Julie R. Palmer

General and Abdominal Obesity and Risk of Death among Black Women

BACKGROUND Recent pooled analyses show an increased risk of death with increasing levels of the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 25.0 or higher in populations of European ancestry, a weaker association among East Asians, and no association of an increased BMI with an increased risk of death among South Asians. The limited data available on blacks indicate that the risk of death is increased only at very high levels of BMI (≥35.0). METHODS We prospectively assessed the relation of both BMI and waist circumference to the risk of death among 51,695 black women with no history of cancer or cardiovascular disease who were 21 to 69 years of age at study enrollment. Our analysis was based on follow-up data from 1995 through 2008 in the Black Womens Health Study. Multivariable proportional-hazards models were used to estimate hazard ratios and 95% confidence intervals. RESULTS Of 1773 deaths identified during follow-up, 770 occurred among 33,916 women who had never smoked. Among nonsmokers, the risk of death was lowest for a BMI of 20.0 to 24.9. For a BMI above this range, the risk of death increased as the BMI increased. With a BMI of 22.5 to 24.9 as the reference category, multivariable-adjusted hazard ratios were 1.12 (95% confidence interval [CI], 0.87 to 1.44) for a BMI of 25.0 to 27.4, 1.31 (95% CI, 1.01 to 1.72) for a BMI of 27.5 to 29.9, 1.27 (95% CI, 0.99 to 1.64) for a BMI of 30.0 to 34.9, 1.51 (95% CI, 1.13 to 2.02) for a BMI of 35.0 to 39.9, and 2.19 (95% CI, 1.62 to 2.95) for a BMI of 40.0 to 49.9 (P<0.001 for trend). A large waist circumference was associated with an increased risk of death from any cause among women with a BMI of less than 30.0. CONCLUSIONS The risk of death from any cause among black women increased with an increasing BMI of 25.0 or higher, which is similar to the pattern observed among whites. Waist circumference appeared to be associated with an increased risk of death only among nonobese women. (Funded by the National Cancer Institute.).

Relative validity of food frequency questionnaire nutrient estimates in the Black Women's Health Study.

PURPOSE The Black Womens Health Study (BWHS) was designed to investigate determinants of health and disease in US black women. More than 64,000 women are enrolled in the BWHS cohort. This study assessed the relative validity of the 68-item food frequency questionnaire (FFQ) used in the BWHS baseline questionnaire. METHODS Four hundred and eight BWHS enrollees were asked to provide three telephone, 24-hour recalls and one written 3-day food diary over a one-year period. Means and Pearson correlations were computed to compare estimates for energy, total fat, saturated fat, protein, carbohydrate, dietary fiber, calcium, iron, vitamin C, folate, beta-carotene, and vitamin E from the FFQ, recalls, and diaries. RESULTS Mean energy intake (kcal) was higher for the diary (1716) than the FFQ (1601) or recalls (1510). Other nutrient estimates (% kcal or per 1000 kcal) were similar across methods, except beta-carotene (FFQ higher). Correlations (energy-adjusted, except for energy, and corrected for intraperson variation) between the FFQ and the recalls were higher than for the diary data and were between 0.5 and 0.8, except for energy and vitamin E (both <0.3). CONCLUSION The BWHS FFQ will support meaningful analyses of diet-health associations for 10 of the 11 energy-adjusted nutrient intake variables analyzed.

Onset of Natural Menopause in African American Women

OBJECTIVES This study assessed predictors of the onset of natural menopause in African American women. METHODS We used mailed questionnaires to collect data at baseline in 1995 and during follow-up from Black Womens Health Study participants. Cox proportional hazards regression was used to assess potential predictors-including experiences of racism-of the onset of natural menopause among 17 070 women aged 35 to 55 years and premenopausal in 1995. RESULTS The hazard ratio (HR) was 1.43 for current smokers (95% confidence interval [CI] = 1.24, 1.66) and 1.21 (95% CI = 1.06, 1.38) for ex-smokers and significantly less for obese women and oral contraceptive users. Hazard ratios for most questions about racism were elevated by 10% to 30% but were not statistically significant. CONCLUSIONS Earlier onset of natural menopause among African American women is strongly associated with smoking and inversely associated with body mass index and oral contraceptive use.

Parity and Lactation in Relation to Estrogen Receptor Negative Breast Cancer in African American Women

Background: Estrogen receptor (ER)-negative breast tumors and progesterone receptor (PR)-negative breast tumors occur more commonly in women of African ancestry. Recent research indicates that the effects of reproductive factors may differ by hormone receptor status. We assessed the relation of parity and lactation to incidence of ER−/PR− and ER+/PR+ breast cancer in a cohort of African American women. Methods: From 1995–2009, 457 incident cases of ER+/PR+ and 318 cases of ER−/PR− breast cancer were confirmed by review of pathology data among 59,000 African American women followed in the Black Womens Health Study through biennial questionnaires. HRs and two-sided 95% CIs for the incidence of breast cancer subtypes were derived from proportional hazards regression models that controlled for age, reproductive variables, and breast cancer risk factors. Results: Higher parity was associated with an increased risk of ER−/PR− breast cancer (HR = 1.48, 95% CI: 0.98–1.84 for 3+ versus 0 births, Ptrend = 0.009), and with a reduced risk of ER+/PR+ cancer (HR = 0.53, 95% CI: 0.39–0.73 for 3+ versus 0 births, Ptrend = 0.0002). Among women who had breastfed, high parity was no longer associated with increased incidence of ER−/PR− breast, but the inverse association with ER+/PR+ cancer persisted. Conclusions: The higher incidence of ER−/PR− breast cancer in African American women may be explained in part by their higher parity and lower prevalence of breastfeeding relative to white women. Impact: Increased breastfeeding may lead to a reduction in the incidence of this breast cancer subtype. Cancer Epidemiol Biomarkers Prev; 20(9); 1883–91. ©2011 AACR.

Parity, Lactation, and Breast Cancer Subtypes in African American Women: Results from the AMBER Consortium

BACKGROUND African American (AA) women have a disproportionately high incidence of estrogen receptor-negative (ER-) breast cancer, a subtype with a largely unexplained etiology. Because childbearing patterns also differ by race/ethnicity, with higher parity and a lower prevalence of lactation in AA women, we investigated the relation of parity and lactation to risk of specific breast cancer subtypes. METHODS Questionnaire data from two cohort and two case-control studies of breast cancer in AA women were combined and harmonized. Case patients were classified as ER+ (n = 2446), ER- (n = 1252), or triple negative (ER-, PR-, HER2-; n = 567) based on pathology data; there were 14180 control patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in polytomous logistic regression analysis with adjustment for study, age, reproductive and other risk factors. RESULTS ORs for parity relative to nulliparity was 0.92 (95% CI = 0.81 to 1.03) for ER+, 1.33 (95% CI = 1.11 to 1.59) for ER-, and 1.37 (95% CI = 1.06 to 1.70) for triple-negative breast cancer. Lactation was associated with a reduced risk of ER- (OR = 0.81, 95% CI = 0.69 to 0.95) but not ER+ cancer. ER- cancer risk increased with each additional birth in women who had not breastfed, with an OR of 1.68 (95% CI = 1.15 to 2.44) for 4 or more births relative to one birth with lactation. CONCLUSIONS The findings suggest that parous women who have not breastfed are at increased risk of ER- and triple-negative breast cancer. Promotion of lactation may be an effective tool for reducing occurrence of the subtypes that contribute disproportionately to breast cancer mortality.

Sarcoidosis in Black Women in the United States: Data From the Black Women's Health Study

BACKGROUND Sarcoidosis is a systemic granulomatous disorder of unknown cause that occurs among men and women of all races. In the United States, black women are most frequently and most severely affected. There have been few epidemiologic studies of sarcoidosis focusing on black women. METHODS In this article, we present data on incidence, prevalence, and clinical characteristics of sarcoidosis among participants in the Black Womens Health Study, a cohort study of 59,000 black women from across the United States. Data on incident disease and potential risk factors are obtained through biennial questionnaires. Follow-up has been > 80% through six completed cycles. RESULTS There were 685 prevalent cases of sarcoidosis at baseline in 1995 and 435 incident cases reported during 611,585 person-years of follow-up through 2007, for an average annual incidence rate of 71/100,000 and a current prevalence of 2.0%. The sarcoid diagnosis was confirmed in 96% of self-reported cases for whom medical records or physician checklists were obtained. The most frequently affected site was the lung. Most patients also had extrapulmonary involvement, with the most common sites being lymph nodes, skin, and eyes. Prednisone had the highest prevalence of use, followed by inhaled corticosteroids. CONCLUSIONS This study confirms previous reports of high incidence and prevalence of sarcoidosis among black women, as well as the extent of extrapulmonary disease, frequent need for steroid therapy, and comorbid conditions in this population. The prospective identification of sarcoidosis cases from a defined population will enable a valid assessment of risk factors for incident disease as follow-up continues.

Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies

BACKGROUND Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. OBJECTIVE We investigated these associations in a pooled analysis of 18 cohort studies. DESIGN Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. RESULTS α-Carotene, β-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): α-carotene (0.87; 95% CI: 0.78, 0.97), β-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): α-carotene (1.04; 95% CI: 0.99, 1.09), β-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for β-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend ≤ 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. CONCLUSIONS Intakes of α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources.

Fine-Mapping of Breast Cancer Susceptibility Loci Characterizes Genetic Risk in African Americans

Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and replicated associations (P < 0.05) with only 4 variants. Through fine-mapping, we identified markers in four regions that better capture the association with breast cancer risk in African Americans as defined by the index signal (2q35, 5q11, 10q26 and 19p13). We also identified statistically significant associations with markers in four separate regions (8q24, 10q22, 11q13 and 16q12) that are independent of the index signals and may represent putative novel risk variants. In aggregate, the more informative markers found in the study enhance the association of these risk regions with breast cancer in African Americans [per allele odds ratio (OR) = 1.18, P = 2.8 × 10(-24) versus OR = 1.04, P = 6.1 × 10(-5)]. In this detailed analysis of the known breast cancer risk loci, we have validated and improved upon markers of risk that better characterize their association with breast cancer in women of African ancestry.

Child and Adolescent Abuse in Relation to Obesity in Adulthood: The Black Women’s Health Study

OBJECTIVE: To investigate the association of physical and sexual abuse in childhood and adolescence with risk of adult obesity among black women in the United States. METHODS: Participants were women enrolled in the Black Women’s Health Study, an ongoing prospective cohort study begun in 1995. In 2005, 33 298 participants completed a self-administered questionnaire on early life experiences of abuse. Log-binomial regression models were used to derive risk ratios (RRs) and 95% confidence intervals (CIs) for the relation of child/teenager abuse with obesity (BMI ≥30) and central adiposity (waist circumference >35 inches) reported in 2005. RESULTS: The RR for BMI ≥30, a measure of overall obesity, was 1.29 (95% CI 1.20–1.38) for the highest severity of exposure to child/teenager physical and sexual abuse relative to no abuse. After controlling for postulated intermediates, including reproductive history, diet, physical activity, depressive symptoms, and socioeconomic status, the RR was 1.14 (95% CI 1.08–1.21). The RR for waist circumference >35 inches, which measures central obesity, for severe physical and sexual abuse relative to no abuse was 1.29 (95% CI 1.19–1.38) before adjustment for intermediates and 1.18 (95% CI 1.10–1.27) after adjustment. CONCLUSIONS: Early life sexual and physical abuse was associated with an increased risk of overall and central obesity in adulthood. Although the association between abuse and obesity was explained to some extent by health behaviors, reproductive history, and mental health, these factors did not fully account for the associations. Our data suggest that early life adversity is related to adult body size and weight distribution.

Postpartum remodeling, lactation, and breast cancer risk: summary of a National Cancer Institute-sponsored workshop.

The pregnancy-lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes.