Joint associations between genetic variants and reproductive factors in glioma risk among women

Am J Epidemiol. 2011 Oct 15;174(8):901-8. doi: 10.1093/aje/kwr184. Epub 2011 Sep 13.

Abstract

In a pooled analysis of 4 US epidemiologic studies (1993-2001), the authors evaluated the role of 5 female reproductive factors in 357 women with glioma and 822 controls. The authors further evaluated the independent association between 5 implicated gene variants and glioma risk among the study population, as well as the joint associations of female reproductive factors (ages at menarche and menopause, menopausal status, use of oral contraceptives, and menopausal hormone therapy) and these gene variants on glioma risk. Risk estimates were calculated as odds ratios and 95% confidence intervals that were adjusted for age, race, and study. Three of the gene variants (rs4295627, a variant of CCDC26; rs4977756, a variant of CDKN2A and CDKN2B; and rs6010620, a variant of RTEL1) were statistically significantly associated with glioma risk in the present population. Compared with women who had an early age at menarche (<12 years of age), those who reported menarche at 12-13 years of age or at 14 years of age or older had a 1.7-fold higher risk and a 1.9-fold higher risk of glioma, respectively (P for trend = 0.009). Postmenopausal women and women who reported ever having used oral contraceptives had a decreased risk of glioma. The authors did not observe joint associations between these reproductive characteristics and the implicated glioma gene variants. These results require replication, but if confirmed, they would suggest that the gene variants that have previously been implicated in the development of glioma are unlikely to act through the same hormonal mechanisms in women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Age of Onset
  • Aged
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / etiology
  • Brain Neoplasms / genetics*
  • Contraceptives, Oral, Hormonal / therapeutic use
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Helicases / genetics
  • Female
  • Genetic Variation
  • Glioma / epidemiology
  • Glioma / etiology
  • Glioma / genetics*
  • Hormone Replacement Therapy / statistics & numerical data
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Menarche*
  • Menopause*
  • Middle Aged
  • Risk Factors
  • United States / epidemiology

Substances

  • CCDC26 protein, human
  • CDKN2B protein, human
  • Contraceptives, Oral, Hormonal
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Intracellular Signaling Peptides and Proteins
  • RTEL1 protein, human
  • DNA Helicases