A Prospective Study of Gynecological Cancer Risk in Relation to Adiposity Factors: Cumulative Incidence and Association with Plasma Adipokine Levels

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Findings</p><p>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/m², 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.</p><p>Conclusion</p><p>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.</p></div

Box plot describing plasma adipokine levels in relation to gynecological cancers.

<p><b>A.</b> Leptin levels in uterine corpus cancer cases (UCC, n = 20), ovarian cancer cases (OVC, n = 20) and their respective age-menopause–matched controls (n = 120 and 120, respectively). <b>B.</b> Adiponectin levels in uterine corpus cancer cases (n = 20), ovarian cancer cases (n = 20) and their respective age-menopause–matched controls (n = 120 and 120, respectively). *<i>p</i><0.05 and ***<i>p</i><0.001 vs. controls after adjusting for age, alcohol intake (for UCC model only), and years of endogenous estrogen exposure. Adipokine variables were log-transformed before the analysis for significance test.</p

Baseline characteristics of 11,258 study subjects by gynecological cancer and without the cancers.

<p>UCC: Uterine corpus cancer; OVC: Ovarian cancer.</p><p>Triglyceride value is given as median (interquartile range), and the other values are given as mean±SD or number (%).</p>a<p>Age-adjusted <i>p</i>-value <0.05, compared with the participants without the cancers.</p

Hazard ratio estimates of sociodemographic, adiposity and reproductive factors by gynecologic cancer for the 11,258 study subjects, 1991–2011.

a<p>Hazard ratio (HR) and confidence interval (CI) were derived from Cox proportional hazard models using attained age during follow-up as the time axis and stratification of birth cohort in 5-year calendar periods. N.A.: not available.</p><p>*<i>p</i><0.05; **<i>p</i><0.01; ***<i>p</i><0.001.</p

Multivariate model of risk factors for gynecological cancer for the 11,258 study subjects, 1991–2011.

a<p>Hazard ratio (HR) and confidence interval (CI) were derived from Cox proportional hazard models using attained age during follow-up as the time axis and stratification of birth cohort in 5-year calendar periods.</p>b<p>PAF: population attributable fraction of total cases that would be reduced if a modifiable risk factor were eliminated from the study cohort. The formula for PAF estimation is presented in Methods section. N.A.: not applied.</p

Incidences of uterine corpus cancer (UCC) and ovarian cancer (OVC) by age groups among 11,258 participants out of the CBCSP-HVP cohort, 1991–2011.

a<p>IR: incidence rate.</p

Visualization 2: Optically driven full-angle sample rotation for tomographic imaging in digital holographic microscopy

3-D tomographic reconstruction of the yeast Originally published in Optics Letters on 01 April 2017 (ol-42-7-1321

Baseline characteristics of the 53,293 women with LSIL cytology in this study and the management and incidence of subsequent CIN3+ lesions.

<p>Baseline characteristics of the 53,293 women with LSIL cytology in this study and the management and incidence of subsequent CIN3+ lesions.</p

Multivariate analysis of the risk for subsequent CIN3+ lesions after adjusting for age and screening interval in 53,293 women with LSIL cytology and/or CIN1 pathology.

<p>Multivariate analysis of the risk for subsequent CIN3+ lesions after adjusting for age and screening interval in 53,293 women with LSIL cytology and/or CIN1 pathology.</p

Baseline characteristics of the 53,293 women with LSIL cytology in this study and the management and incidence of subsequent CIN3+ lesions.

<p>Baseline characteristics of the 53,293 women with LSIL cytology in this study and the management and incidence of subsequent CIN3+ lesions.</p