Faculty Bibliography

PURPOSE: The aim of the study is to determine the reliability during a 2-year period of several newly developed iron-related assays to assess their potential for use in prospective epidemiologic studies. METHODS: We assessed the temporal reliability of several iron-related assays by using three serum samples collected at yearly intervals from 50 postmenopausal participants in a large prospective study. RESULTS: We observed high reliability coefficients for ferritin (0.78; 95% confidence interval [CI], 0.67-0.86), soluble transferrin receptor (sTfR; 0.79; 95% CI, 0.69-0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62-0.83), and hepcidin (0.89; 95% CI, 0.84-0.94). In a subset of 30 women, lower reliability was observed for serum iron (0.50; 95% CI, 0.29-0.70), unsaturated iron-binding capacity (0.55; 95% CI, 0.34-0.73), total iron-binding capacity (0.60; 95% CI, 0.40-0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22-0.65). The reliability of anti-5-hydroxymethyl-2'-deoxyuridine autoantibody titers, a biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought to impact disease risk, was very high (0.97, 95% CI, 0.5-0.99). CONCLUSIONS: Our results show that some newly developed iron-related assays could be useful tools to assess iron-disease associations in prospective cohorts that collect a single blood sample

BACKGROUND: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy. METHODS: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II. CONCLUSIONS: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer

Epidemiologic evidence suggests that a full-term pregnancy may affect maternal risk of breast cancer later in life. The objective of this cross-sectional study was to compare circulating levels of maternal hormones affecting breast differentiation (human chorionic gonadotropin and prolactin) and proliferation [alpha-fetoprotein, insulin-like growth factor I (IGF-I), and estradiol] between women at a low to moderate risk (Asians and Hispanics), as compared with women at a high risk for breast cancer (Caucasians and African-Americans). Between May 2002 and December 2004, a total of 586 pregnant women were approached during a routine prenatal visit. Among them, 450 women (206 Caucasian, 126 Asian, 88 Hispanic, and 30 African-American) met the inclusion criteria and signed the informed consent. Only singleton pregnancies were considered. Blood samples were drawn during the second trimester of pregnancy. Laboratory analyses were done using the IMMULITE 2000 immunoassay system. Gestational age standardized mean levels of estradiol, IGF-I, and prolactin were significantly higher in Hispanic women compared with Caucasian women. Mean concentration of IGF-I was significantly higher in African-American women compared with Caucasian and Asian women. No significant differences in pregnancy hormone levels were observed between Caucasian and Asian (predominantly second-generation Chinese) women in this study. Irrespective of ethnicity, women who had their first pregnancy had substantially higher mean levels of alpha-fetoprotein, human chorionic gonadotropin, estradiol, and prolactin compared with women who previously had at least one full-term pregnancy. These data suggest that circulating pregnancy hormone levels may explain some of the ethnic differences in breast cancer risk

Extra-amniotic saline infusion (EASI) via a Foley catheter has been thought to be comparable in efficacy to other induction and cervical ripening methods. This study examines the risk of cesarean delivery associated with EASI compared with spontaneous labor and other methods of cervical ripening. A retrospective cohort study based upon deliveries at Bellevue Hospital Center from August 2000 to December 2002 was conducted. Three groups were identified: EASI, other methods of induction such as prostaglandins and oxytocin administration, and spontaneous labor. Pairwise comparisons were performed using analysis of variance and multivariate logistic regression analysis to control for confounding variables. There were 625 charts evaluated: including 171 with EASI, 190 with other induction methods, and 264 with spontaneous labor. The rates of cesarean section were 33.9%, 17.9%, and 7.2%, respectively. When compared with spontaneous labor, there was a higher risk of cesarean delivery for subjects induced with other methods (adjusted odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.5; P < 0.001), and for those induced with EASI (adjusted OR, 5.5; 95% CI, 3.1 to 9.9; P < 0.001). When EASI was compared with other methods of induction, the risk of cesarean delivery was still increased (adjusted OR, 2.3; 95% CI, 1.4 to 3.8; P = 0.001). EASI is associated with an increased risk of cesarean delivery compared with spontaneous labor and other methods of cervical ripening

OBJECTIVE: We investigated whether levels of annexin A5 (AnxA5), AnxA5 anticoagulant activity and binding, and anti-AnxA5 antibodies might be altered in women with previous histories of recurrent spontaneous pregnancy losses (RSPL) when tested during pregnancy. STUDY DESIGN: Ninety pregnant women with histories of 3 or more RSPL (cases) and 150 women without adverse pregnancy histories (controls) were assayed for these AnxA5 parameters. RESULTS: There were no significant differences between cases and controls in AnxA5 levels (median, 23.1 ng/mL [range, 2.1-201.1 ng/mL] vs 19.7 ng/mL [2.1-151.5 ng/mL]; P = .20), AnxA5 anticoagulant activity (183% [101%-236%] vs 168% [128%-256%]; P = .39) and binding (6.0 ng/aliquot PL [2.1-19.5 ng/aliquot PL) vs 6.1 ng/aliquot PL [1.6-16.8 ng/aliquot PL]; P = .72), and anti-AnxA5 antibody levels. CONCLUSIONS: AnxA5 parameters do not distinguish between cases and controls when tested during pregnancy. The pregnant state itself appears to be associated with altered levels of AnxA5 parameters