title: Shorter androgen receptor CAG repeat lengths associated with cryptorchidism risk among Hispanic white boys.
abstract: BACKGROUND
  Cryptorchidism is the most frequent congenital malformation among males, the major established risk factor for testicular germ cell tumors, and a presumed infertility risk factor. Androgens are essential for testicular descent, and functional genetic polymorphisms in the androgen receptor gene (AR) are postulated to influence cryptorchidism risk.
  
  
  OBJECTIVE
  The aim of the study was to investigate whether the CAG repeat length polymorphism in exon 1 of the AR is associated with cryptorchidism risk.
  
  
  METHODS
  We conducted a family-based genotype-risk association study employing the transmission disequilibrium test for genotypic variants transmitted on the X-chromosome at a university-affiliated regional children's hospital.
  
  
  METHODS
  We studied 127 Hispanic boys with persistent cryptorchidism and comorbidities described in detail and their biological mothers.
  
  
  METHODS
  Genotypes defined by number of CAG repeats were measured for each member of participating son-mother pairs.
  
  
  METHODS
  Associations between CAG tract length genotype and cryptorchidism risk were estimated using matched-pairs logistic regression.
  
  
  RESULTS
  Cryptorchidism risk was significantly associated with shorter CAG repeats [CAG≤19 vs. CAG≥20, odds ratio (OR)=0.44; 95% confidence interval (CI), 0.23-0.88]. This association was restricted to cryptorchidism with accompanying comorbidities, which was primarily hernia [CAG≤19 vs. CAG≥20, OR=0.35 (95% CI, 0.16-0.78)], and was strongest for bilateral cryptorchidism [CAG≤19 vs. CAG≥20, OR=0.09 (95% CI, 0.010-0.78)].
  
  
  CONCLUSIONS
  Androgen receptor genotypes encoding moderate functional variation may influence cryptorchidism risk, particularly among boys with bilateral nondescent or congenital hernia, and may explain in part the elevated risk of testicular seminoma experienced by ex-cryptorchid boys. Mechanistic research is warranted to examine both classical and nonclassical mechanisms through which androgens may influence risk of cryptorchidism and related conditions.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Children's Hospital Los Angeles, 1441 Eastlake Avenue, MC-9175, Los Angeles, California 90033, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Davis-Dao
authors.forename: Chester J
authors.initials: CJ
authors.lastname: Koh
authors.forename: Brian E
authors.initials: BE
authors.lastname: Hardy
authors.forename: Andy
authors.initials: A
authors.lastname: Chang
authors.forename: Steve S
authors.initials: SS
authors.lastname: Kim
authors.forename: Roger
authors.initials: R
authors.lastname: De Filippo
authors.forename: Andrew
authors.initials: A
authors.lastname: Hwang
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Carroll
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Coetzee
authors.forename: David
authors.initials: D
authors.lastname: Vandenberg
authors.forename: Kimberly
authors.initials: K
authors.lastname: Siegmund
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Cortessis
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003456:Cryptorchidism / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012306:Risk; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen