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1.  Impact of Obesity on Cancer Survivorship and the Potential Relevance of Race and Ethnicity 
Evidence that obesity is associated with cancer incidence and mortality is compelling. By contrast, the role of obesity in cancer survival is less well understood. There is inconsistent support for the role of obesity in breast cancer survival, and evidence for other tumor sites is scant. The variability in findings may be due in part to comorbidities associated with obesity itself rather than with cancer, but it is also possible that obesity creates a physiological setting that meaningfully alters cancer treatment efficacy. In addition, the effects of obesity at diagnosis may be distinct from the effects of weight change after diagnosis. Obesity and related comorbid conditions may also increase risk for common adverse treatment effects, including breast cancer–related lymphedema, fatigue, poor health–related quality of life, and worse functional health. Racial and ethnic groups with worse cancer survival outcomes are also the groups for whom obesity and related comorbidities are more prevalent, but findings from the few studies that have addressed these complexities are inconsistent. We outline a broad theoretical framework for future research to clarify the specifics of the biological–social–environmental feedback loop for the combined and independent contributions of race, comorbid conditions, and obesity on cancer survival and adverse treatment effects. If upstream issues related to comorbidities, race, and ethnicity partly explain the purported link between obesity and cancer survival outcomes, these factors should be among those on which interventions are focused to reduce the burden of cancer.
PMCID: PMC3776266  PMID: 23990667
2.  Racial variation in vitamin D cord blood concentration in White and Black male neonates 
Cancer causes & control : CCC  2012;24(1):91-98.
To evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates.
In 2004/2005 venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, US. 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured by radioimmunoassay (RIA), testosterone, estradiol and sex hormone binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed.
Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95% CI 10.10–12.95 ng/mL vs. 18.24; 95% CI 15.32–21.72 ng/mL; p<0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D < 20 ng/mL] than whites (84% vs. 63%). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother’s parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)2D did not differ by race. 25(OH)D and 1,25(OH)2D did not correlate with IGFs, sex steroid hormones and SHBG.
Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother’s parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthood.
PMCID: PMC3529856  PMID: 23139102
Vitamin D; umbilical cord blood; black and white Americans
3.  Dopamine Polymorphisms and Depressive Symptoms Predict Foods Intake: Results from a Nationally Representative Sample 
Appetite  2011;57(2):339-348.
Depression and variation in dopamine related genes have both independently been associated with food consumption. Depressive symptoms could synergistically interact with genetic variation to influence food intake. We examined the interaction between high depressive symptoms and functional polymorphisms of dopamine transportor (SLC6A3), monoamine oxidase A (MAOA), dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) on intake of high-calorie sweet, high-calorie non-sweet, and low-calorie foods in the National Longitudinal Study of Adolescent Health (Add Health). Multivariate linear regression analyses were used to examine main effects of gene and depression symptoms and their interaction (genotype-by-high depression symptoms) on food categories. Applying a false discovery rate criterion for multiple comparisons indicated a statistically significant interaction for females with high depressive symptoms and the SLC6A3 gene, such that those with the SLC6A3 10/10 allele reported greater intake of high-calorie sweet foods than their counterparts high in depressive symptoms with the SLC6A3 any 9 allele (LS mean 10/10 allele = 2.5, SE = .13; LS mean any 9 allele = 1.8, SE = .13, p<.05). These findings highlight that the relationship between depression and food intake may vary as a function of genetic polymorphism. Further research is needed to confirm these findings.
PMCID: PMC3156384  PMID: 21672565
Adolescent; Diet; Dopamine; Depression
4.  Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model—Recommendations From an NIH Workshop 
Genetic epidemiology  2011;10.1002/gepi.20571.
Although it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene-environment interaction remain a challenge and have had limited success to date. Given the current state-of-the-science, NIH sought input on ways to accelerate investigations of gene-environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene-environment interaction studies. Participants of the NIH Gene-Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene-environment interactions. Further, participants also emphasized the continued need for high-quality measures of environmental exposures and new genomic technologies in ongoing and new studies.
PMCID: PMC3228883  PMID: 21308768
gene-environment interaction; epidemiology; study design; genetics; environment
5.  Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates 
Cancer causes & control : CCC  2012;23(3):445-454.
To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF)-axis between female African-American and white neonates.
Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate (DHEAS), estradiol, sex-steroid hormone binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones.
African-American neonates weighed less at birth (3,228 vs. 3,424 grams, p<0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3 and the molar ratio of IGF1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 vs. 1.47 ng/mL, p=0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p=0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 vs. 539.2 ng/mL, p=0.04).
We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations.
PMCID: PMC3333795  PMID: 22252677
umbilical cord blood; IGF axis; sex steroid hormones; African American
6.  Dietary patterns and the risk of colorectal adenomas: the Black Women's Health Study 
Colorectal adenomas are benign lesions that may be precursors to colorectal cancer. No studies of African American women have investigated dietary patterns and the risk of colorectal adenomas. We examined data from the Black Women's Health Study (BWHS) to determine whether dietary patterns are associated with the risk of colorectal adenomas.
This is a prospective cohort study of 59,000 participants followed biennially since 1995. During 155,414 person-years of follow-up from 1997 to 2007 among women who had had at least one screening colonoscopy, 620 incident cases of colorectal adenomas were identified. Using Cox regression models, we obtained incident rate ratios (IRR) for colorectal adenoma in relation to quintiles of each of two dietary patterns, adjusting for other colorectal adenoma risk factors.
Two dietary patterns, Western and prudent, were utilized to assess the association between dietary intake and adenoma risk. The highest quintile of prudent diet, relative to the lowest quintile, was significantly associated with 34% lower colorectal adenoma risk overall (incidence rate ratio, IRR=0.66; 95% CI, 0.50-0.88; p for trend, < 0.01). Higher scores on the Western pattern were associated with higher risk of colorectal adenoma (IRR = 1.42, 95% CI 1.09-1.85 for the highest quintile relative to the lowest; p trend, 0.01).
Our findings suggest that African American women may be able to reduce their risk of developing colorectal adenomas by following a prudent dietary pattern and avoiding a more Western pattern.
Impact Statement
A dietary modification could have a strong impact in colorectal adenoma prevention in African American women.
PMCID: PMC3089689  PMID: 21357379
7.  Racial variation in umbilical cord blood leptin concentration in male babies 
We hypothesize that racial differences in utero contribute to the racial disparity in prostate cancer risk. Leptin is a candidate for evaluating this hypothesis because it influences fetal development and newborn growth.
We measured leptin concentration by ELISA in venous cord blood collected from 70 African-American and 37 white male full-term births. We measured sex steroid hormones and insulin-like growth factor (IGF) axis concentrations previously. Separately by race, we calculated the geometric mean leptin concentration and estimated the geometric mean adjusted for birth and placental weights, mother’s age and parity, time of day and season of birth, and sex steroid hormone and IGF-axis concentrations using linear regression.
Leptin was positively correlated with birth (r=0.34) and placental (r=0.25) weights, IGF-1 (r=0.21), and IGF binding protein-3 (r=0.29) adjusting for race. Unadjusted geometric mean leptin did not differ (p=0.92) between African Americans (5,280 pg/mL; 95% CI: 4,322-6,451) and whites (5,187 pg/mL; 95% CI: 3,938-6,832). Adjusted geometric mean leptin was nonstatistically significantly higher (p=0.15) in African Americans (5,954 pg/mL; 95% CI: 4,725-7,502) than whites (4,133 pg/mL; 95% CI: 2,890-5,910).
We observed a non-significantly higher adjusted cord blood leptin concentration in African-American compared with white male babies, although unadjusted levels were similar.
These findings do not support the hypothesis that leptin level in utero contributes to the racial disparity in prostate cancer risk in adulthood.
PMCID: PMC3070060  PMID: 21307303
Leptin; in utero; race; male
8.  Association Between Self-Reported Household Practices and Body Mass Index of US Children and Adolescents, 2005 
Parents can set household practices that influence children’s behaviors. The objective of this study was to determine whether children (children and adolescents aged 9–18 y) who live in a household that has healthful practices related to behaviors associated with obesity have a lower body mass index (BMI).
We analyzed data from the 2005 Styles mail panel survey (N = 1,685 parents and children). We used multiple logistic regression to assess associations between 4 household practices and 3 children’s behaviors: watching television, participating in vigorous physical activity, and purchasing sodas and snacks at school.
Children watched more television if they had a television in their bedrooms, were less active as a family, and had no junk food restrictions at home. Children in less active families participated in about half as much VPA as children in more active families. Children purchased more sodas and snacks at school if they had a television in their bedrooms and their family consumed more meals at fast-food restaurants. Children whose families were less active were more likely to have a self-reported BMI at or above the 85th percentile. In addition, children who watched more television were more likely to have a self-reported BMI at or above the 85th percentile.
Household practices were associated with children’s behaviors and self-reported BMI. A household profile that includes being active as a family may counteract the increase in childhood obesity.
PMCID: PMC3523893  PMID: 23237244
9.  Racial variation in sex steroid hormones and the insulin-like growth factor axis in umbilical cord blood of male neonates 
To address whether umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF)-axis differ between African-American and white male neonates.
In 2004/2005, venous cord blood samples were collected from 75 African-American and 38 white male full-term uncomplicated births along with birth weight, placental weight, mother’s age and parity, and time of birth. Testosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) were measured by immunoassay, and IGF-1, IGF-2, and IGF binding protein (BP)-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed.
Androstanediol glucuronide, estradiol, and SHBG concentrations did not differ by race; however, the molar ratio of testosterone to SHBG was higher in African-American than white male babies after adjustment (p=0.01). Both before and after adjustment, whites had higher concentrations of IGF-1 (adjusted; white, African-American: 93.1, 71.9 ng/mL), IGF-2 (537.3, 474.8 ng/mL), and IGFBP-3 (1673, 1482 ng/mL) than African-Americans (p<0.05), although the molar ratio of IGF-1 plus IGF-2 to IGFBP-3 did not differ by race.
The higher cord blood testosterone to SHBG ratio in African-American compared with white male babies after taking into account maternal and birth factors is compatible with the hypothesis that differences in androgen levels in utero contribute to their higher prostate cancer risk, although we would have expected crude differences as well. Lower cord blood IGF-1 and IGF-2 levels in African-American compared with white male babies are not consistent with the hypothesis that differences in growth factor levels contribute to their higher prostate cancer risk.
PMCID: PMC3012385  PMID: 19423525
10.  Genes implicated in serotonergic and dopaminergic functioning predict BMI categories 
Obesity (Silver Spring, Md.)  2008;16(2):348-355.
This study addressed the hypothesis that variation in genes associated with dopamine function (SLC6A3, DRD2, DRD4), serotonin function (SLC6A4), and regulation of monoamine levels (MAOA) may be predictive of BMI categories (obese and overweight + obese) in young adulthood and of changes in BMI as adolescents transition into young adulthood. Interactions with gender and race/ethnicity were also examined.
Research Methods and Procedures
Participants were a subsample of individuals from The National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset of 1584 unrelated individuals with genotype data. Multiple logistic regressions were conducted to evaluate associations between genotypes and obesity (BMI > 29.9) or overweight + obese combined (BMI > 25) with normal weight (BMI = 18.5–24.9) as a referent. Linear regression models were used examine change in BMI from adolescence to young adulthood.
Significant associations were found between SLC6A4 5HTTLPR and categories of BMI, and between MAOA promoter VNTR among males and categories of BMI. Stratified analyses revealed that the association between these two genes and excess BMI was significant for males overall, and for White and Hispanic males specifically. Linear regression models indicated a significant effect of SLC6A4 5HTTLPR on change in BMI from adolescence to young adulthood.
Our findings lend further support to the involvement of genes implicated in dopamine and serotonin regulation on energy balance.
PMCID: PMC2919156  PMID: 18239643
Adolescents; Genetic Epidemiology; Serotonin; Neuro Transmitter
11.  Interactions between genotype and depressive symptoms on obesity 
Behavior genetics  2009;39(3):296-305.
Depression and Genetic variation in serotonin and monoamine transmission have both been associated with Body Mass Index (BMI), but their interaction effects are not well understood. We examined the interaction between depressive symptoms and functional polymorphisms of serotonin transporter (SLC6A4) and monoamine oxidase A (MAOA) on categories of BMI.
Participants were from the National Longitudinal Study of Adolescent Health. Multiple logistic regression was used to investigate interactions between candidate genes and depression on risk of obesity (BMI≥30) or overweight + obese combined (BMI≥25).
Males with an MAOA active allele with high depressive symptoms were at decreased risk of obesity (OR, 0.22; 95% CI, 0.06 – 0.78) and overweight + obesity (OR, 0.48; 95% CI, 0.26 – 0.89). No similar effect was observed among females.
These findings highlight that the obesity-depression relationship may vary as a function of gender and genetic polymorphism, and suggest the need for further study.
PMCID: PMC2884968  PMID: 19337825
12.  Public Health Genomics: Translating Obesity Genomics Research Into Population Health Benefits 
Obesity (Silver Spring, Md.)  2008;16(Suppl 3):S85-S94.
We examine how a public health genomics framework can be used to move genomic discoveries into clinical and public health practice for obesity prevention and treatment. There are four phases of translational research: T1: discovery to candidate health application; T2: health application to evidence-based practice guidelines; T3: practice guidelines to health practice; and T4: practice to population health impact. Types of multidisciplinary research and knowledge synthesis needed for each phase, as well as the importance of developing and disseminating evidence-based guidelines, are discussed. Because obesity genomics research is mostly in the discovery phase or in the very early phases of translation (T1), the authors present this framework to illustrate the range of translation activities needed to move genomic discoveries in obesity to actual applications that reduce the burden of obesity at the population level.
PMCID: PMC2736102  PMID: 19037221
13.  Studying Gene–Behavior Interactions: Summary of Recommendations 
Obesity (Silver Spring, Md.)  2008;16(Suppl 3):S95-S96.
PMCID: PMC2719886  PMID: 19037222
15.  Will web-based research suffice when collecting U.S. school district policies? The case of physical education and school-based nutrition policies 
Recognizing the growing childhood overweight problem, a number of school-based strategies, including policy approaches, have been proposed and are being implemented to address the problem considering the amount of time children spend in schools. This paper describes the results of a pilot study that tested approaches to collecting U.S. school district policy information regarding physical education and nutrition requirements that can inform efforts by policy makers, researchers, advocates and others interested in collecting school district-level obesity-related policies that are typically not systematically available from a "one stop" source.
Sixty local school districts representing six states were selected for conducting the district policy research, with larger, urban school districts over-sampled to facilitate collection of policies from districts representing a larger proportion of the public school population in each study state. The six states within which the pilot districts were located were chosen based on the variability in their physical education and school-based nutrition policy and geographic and demographic diversity. Web research and a mail canvass of the study districts was conducted between January and May 2006 to obtain all relevant policies. An additional field collection effort was conducted in a sample of districts located in three study states to test the extent to which field collection would yield additional information.
Policies were obtained from 40 (67%) of the 60 districts, with policies retrieved via both Web and mail canvass methods in 16 (27%) of the districts, and were confirmed to not exist in 10 (17%) of the districts. Policies were more likely to be retrieved from larger, urban districts, whereas the smallest districts had no policies available on the Web. In no instances were exactly the same policies retrieved from the two sources. Physical education policies were slightly more prevalent than nutrition policies.
Collection of U.S. local school district policies requires a multi-pronged approach. Web research and mail canvasses will likely yield different types of policy information. Given the variance in district-level Web site presence, researchers and others interested in obtaining district physical education and nutrition-related policies should consider supplementing Web research with more direct methods.
PMCID: PMC2637297  PMID: 19077186

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