processes related to spermatogenesis. Genetic abnormalities are associated with approximately 15–30% of male infertility cases.3
Structural defects are responsible for a small proportion of all male infertility cases.
Association of Male Infertility and Testicular Cancer
Some studies have looked retrospectively at the pre-cancer fertility capacity of men who later developed testicular cancer. For example, it has been shown that men who develop testicular cancer have fewer children than age-matched men who do not develop testicular cancer.4
A study by Petersen and Skakkebaek analysed the semen quality of men diagnosed with unilateral testicular cancer. This group reported that the quality of semen collected from these men was much poorer than would typically be expected for a man possessing one functional testicle.5
Carcinoma in situ (CIS), a
pre-cancerous cellular condition, is also seen more frequently in the testicular biopsies of men evaluated for sub-fertility or infertility.6 This would strongly suggest that men with fertility problems, even those who go undiagnosed with sub-fertility, are at an increased risk of developing testicular cancer.
© TOUCH BRIEFINGS 2010
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