A prospective study of gynecological cancer risk in relation to adiposity factors: cumulative incidence and association with plasma adipokine levels

PLoS One. 2014 Aug 12;9(8):e104630. doi: 10.1371/journal.pone.0104630. eCollection 2014.


Background: Associations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers.

Methods: Totally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels.

Findings: There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28-5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08-3.38) were associated with increased UCC risk. High body mass index (BMI ≥ 27 kg/m(2), HR = 2.90, 95% = 1.30-6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates.

Conclusion: We provided evidence that alcohol intake, high triglyceride levels and long endogenous estrogen exposure increase UCC risk, whereas obesity positively predicts OVC risk. Circulating adipokines may mediate the link of adiposity factors to gynecological cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Adiposity*
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Genital Neoplasms, Female / blood
  • Genital Neoplasms, Female / epidemiology*
  • Genital Neoplasms, Female / etiology*
  • Humans
  • Incidence
  • Middle Aged
  • Obesity / complications*
  • Odds Ratio
  • Population Surveillance
  • Prospective Studies
  • Risk
  • Taiwan / epidemiology


  • Adipokines

Grant support

This research was funded by grants from the National Science Council, Executive Yuan (NSC 98-2628-B-002-083-MY3, NSC 98-2811-B-002-054, NSC 99-2811-B-002-187, NSC 100-2811-B-002-144). Additional supports were received from the grants of the National Science Council (NSC 97-2314-B-001-001-MY3, NSC 100-2314-B-001-003-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.