title: Childhood Cancer Risk in the Siblings and Cousins of Men with Poor Semen Quality.
abstract: Poor semen quality is associated with reduced somatic health and increased cancer risk. Infertility and cancer are increasingly being linked by epidemiologists and basic scientists. We sought to identify semen parameters associated with an increased childhood cancer risk in the family members of subfertile men.
  
  
  
  We performed a retrospective cohort study in men from the SHARE (Subfertility Heath and Assisted Reproduction) study who underwent semen analysis between 1994 and 2011. We used fertile population controls from the Utah Population Data Base. Our primary outcome was the risk of any childhood (18 years or younger) cancer in the siblings and cousins of men who underwent semen analysis compared to fertile, age matched controls. Cox proportional hazard regression models were used to test the association between semen quality and childhood cancer incidence.
  
  
  
  We selected 10,511 men with complete semen analysis and an equal number of fertile controls. These men had a total of 63,891 siblings and 327,753 cousins. A total of 170 and 958 childhood cancers were identified in siblings and cousins, respectively. The 3 most common cancers diagnosed in siblings were acute lymphoblastic leukemia in 37, brain cancer in 35 and Hodgkin lymphoma in 15. Oligozoospermia was associated with a twofold increased risk of any childhood cancer and a threefold increased risk of acute lymphoblastic leukemia in the siblings of subfertile men compared to fertile controls (HR 2.09, 95% CI 1.18-3.69 vs HR 3.07, 95% CI 1.11-8.46).
  
  
  
  Siblings of men with oligozoospermia are at increased risk for any-site cancer and acute lymphoblastic leukemia. This suggests a shared genetic/epigenetic insult or an environmental exposure that merits further investigation.
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah. Electronic address: r.anderson@hsc.utah.edu.
authors.forename: Ross E
authors.initials: RE
authors.lastname: Anderson
authors.affiliation: Department of Family and Preventive Medicine and Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Hanson
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah.
authors.forename: William T
authors.initials: WT
authors.lastname: Lowrance
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Redshaw
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah.
authors.forename: Siam
authors.initials: S
authors.lastname: Oottamasathien
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah.
authors.forename: Anthony
authors.initials: A
authors.lastname: Schaeffer
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah.
authors.forename: Erica
authors.initials: E
authors.lastname: Johnstone
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah; Department of Human Genetics, School of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Aston
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah; Department of Human Genetics, School of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Carrell
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cartwright
authors.affiliation: Department of Family and Consumer Studies and Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Smith
authors.affiliation: Division of Urology, Department of Surgery, University of Utah, Salt Lake City, Utah.
authors.forename: James M
authors.initials: JM
authors.lastname: Hotaling
mesh_terms: D000328:Adult; D002648:Child; D015331:Cohort Studies; D005192:Family Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D055101:Semen Analysis
keywords: neoplasms; oligospermia; precursor cell lymphoblastic leukemia-lymphoma; siblings; testis