title: Subfertility and Risk of Testicular Cancer in the EPSAM Case-Control Study.
abstract: OBJECTIVE
  It 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  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. 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Chiara
authors.identifier: http://orcid.org/0000-0002-2597-4990
authors.initials: C
authors.lastname: Grasso
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zugna
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Fiano
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Nena
authors.initials: N
authors.lastname: Robles Rodriguez
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Maule
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gillio-Tos
authors.affiliation: Medical Oncology Division 1, University Hospital "Città della Salute e della Scienza", Turin, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Ciuffreda
authors.affiliation: Medical Oncology Division 1, University Hospital "Città della Salute e della Scienza", Turin, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lista
authors.affiliation: Department of Cancer Screening and Unit of Cancer Epidemiology, WHO Collaborative Center for Cancer Early Diagnosis and Screening, CPO Piedmont and University Hospital "Città della Salute e della Scienza", Turin, Italy.
authors.forename: Nereo
authors.initials: N
authors.lastname: Segnan
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.affiliation: Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Richiardi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005191:Family Characteristics; D006801:Humans; D007248:Infertility, Male / Q000453:epidemiology* / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics; D019089:Stem Cell Factor / Q000235:genetics*; D011795:Surveys and Questionnaires; D013736:Testicular Neoplasms / Q000453:epidemiology* / Q000235:genetics
chemical_list: D019089:Stem Cell Factor