Faculty Bibliography

Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (> or =30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (> or =50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (> or =40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis

OBJECTIVE: The purpose of this study was to assess the vascular indices generated by 3-dimensional (3D) power Doppler angiography by evaluating the cyclic changes in the vascularity of normal ovaries, including those that were ovulating, nonovulating, and hormonally suppressed. METHODS: In this prospective longitudinal observational study, a cohort of premenopausal regularly menstruating women with no known ovarian disease underwent 3D power Doppler imaging every 2 to 3 days for the duration of 1 menstrual cycle. Four indices were generated: vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and mean grayness. Comparisons of vascularity were made between ovulating, nonovulating, and hormonally suppressed ovaries. Normal ranges were established and graphed longitudinally. RESULTS: Eighteen participants (36 ovaries) ages 28 to 45 years underwent an average of 10 examinations, yielding 368 acquired ovarian volumes for analysis. Seven participants used hormonal contraception. The VI, FI, and VFI were closely correlated (Pearson product moment correlation coefficients, 0.52-0.95). The vascular indices of ovulating ovaries were significantly higher than those of nonovulating ovaries (VI, FI, and VFI, all P < .001), with the largest discrepancies during the luteal phase. Hormonally suppressed ovaries had significantly lower vascularity throughout the cycle (VI, P < .002; FI, P < .001; VFI, P < .007). The vascular indices of all groups appeared to drop during the late follicular period and then rise again. CONCLUSIONS: The VI would suffice as the principal vascular parameter for 3D power Doppler analysis. Preovulatory scans may be more useful for distinguishing pathologic vascularization. Hormonally suppressed ovaries have significantly lower vascularity throughout the cycle. Normal-appearing ovaries with vascular indices above the normal ranges established by these data may warrant further investigation

STUDY OBJECTIVE: To characterize and compare acceptability of human papillomavirus (HPV) vaccination by Latino parents at an urban medical center in the United States and a community hospital in El Salvador. DESIGN: After reading an information sheet on HPV, 148 subjects at Bellevue Hospital in New York City and 160 subjects at Hospital Nacional de Santa Gertrudis in San Vicente, El Salvador, completed a survey. Results were analyzed using chi-square, Fisher's exact test, and Student's t-tests. RESULTS AND CONCLUSIONS: Parental acceptance of HPV vaccination was higher in a sample of Salvadoran subjects than in a sample of U.S. Latinas (P<0.001 for daughters and sons). Reasons for objecting to HPV vaccination differ in the two locations. There are important differences between Salvadoran and U.S. subjects. Salvadorans are more accepting of HPV vaccination, and parental acceptance is unlikely to be a barrier to widespread vaccination in El Salvador. Targeted educational materials are needed in both locations

BACKGROUND: It has been proposed that a shift toward 2-hydroxyestrone from 16alpha-hydroxyestrone metabolic pathway may be inversely associated with breast cancer risk because 2-hydroxyestrone is thought to be less genotoxic and estrogenic than 16alpha-hydroxyestrone. METHODS: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2-hydroxyestrone:16alpha-hydroxyestrone ratio in a case-control study on premenopausal women nested within a prospective cohort the New York University Women's Health Study. The serum levels of 2-hydroxyestrone and 16alpha-hydroxyestrone were measured in 377 incident premenopausal breast cancer cases and 377 premenopausal controls, who were matched on age at enrollment, number and dates of blood donations, and day and phase of menstrual cycle. RESULTS: Overall, no significant associations were observed between breast cancer risk and serum levels of 2-hydroxyestrone, 16alpha-hydroxyestrone, or their ratio. The 2-hydroxyestrone:16alpha-hydroxyestrone ratio was positively associated with risk for estrogen receptor-positive breast cancer in the analyses controlling for matching factors. However, the association was attenuated and not significant after adjustment for potential confounders (odds ratio for the highest versus the lowest quartile, 2.15; 95% CI, 0.88-5.27; P(trend) = 0.09). CONCLUSIONS: The results of the current study do not support the hypothesis that a metabolic shift from 16alpha-hydroxyestrone toward 2-hydroxyestrone in premenopausal women is associated with reduced risk for breast cancer. The association between the 2-hydroxy:16alpha-hydroxyestrone ratio and estrogen receptor-positive breast cancer needs to be explored in future studies

There is a growing interest in the role that cancer biomarkers, metastasis-related molecules, and chemokines may play in the development and progression of various cancers. However, few studies have addressed the reliability of such biomarkers in healthy individuals over time. The objective of this study was to investigate the temporal reliability of multiple proteins in serum samples from healthy women who donated blood over successive years. Thirty five, postmenopausal women with two, repeated annual visits, and thirty, premenopausal women with three, repeated annual visits were randomly selected among eligible subjects from an existing, prospective cohort. Multiplexing Luminex xMAPTM technology was used to measure the levels of 55 serum proteins representing cancer antigens, chemokines, angiogenic and anti-angiogenic factors, proteases, adipokines, apoptotic molecules, and other markers in these women. The biomarkers with high detection rates (> 60%) and acceptable reliability (intraclass correlation coefficient, ICCs > or = 0.55) using xMAPTM method were: cancer antigens: AFP, CA 15-3, CEA, CA-125, SCC, SAA; growth factors/related molecules: ErbB2, IGFBP-1; proteases and adhesion molecules: MMP-1, 8, 9, sE-selectin, human kallikreins (KLK) 8,10, ICAM-1, VCAM-1, chemokines: fractalkine, MCP-1,2, RANTES, MIP-1alpha, MIP-1beta, Eotaxin, GRO-alpha, IP-10; inhibitors of angiogenesis: angiostatin and endostatin; adipokines leptin and resistin; apoptotic factor: Fas, and other proteins mesothelin, myeloperoxidase (MPO), and PAI-1. The rest of the biomarkers under investigation either had ICCs less than 0.55 or had low levels of detection (< 60%). These included cancer antigens: CA 19-9, CA 72-4, MICA, S100, TTR, ULBP1, ULBP2, ULBP3; proteases: MMP 2, 3, 7, 12, 13; chemokines: MCP-3, MIF, MIG; adipokines: leptin and resistin; apoptotic factors: FasL, DR5, Cyfra 21-1; and inhibitors of angiogenesis and other markers: thrombospondin and heat shock protein (HSP) 27. In conclusion, 34 out of the 55 biomarkers investigated were present in detectable levels in > 60% of the samples, and with an ICC > or = 0.55, indicating that a single serum measurement can be used in prospective epidemiological studies using the xMAPTM method

Observational epidemiologic studies and randomized trials have reported a protective effect of oral hormonal replacement therapy on risk of colorectal cancer. Only one previous prospective study, the Women's Health Initiative Observational Study, has reported on the relationship between endogenous hormones and incident colorectal cancer. Contrary to expectation, the investigators found that women with higher circulating estradiol levels were at increased risk of developing colorectal cancer. We conducted a case-control study nested within the New York University Women's Health Study prospective cohort to evaluate the association between endogenous levels of estrone, estradiol, and sex hormone-binding globulin (SHBG) with risk of colorectal cancer. We measured hormones and SHBG in serum samples collected at enrollment from a total of 148 women who subsequently developed colorectal cancer and 293 matched controls. Circulating estrone levels were positively associated with risk of colorectal cancer: The odds ratio for the highest versus lowest quartile of estrone was 1.8 (95% confidence interval, 1.0-3.3). We found a nonsignificant inverse association between SHBG and colorectal cancer, which disappeared after adjusting for body mass index. We did not find an association between estradiol and colorectal cancer risk, but we cannot rule out a potential association because of substantial laboratory error in the measurement. Our results suggest that endogenous estrone is associated with increased risk of colorectal cancer in postmenopausal women

BACKGROUND: In most studies, circulating biomarkers are usually assessed from a single sample, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested although it may not be valid for all biomarkers. The objective of this study was to investigate the temporal reproducibility of a panel of cytokines and growth factors. METHODS: Thirty-five postmenopausal women with two annual visits and 30 premenopausal women with three annual visits were randomly selected from the participants in an existing prospective cohort. A total of 23 serum cytokines, nine growth factors and C-reactive protein (CRP) were measured using the Luminex xMap technology. In addition, for eight biomarkers, regular and high sensitivity (hs) assays were compared. RESULTS: The biomarkers with adequate (>60%) detection rates and acceptable (> or =0.55) intra-class correlation coefficients (ICCs) were: hsIL-1beta, IL-1RA, hsIL-2, hsIL-4, hsIL-5, hsIL-6, hsIL-10, IL-12p40, hsIL-12p70, hsTNF-alpha, TNF-R1, TNF-R2, CRP, HGF, NGF, and EGFR. The remaining biomarkers either had low temporal reproducibility or were undetectable in more than 40% of samples. CONCLUSIONS: The results suggest that 16 of the 41 biomarkers measured with Luminex technology showed sufficient sensitivity and temporal reproducibility in sera

Abstract Objective: Women with risk factors for diabetes are screened early in pregnancy. At our institution we obtain a GCT (glucose challenge test) at first prenatal visit. We sought to compare pregnancy outcomes in women who were diagnosed with GDM early in pregnancy with those diagnosed at the standard 24-28 weeks' gestation. Methods: An inner city population receiving prenatal care from August 2003 to May 2007 participated in the study. Patients were screened during the first trimester when able (group 1) or during the standard 24-28 weeks' gestation (group 2). Patient demographics, maternal and neonatal outcome data were collected and analyzed. Results: Of 340 GDM patients identified, 99 were diagnosed early and 241 at the standard time. Eighty per cent of group 2 were treated with diet alone and 20% required pharmacological therapy. Fifty per cent of group 1 were treated with diet and 45% with pharmacological therapy (P<0.001). Comparison between the early and late diagnosis groups for preterm delivery and hypertensive disorders were statistically non-significant. Cesarean delivery was 45% in group 1 and 24% in group 2. Both macrosomia (13% vs. 6%) and large-for-gestational-age (18% vs. 6%) was statistically higher in the early GTT group. Conclusion: The adverse perinatal outcome is significantly higher in the early diagnosis group despite early identification and management implying greater severity of GDM