Intrauterine factors and risk of nonepithelial ovarian cancers.

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.