Endogenous Androgens and Risk of Epithelial Invasive Ovarian Cancer by Tumor Characteristics in the European Prospective Investigation Into Cancer and Nutrition

Int J Cancer. 2015 Jan 15;136(2):399-410. doi: 10.1002/ijc.29000. Epub 2014 Jun 16.

Abstract

The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.

Keywords: androstenedione; endogenous androgens; histologic subtype; ovarian carcinoma; type I tumors; type II tumors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androgens / blood*
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Cystadenocarcinoma, Serous / blood*
  • Cystadenocarcinoma, Serous / epidemiology
  • Cystadenocarcinoma, Serous / pathology
  • Europe / epidemiology
  • Fallopian Tube Neoplasms / blood*
  • Fallopian Tube Neoplasms / epidemiology
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / epidemiology
  • Neoplasms, Glandular and Epithelial / pathology
  • Nutritional Status
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / pathology
  • Peritoneal Neoplasms / blood*
  • Peritoneal Neoplasms / epidemiology
  • Peritoneal Neoplasms / pathology
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Sex Hormone-Binding Globulin / metabolism

Substances

  • Androgens
  • Sex Hormone-Binding Globulin