Abstract
Background/objectivesIt has been suggested that subfertility and testicular cancer share genetic and environmental risk factors. We studied both subfertility and the strongest known testicular cancer susceptibility gene, the c-KIT ligand (KITLG), whose pathway is involved in spermatogenesis.MethodsThe EPSAM case-control study is comprised of testicular cancer patients from the Province of Turin, Italy, diagnosed between 1997 and 2008. The present analysis included 245 cases and 436 controls from EPSAM, who were aged 20 years or older at diagnosis/recruitment. The EPSAM questionnaire collected information on factors such as number of children, age at first attempt to conceive, duration of attempt to conceive, use of assisted reproduction techniques, physician-assigned diagnosis of infertility, number of siblings, and self-reported cryptorchidism. Genotyping of the KITLG single nucleotide polymorphism (SNP) rs995030 was performed on the saliva samples of 202 cases and 329 controls.ResultsTesticular cancer was associated with the number of children fathered 5 years before diagnosis (odds ratio (OR) per additional child: 0.78, 95% confidence interval (CI): 0.58–1.04) and sibship size (OR per additional sibling: 0.76, 95% CI: 0.66–0.88). When considering the reproductive history until 1 year before diagnosis, attempting to conceive for at least 12 months or fathering a child using assisted reproduction techniques was not associated with the risk of testicular cancer, nor was age at first attempt to conceive or physician-assigned diagnosis of infertility. The SNP rs995030 was strongly associated with risk of testicular cancer (per allele OR: 1.83; 95%CI: 1.26–2.64), but it did not modify the association between number of children and the risk of testicular cancer.ConclusionThis study supports the repeatedly reported inverse association between number of children and risk of testicular cancer, but it does not find evidence of an association for other indicators of subfertility.
Highlights
Testicular cancer is a relatively rare malignancy and occurs most commonly in young and middle-aged men [1, 2]
Testicular cancer was associated with the number of children fathered 5 years before diagnosis (odds ratio (OR) per additional child: 0.78, 95% confidence interval (CI): 0.58–1.04) and sibship size (OR per additional sibling: 0.76, 95% CI: 0.66–0.88)
When considering the reproductive history until 1 year before diagnosis, attempting to conceive for at least 12 months or fathering a child using assisted reproduction techniques was not associated with the risk of testicular cancer, nor was age at first attempt to conceive or physician-assigned diagnosis of infertility
Summary
Testicular cancer is a relatively rare malignancy and occurs most commonly in young and middle-aged men [1, 2]. The incidence of testicular cancer is low worldwide, over the last decades it has increased by 3–4% per year in several populations [3]. There is a large amount of literature on the association between subfertility and the risk of testicular cancer. Large register-based studies in the Nordic countries found that men with testicular cancer fathered fewer children before their diagnosis than did their corresponding control populations [5,6,7], and this association has been replicated in other case-control studies [8,9,10]. Men with testicular cancer tend to have fewer siblings, which might suggest a reduced fertility in their parents [11,12,13]
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