Kepher H. Makambi

Dietary patterns and breast cancer risk in women participating in the Black Women’s Health Study

BACKGROUND No studies have examined dietary patterns and breast cancer risk in a large cohort of African American women. OBJECTIVE We investigated the association between dietary patterns and breast cancer risk in the Black Womens Health Study. DESIGN This is a prospective cohort study of 50,778 participants followed biennially from 1995 through 2007. During 443,742 person-years of follow-up, 1094 incident cases of breast cancer were identified. Factor analysis was used to derive food patterns based on 69 food variables. We used Cox regression models to obtain incident rate ratios (IRRs) for breast cancer in relation to quintiles of each of the 2 dietary patterns, with adjustment for other breast cancer risk factors. RESULTS Through factor analysis, we identified 2 dietary patterns: Western (refined grains, processed meat, and sweets) and prudent (whole grains, vegetables, fruit, and fish). The prudent diet was weakly associated with lower breast cancer risk overall; P for trend = 0.06. In analyses stratified by body mass index (BMI; in kg/m(2)), the prudent dietary pattern was associated with a significantly lower risk of breast cancer in women with a BMI <25 (IRR: 0.64; 95% CI: 0.43, 0.93; P for trend = 0.01). The prudent dietary pattern was also associated with a significantly lower risk of breast cancer in premenopausal women (IRR: 0.70; 95% CI: 0.52, 0.96; P for trend = 0.01), and we found a significant inverse association for the prudent dietary pattern and estrogen receptor-negative breast cancer (IRR: 0.52; 95% CI: 0.28, 0.94; P for trend <0.01). CONCLUSION Our findings suggest that the prudent dietary pattern may protect against breast cancer in some black women.

Steroid hormone levels associated with passive and active smoking

CONTEXT Cigarette tobacco smoke is a potent environmental contaminant known to adversely affect health including fertility and pregnancy. OBJECTIVE To examine the associations between second-hand cigarette tobacco-smoke exposure, or active smoking and serum concentrations of steroid hormones using tandem mass spectrometry. DESIGN Healthy women (18-45 y) from the general community in the Metropolitan Washington, DC were recruited at the follicular stage of their menstrual cycle. Participants were assigned to one of three study groups: active smokers (N=107), passive smokers (N=86), or non-smokers (N=100). Classifications were based on a combination of self-reporting and serum cotinine concentrations. METHODS Serum androgens, estrogens, progestins, androstenedione, aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 11-deoxycortisol and 25-hydroxy-vitamin D3 (25-OHVitD3) and cotinine were measured by isotope dilution tandem mass spectrometry (LC/MS/MS) (API-5000). Kruskal-Wallis tests were used to assess median differences among the three groups, with Dunns multiple comparison test for post hoc analysis. RESULTS Serum estrone, estradiol, and estriol concentrations were lower in active and passive smokers than in non-smokers. The three study groups differed significantly in serum concentrations of 16-OHE1, aldosterone and 25-OHVitD3, as well as in the ratios of many of the steroids. Pair-wise comparison of the groups demonstrated significant differences in hormone concentrations between (i) smokers and non-smokers for aldosterone: (ii) passive smokers and non-smokers for aldosterone, progesterone and estriol. Moreover, for smokers and passive smokers, there were no significant differences in these hormone concentrations. CONCLUSIONS Smoke exposure was associated with lower than normal median steroid hormone concentrations. These processes may be instrumental in explaining some adverse effects of tobacco smoke on female health and fertility.

Meta-analysis of endoscopic versus sublabial pituitary surgery†‡

To determine whether the endoscopic or sublabial transseptal transsphenoidal approach for pituitary surgery has superior outcomes or decreased complication rates.

MicroRNA-9 as Potential Biomarker for Breast Cancer Local Recurrence and Tumor Estrogen Receptor Status

MicroRNAs (miRs) are small, non-protein coding transcripts involved in many cellular functions. Many miRs have emerged as important cancer biomarkers. In the present study, we investigated whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR). Sixty-eight women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this study. Breast cancer patients with LR and those without LR were matched on year of surgery, age at diagnosis, and type of surgery. Candidate miRs were identified by screening the expression levels of 754 human miRs using miR arrays in 16 breast tumor samples from 8 cases with LR and 8 cases without LR. Eight candidate miRs that showed significant differences between tumors with and without LR were further verified in 52 tumor samples using real-time PCR. Higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 0.02). The AUCs (Area Under Curve) of receiver operating characteristic (ROC) curves of miR-9 for all tumors and ER positive tumors are 0.68 (p = 0.02) and 0.69 (p = 0.02), respectively. In ER positive cases, Kaplan-Meier analysis showed that patients with lower miR-9 levels had significantly better 10-year LR-free survival (67.9% vs 30.8%, p = 0.02). Expression levels of miR-9 and another miR candidate, miR-375, were also strongly associated with ER status (p<0.001 for both). The potential of miR-9 as a biomarker for LR warrants further investigation with larger sample size.

Quantitative Liquid Chromatography-Mass Spectrometry-Multiple Reaction Monitoring (LC-MS-MRM) Analysis of Site-specific Glycoforms of Haptoglobin in Liver Disease

Development of liver disease is associated with the appearance of multiply fucosylated glycoforms of haptoglobin. To analyze the disease-related haptoglobin glycoforms in liver cirrhosis and hepatocellular carcinoma, we have optimized an LC-MS-multiple reaction monitoring (MRM) workflow for glycopeptide quantification. The final quantitative analysis included 24 site-specific glycoforms generated by treatment of a tryptic digest of haptoglobin with α(2–3,6,8)-neuraminidase and β(1–4)-galactosidase. The combination of LC-MS-MRM with exoglycosidase digests allowed resolution of isobaric glycoforms of the haptoglobin-T3 glycopeptide for quantification of the multiply fucosylated Lewis Y-containing glycoforms we have identified in the context of liver disease. Fourteen multiply fucosylated glycoforms of the 20 examined increased significantly in the liver disease group compared with healthy controls with an average 5-fold increase in intensity (p < 0.05). At the same time, two tri-antennary glycoforms without fucoses did not increase in the liver disease group, and two tetra-antennary glycoforms without fucoses showed a marginal increase (at most 40%) in intensity. Our analysis of 30 individual patient samples (10 healthy controls, 10 cirrhosis patients, and 10 hepatocellular carcinoma patients) showed that these glycoforms were substantially increased in a small subgroup of liver disease patients but did not significantly differ between the groups of hepatocellular carcinoma and cirrhosis patients. The tri- and tetra-antennary singly fucosylated glycoforms are associated with a MELD score and low platelet counts (p < 0.05). The exoglycosidase-assisted LC-MS-MRM workflow, optimized for the quantification of fucosylated glycoforms of haptoglobin, can be used for quantification of these glycoforms on other glycopeptides with appropriate analytical behavior.

An assessment of the CES-D scale factor structure in black women: The Black Women's Health Study

This study investigates the dimensional structure of the Center for Epidemiologic Studies Depression (CES-D) scale in US Black women with and without history of cancer via single-group and multi-group analyses. The CES-D questionnaire was administered in 1999 to 50,774 black women who are participants in the Black Womens Health Study (BWHS). For our analysis, we utilized a group of 690 women with a history of at least one of the three types of cancer (breast cancer, colon cancer or lung cancer) and an age-matched group of 1,380 healthy women with no history of any cancer or other chronic conditions including myocardial infarctions, stroke, angina, diabetes, lupus, and sarcoidosis. Three a priori hypothesized models were tested via confirmatory factor analysis: single-, three- and four-factor structures. The four-factor model provided the best fit and remained largely invariant across the groups when tested via multi-group comparisons. Two internal consistency measures of the scale (Cronbachs alpha coefficient and split-half coefficient) were also shown to be satisfactory. We concluded that the CES-D scale is appropriate for use in black women regardless of their cancer status.

Molecular Breast Cancer Subtypes in Premenopausal African-American Women, Tumor Biologic Factors and Clinical Outcome

IntroductionBreast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women.MethodsA retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998–2005, was performed.ResultsThe luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01).The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31).ConclusionThe high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.

Impact of Perceived Racial Discrimination on Health Screening in Black Women

Perceived discrimination has been shown to be related to health screening behavior. The present study examines the effect of discrimination on cancer screening among women in the Black Womens Health Study. Five self-report items measured discrimination in everyday life and three items measured experiences of major discrimination. Logistic regression was used to test associations of discrimination with Pap smear, mammography, or colonoscopy utilization. At the start of follow-up, 88.8% had a Pap smear in the previous year, 52.7% had a mammogram, and 20.0% had received a colonoscopy. Both everyday and major discrimination were associated with not having received a Pap smear, even after adjusting for other variables. Discrimination was not associated with mammography or colonoscopy utilization. In conclusion, perceived everyday and major discrimination is associated with poorer utilization of Pap smears for cervical cancer screening among Black women.

Small sample properties of tests on homogeneity in one—way Anova and Meta—analysis

In the present Monte Carlo study, the empirical Type I error properties and power of several statistics for testing the homogeneity hypothesis in a one—way classification are examined in the case of small sample sizes. We compared these tests under several scenarios: normal populations under heterogeneous variances, nonnormal populations under homogeneous variances, nonnormal populations under heterogeneous variances, balanced and unbalanced sample sizes, and increasing number of populations. Overall, none of the tests considered is uniformly dominating the others. Under normality and variance heterogeneity, the Brown—Forsythe and the Welch test perform well over a wide range of parameter configurations, the modified Brown-Forsythe test by Mehrotra keeps generally the level, but other tests may also perform well, depending on the constellation of the parameters under study. The Welch test becomes liberal when the sample sizes are small and the number of populations is large. We propose a modified version of Welch’s test that keeps the nominal level in these cases. With the understanding that methods are unacceptable if they have Type I error rates that are too high, only the testing procedure associated with the modified Brown-Forsythe test can be recommended both for normal and nonnormal data. Under normality, the modified Welch test can also be recommended.

Use of multivitamins, folic acid and herbal supplements among breast cancer survivors: the black women's health study

BackgroundComplementary and alternative medicine (CAM) use, including herbals and multivitamin supplements, is quite common in the U.S., and has been shown to be highest in breast cancer survivors. However, limited data are currently available for CAM usage among African Americans. Thus, we sought to determine the prevalence of multivitamins, folic acid and herbal supplement usage in African American breast cancer survivors, and to compare the characteristics of users and nonusers.MethodsA cohort study of breast cancer survivors, who completed the 1999 Black Womens Health Study questionnaire and self-reported having been diagnosed with breast cancer between 1995 and 1999, comprised the study population. In this study, the intake of natural herbs, multivitamins and folic acid at least three days per week within the past two years was used as a proxy for typical usage of this complimentary alternative medicine (CAM) modality.ResultsA total of 998 breast cancer survivors were identified. Overall, 68.2% had used either herbals or multivitamin supplements or both. The three most frequently used herbals were garlic (21.2%), gingko (12.0%), and echinacea (9.4%). The multivariate analysis determined that single marital status (OR = 1.58; 95%CI: 1.04-2.41), and alcohol consumption of 1-3 drinks per week (OR = 1.86, 95%CI: 1.28-2.68) were significantly associated with increased herbal use. Multivitamin use was significantly lower among obese women (OR = 0.66, 95%CI: 0.46-0.94) and current smokers (OR = 0.53, 95%CI: 0.34-0.82).ConclusionsA significant number of African American breast cancer survivors are using herbals and multivitamins as CAM modality. Additional research is needed to understand the impact of herbals and multivitamins in African American breast cancer survivors.