title: Intrauterine factors and risk of nonepithelial ovarian cancers.
abstract: OBJECTIVE
  The majority of ovarian tumors in girls and young women are nonepithelial in origin. The etiology of nonepithelial ovarian tumors remains largely unknown, and intrauterine exposures may play an important role. We examined the association of perinatal factors with risk of nonepithelial ovarian tumors in girls and young women.
  
  
  METHODS
  National cohort study of 1,536,057 women born in Sweden during 1973-2004 and followed for diagnoses of nonepithelial ovarian tumors through 2009 (attained ages 5-37 years). Perinatal and maternal characteristics and cancer diagnoses were ascertained using nationwide health registry data.
  
  
  RESULTS
  147 women were diagnosed with nonepithelial ovarian tumors in 31.6 million person-years of follow-up, including 94 with germ cell tumors and 53 with sex-cord stromal tumors. Women born preterm (<37 weeks of gestation) had a significantly increased risk of developing nonepithelial ovarian tumors (adjusted hazard ratio 1.86, 95% CI 1.03-3.37; p=0.04). Histological subgroup analyses showed that preterm birth was associated with increased risk of sex-cord stromal tumors (4.39, 2.12-9.10; p<0.001), but not germ cell tumors (0.68, 0.21-2.15; p=0.51). No significant associations were found with fetal growth, birth order, and maternal age at birth.
  
  
  CONCLUSIONS
  This large cohort study provides the first evidence that preterm birth is a risk factor for developing sex cord-stromal tumors. Ovarian hyperstimulation in response to high gonadotropin levels in preterm girls could mediate disease risk through the proliferative and steroidogenic effects of FSH and LH on granulosa and theca cells, from which most sex-cord stromal tumors are derived.
authors: Department of Health Research and Policy, Stanford University, Stanford, CA, USA. Electronic address: wsieh@stanford.edu.
authors: Weiva
authors: W
authors: Sieh
authors: Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
authors: Kristina
authors: K
authors: Sundquist
authors: Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
authors: Jan
authors: J
authors: Sundquist
authors: Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
authors: Marilyn A
authors: MA
authors: Winkleby
authors: Department of Medicine, Stanford University, Stanford, CA, USA.
authors: Casey
authors: C
authors: Crump
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology*; D010051:Ovarian Neoplasms / Q000453:epidemiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D018312:Sex Cord-Gonadal Stromal Tumors / Q000453:epidemiology*; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
keywords: Germ cell tumors; Gestational age; Nonepithelial ovarian cancers; Perinatal factors; Preterm birth; Sex-cord stromal tumors