Relationship Between Plasma Glucose Levels and Malignant Uterine Cervical Neoplasias

Background There is a direct correlation between glycemic load and the risk of developing many malignant neoplasms. Aims The aim of this study was to determine the plasma glucose levels in women with cervical cancer. Methods The study included 177 women with anatomopathologically diagnosed uterine cervical cancer (stages 0–IV) treated between 1980 and 2008 at the Gynecology and Obstetrics outpatient service of the UFTM, Brazil. The plasma glucose levels of all patients were assayed at the time of diagnosis and correlated with tumor staging. Results We statistically compared the plasma glucose levels of group 1 (cervical intraepithelial neoplasia 2–3), group 2 (stage I–II), group 3 (stage III–IV), and group 4 (control group: leiomyomas). Patient groups with poor prognosis (groups 2 and 3) showed significantly higher plasma glucose levels ( P 90 mg/dl showed CIN versus I/II: P = 0.0753; OR = 2.018; (95% CI: 0.9236 to 4.410) and CIN versus III/IV: P = 0.0975; OR = 2.400; (95% CI: 0.8335 to 6.911). Conclusion We observed an association between high plasma glucose levels and cervical cancer cases with poor prognoses. Plasma glucose tests should be routinely used as additional prognostic parameters in patients with cervical neoplasias

Reliability of follicle-stimulating hormone measurements in serum

BACKGROUND: Follicle-stimulating hormone (FSH), a member of gonadotropin family, is critical for follicular maturation and ovarian steroidogenesis. Serum FSH levels are known to fluctuate during different phases of menstrual cycle in premenopausal women, and increase considerably after the menopause as a result of ovarian function cessation. There is little existing evidence to guide researchers in estimating the reliability of serum FSH measurements. The objective of this study was to assess the reliability of FSH measurement using stored sera from an ongoing prospective cohort – the NYU Women's Health Study. METHODS: Sixty healthy women (16 premenopausal, 44 postmenopausal), who donated at least two blood samples at approximately 1-year intervals were studied. An immunoradiometric assay using a sandwich monoclonal antibodies technique was used to measure FSH levels in serum. RESULTS: The reliability of a single log-transformed FSH measurement, as determined by the intraclass correlation coefficient, was 0.70 for postmenopausal women (95% confidence interval (CI), 0.55–0.82) and 0.09 for premenopausal women (95% CI, 0–0.54). CONCLUSIONS: These results suggest that a single measurement is sufficient to characterize the serum FSH level in postmenopausal women and could be a useful tool in epidemiological research. For premenopausal women, however, the reliability coefficient was low, suggesting that a single determination is insufficient to reliably estimate a woman's true average serum FSH level and repeated measurements are desirable

Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies

Insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), and insulin-like growth factor binding protein-3 (IGFBP-3) were measured in frozen serum samples from 1051 men with cancer and 3142 controls in a nested case–control study from the British United Provident Association (BUPA) study cohort and associations with 14 cancers were examined, including prostate, colorectal, and lung. A meta-analysis of studies on these three cancer sites was also conducted. In the meta-analysis the odds ratio between the highest quartile IGF-1 group and the lowest quartile group was 1.31 (95% confidence interval (CI): 1.03–1.67) for prostate, 1.37 (1.05–1.78) for colorectal and 1.02 (0.80–1.31) for lung cancer, and for IGF-2 it was 0.72 (0.36–1.44) for prostate and 1.95 (1.26–3.00) for colorectal cancer. Results from the BUPA study were consistent with the estimates from the other studies. There were no statistically significant associations with IGFBP-3 and any of the cancer sites considered. Our results suggest that IGF-1, IGF-2, and IGFBP-3 measurements have no value in cancer screening, although IGF-1 and IGF-2 may be of aetiological significance in relation to colorectal and prostate cancer

Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer.

BACKGROUND: Sex steroid hormones have been proposed to play a role in the development of non-epithelial ovarian cancers (NEOC) but so far no direct epidemiological data are available.METHODS: A case-control study was nested within the Finnish Maternity Cohort, the world's largest bio-repository of serum specimens from pregnant women. Study subjects were selected among women who donated a blood sample during a singleton pregnancy that led to the birth of their last child preceding diagnosis of NEOC. Case subjects were 41 women with sex-cord stromal tumors (SCST) and 21 with germ cell tumors (GCT). Three controls, matching the index case for age, parity at the index pregnancy, and date at blood donation were selected (n=171). Odds ratios (OR) and 95% confidence intervals (CI) associated with concentrations of testosterone, androstenedione, 17-OH-progesterone, progesterone, estradiol and sex hormone binding globulin (SHBG) were estimated through conditional logistic regression.RESULTS: For SCST, doubling of testosterone, androstenedione and 17-OH-progesterone concentrations were associated with about 2-fold higher risk of SCST [ORs and 95% CI of 2.16 (1.25-3.74), 2.16 (1.20-3.87), and 2.62 (1.27-5.38), respectively]. These associations remained largely unchanged after excluding women within 2, 4 or 6 years lag-time between blood donation and cancer diagnosis. Sex steroid hormones concentrations were not related to maternal risk of GCT.CONCLUSIONS: This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. Impact: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC

Circulating prolactin levels and risk of epithelial ovarian cancer

Purpose: Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown. Methods: We conducted a nested case-control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls. Results: Prolactin levels were significantly lower among post- versus pre-menopausal women, parous versus nulliparous women, and past versus never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case-control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (ORQ4vsQ1 1.56, 95 % CI 0.94, 2.63, p trend 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood 655 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI 6525 kg/m2 (ORQ4vsQ1 3.10, 95 % CI 1.39, 6.90), but not for women with BMI <25 kg/m2 (OR Q4vsQ1 0.81, 95 % CI 0.40, 1.64). Conclusions: Our findings suggest that prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk

The challenge of measuring circulating estradiol at low concentrations

Demand for measuring estradiol at low concentrations is increasing, and the widely used 'direct' radioimmunoassays that do not require a preliminary organic purification step may be inadequate in patient care because of their limited accuracy. In observational epidemiology, however, the main concern is to obtain a correct ranking of individuals' hormone concentration relative to the true level (as determined through a 'gold standard'). Despite differences in the absolute scale of measured and true concentrations, correct ranking will permit calculation of unbiased estimates of hormone–disease associations. In prospective studies, the major concerns are the limited volume of often irreplaceable specimens and the need to perform a large number of assays within a reasonable period of time. Organic purification is often not feasible because of sample volume requirements and logistic difficulties, and so the development of accurate, rapid and inexpensive methods to measure sex steroids at low concentrations would represent a valuable new research tool for both clinicians and epidemiologists

Body size in early life and risk of epithelial ovarian cancer: results from the Nurses' Health Studies

Adult body mass index (BMI) has been associated with ovarian cancer risk, but few studies have examined body size earlier in life. We prospectively examined associations of body fatness at ages 5 and 10, BMI at age 18, height, and birthweight with risk of epithelial ovarian cancer in the Nurses' Health Study (NHS: 110 311 women, 735 cases) and Nurses' Health Study II (NHSII: 113 059 women, 137 cases). Cox proportional hazards regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). There was a weak inverse association between average body fatness at ages 5 and 10 and risk in the NHS (RR for heaviest vs most lean=0.81, 95% CI: 0.53–1.24, P for trend=0.04) and a nonsignificant positive association in the NHSII (RR=2.09, 95% CI: 0.98–4.48, P for trend=0.10), possibly due to differences in age and menopausal status. Height was positively associated with risk in both cohorts (RR for ⩾1.75 vs <1.6 m=1.43, 95% CI: 1.05–1.96, P for trend=0.001). Body mass index at the age of 18 years and birthweight were not associated with risk. Further research should examine the biological mechanisms underlying the observed associations

Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study

BACKGROUND: The sex hormone-binding globulin (SHBG) is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer. METHODS: The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms (SNPs) in SHGB and five in ATP1B2 were selected to capture most common variation in this region. RESULTS: None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259) and -67G>A 5'UTR (rs1799941). However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG. CONCLUSION: These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk

Circulating soluble Fas levels and risk of ovarian cancer

BACKGROUND: Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. METHODS: The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umeå (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. RESULTS: Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4 – 10.2) and in controls (median, 6.8 ng/mL; range, 4.5 – 10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42 – 1.82). CONCLUSION: The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer