Shaneda Warren Andersen

Prospective cohort study of general and central obesity, weight change trajectory and risk of major cancers among Chinese women

General obesity, typically measured using body mass index (BMI), has been associated with an increased risk of several cancers. However, few prospective studies have been conducted in Asian populations. Although central obesity, often measured using waist–hip ratio (WHR), is more predictive for type 2 diabetes and cardiovascular diseases (CVD) risk than BMI, knowledge of its association with cancer incidence is limited. In a cohort of 68,253 eligible Chinese women, we prospectively investigated the association of BMI, WHR and weight change during adulthood with risk of overall cancer and major site‐specific cancers using multivariate Cox proportional hazard models. Compared to the BMI group of 18.5–22.9 kg/m2, obese (BMI ≥ 30 kg/m2) women were at an increased risk of developing overall cancer (hazard ratio = 1.36, 95% confidence interval = 1.21–1.52), postmenopausal breast cancer (HR: 2.43, 95% CI: 1.73–3.40), endometrial cancer (HR: 5.34, 95% CI: 3.48–8.18), liver cancer (HR: 1.93, 95% CI: 1.14–3.27) and epithelial ovarian cancer (HR: 2.44, 95% CI: 1.37–4.35). Weight gain during adulthood (per 5 kg gain) was associated with increased risk of all cancers combined (HR: 1.05, 95% CI: 1.03–1.08), postmenopausal breast cancer (HR: 1.17, 95% CI: 1.10–1.24) and endometrial cancer (HR: 1.37, 95% CI: 1.27–1.48). On the other hand, WHR was not associated with cancer risk after adjustment for baseline BMI. These findings suggest that obesity may be associated with cancer risk through different mechanisms from those for type 2 diabetes and CVD and support measures of maintaining health body weight to reduce cancer risk in Chinese women.

Adherence to Cancer Prevention Guidelines and Cancer Risk in Low-Income and African American Populations

Background: The American Cancer Society (ACS) publishes behavioral guidelines for cancer prevention, including standards on body weight, physical activity, nutrition, alcohol, and tobacco use. The impact of these guidelines has been rarely studied in low-income and African American populations. Methods: The study included 61,098 racially diverse, mainly low-income adults who participated in the Southern Community Cohort Study and were followed for a median of 6 years. Cox models were used to estimate HRs for cancer incidence associated with behaviors and with an ACS physical activity/nutrition 0-to-4 compliance score indicating the number of body weight, physical activity, healthy eating, and alcohol guidelines met. Results: During the study period, 2,240 incident cancers were identified. Significantly lower cancer incidence was found among never smokers and non/moderate alcohol drinkers, but not among those meeting guidelines for obesity, physical activity, and diet. The ACS compliance score was inversely associated with cancer risk among the 25,509 participants without baseline chronic disease. HRs for cancer incidence among those without baseline chronic diseases and who met one, two, three, or four guidelines versus zero guidelines were 0.93 (95% confidence intervals, 0.71–1.21), 0.85 (0.65–1.12), 0.70 (0.51–0.97), and 0.55 (0.31–0.99), respectively. Associations were consistent in analyses stratified by sex, race, household income, and smoking status. Conclusions: Meeting the ACS smoking and body weight/physical activity/dietary/alcohol guidelines for cancer prevention is associated with reductions in cancer incidence in low-income and African American populations. Impact: This study provides strong evidence supporting lifestyle modification to lower cancer incidence in these underserved populations. Cancer Epidemiol Biomarkers Prev; 25(5); 846–53. ©2016 AACR.

Associations Between Neighborhood Environment, Health Behaviors, and Mortality

INTRODUCTION Considering the joint association of neighborhood socioeconomic environment and individual-level health behaviors with health outcomes may help officials design effective disease prevention strategies. This study evaluates the joint influences of neighborhood socioeconomic environment and individual health behaviors on mortality in a cohort primarily comprising people with low individual-level SES. METHODS The prospective Southern Community Cohort Study includes 77,896 white and African American participants recruited in the years 2002-2009; 55% of participants had a household income <

Combined Impact of Health Behaviors on Mortality in Low-Income Americans

15,000 at baseline interview. Mortality from cancer (n=2,471), cardiovascular diseases (n=3,005), and all-causes (n=10,099) was identified from the National Death Index through December 31, 2013 (median follow-up, 8 years). Data were analyzed in 2016 and 2017. Associations were assessed between mortality, a neighborhood deprivation index composed of 11 census tract-level variables, five health behaviors, and a composite healthy lifestyle score. RESULTS Living in a neighborhood with the greatest socioeconomic disadvantage was associated with higher all-cause mortality in both men (hazard ratio=1.41, 95% CI=1.27, 1.57) and women (hazard ratio=1.77, 95% CI=1.57, 2.00). Associations were attenuated after adjustment for individual-level SES and major risk factors (hazard ratio for men=1.09, 95% CI=0.98, 1.22, and hazard ratio for women=1.26, 95% CI=1.12, 1.42). The dose-response association between neighborhood disadvantage and mortality was less apparent among smokers. Nevertheless, individuals who lived in disadvantaged neighborhoods and had the unhealthiest lifestyle scores experienced the highest mortality. CONCLUSIONS Disadvantaged neighborhood socioeconomic environments are associated with increased mortality in a cohort of individuals of low SES. Positive individual-level health behaviors may help negate the adverse effect of disadvantage on mortality.

Prospective Cohort Study of Central Adiposity and Risk of Death in Middle Aged and Elderly Chinese

INTRODUCTION African Americans and low-income whites have higher mortality than the U.S. general population. This study prospectively investigated the combined influence of major lifestyle factors and poverty on mortality in this vulnerable population. METHODS Data were collected in 2002-2009 from 79,101 Southern Community Cohort Study participants, of which 67% were African American and 55% had household incomes <

Total and free circulating vitamin D and vitamin D binding protein in relation to colorectal cancer risk in a prospective study of African Americans

15,000. Mortality outcomes were identified from the National Death Index though December 31, 2011 (data analyzed in 2014-2015). Healthy behavior scores were created based on tobacco smoking, alcohol intake, diet, physical activity, and sedentary time. The primary analysis was performed based on the score created by counting each participant as having met/not met public health guidelines for each behavior. RESULTS Healthy behavior scores were associated with reduced cancer, cardiovascular disease, and all-cause mortality. Associations were stronger for whites than African Americans: hazard ratios for all-cause mortality comparing participants meeting four or five guidelines versus participants meeting zero were 0.41 (95% CI=0.30, 0.55) for African American men; 0.36 (95% CI=0.24, 0.55) for white men; 0.46 (95% CI=0.36, 0.59) for African American women; and 0.27 (95% CI=0.18, 0.43) for white women. The association between healthy lifestyle and all-cause mortality was weaker among those with incomes <

Identifying Biomarkers for Risk of Premature Menopause Among Childhood Cancer Survivors May Lead to Targeted Interventions and Wellness Strategies

15,000 than those with higher income, particularly in men (p<0.05 for interaction). CONCLUSIONS This study demonstrates the importance of health behaviors on mortality among all groups, but highlights the need for additional research to identify factors contributing to high risk of mortality among low-income and African American populations.

Abstract 3272: Association between estrogen-metabolizing genetic risk scores and breast cancer risk

Asians have high prevalence of central obesity despite the low prevalence of general obesity. We evaluated associations between the central obesity measure, waist-hip ratio (WHR) with total and cause-specific mortality in middle-aged and elderly Chinese participants. Data arise from two prospective population-based cohort studies: the Shanghai Men’s Health Study involves 53,425 men (participation rate = 74.0%), age 40–74 at baseline, and the Shanghai Women’s Health Study involves 63,017 women (participation rate = 92.7%), age 40–70 at baseline. Information on lifestyle factors and anthropometric measurements were taken at baseline interview. Vital status and causes of death were obtained via surveys and annual linkages to relevant Shanghai registries through December 31, 2011. After median follow-up time of 7.5 years for the Shanghai Men’s Health Study and 13.2 years for the Shanghai Women’s Health Study, there were 2,058 and 3,167 deaths, respectively. In models adjusted for BMI and other potential confounders, WHR was associated with all-cause mortality; hazard ratios (HRs) (95% confidence intervals) across the first to fifth quintile increased from 1 (Reference), 1.10 (0.95,1.27), 1.21 (1.04,1.41), 1.11 (0.96,1.30), to 1.42 (1.22,1.65) in men and from 1 (Reference), 1.10 (0.96,1.27), 1.11 (0.97,1.27), 1.20 (1.05,1.37), to 1.48 (1.30,1.69) in women. WHR had a stronger association with cardiovascular disease, with multivariate-adjusted HRs of 1.5 to 1.7 observed for the highest versus lowest quintile of WHR. Dose-response associations were also seen for cancer and other-cause deaths. Stratified analyses suggested a stronger association with mortality among normal weight (BMI <25) than over-weight (BMI ≥25) individuals. Positive associations with mortality were observed in subgroups defined by follow-up duration, comorbidity, age, smoking, and physical activity. Greater central adiposity is associated with increased mortality in Chinese adults, even among individuals with low BMI. Physicians and the public should be aware of central adiposity’s independent effects on health.

Abstract B34: Total and free vitamin D, vitamin D binding protein, and colorectal cancer risk in the Southern Community Cohort Study

Background: Previous studies rarely evaluated the associations between vitamin D–binding protein and free vitamin D with colorectal cancer risk. We assessed these biomarkers and total 25-hydroxyvitamin D in relation to colorectal cancer risk in a sample of African Americans. Methods: Cases comprised 224 African American participants of the Southern Community Cohort Study diagnosed with incident colorectal cancer. Controls (N = 440) were selected through incidence density sampling and matched to cases on age, sex, and race. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between biomarker levels and colorectal cancer risk. Results: Vitamin D was inversely associated with colorectal cancer risk where the OR per-SD increase in total and free 25-hydroxyvitamin D were 0.82 (95% CI, 0.66–1.02) and 0.82 (95% CI, 0.66–1.01), respectively. Associations were most apparent among cases diagnosed >3 years after blood draw: ORs for the highest tertile versus the lowest were 0.69 (95% CI, 0.21–0.93) for total 25-hydroxyvitamin D and 0.71 (95% CI, 0.53–0.97) for free 25-hydroxyvitamin D. Inverse associations were seen in strata defined by sex, BMI, and anatomic site, although not all findings were statistically significant. Vitamin D–binding protein was not associated with colorectal cancer risk. Conclusions: Our findings suggest that total and free 25-hydroxyvitamin D may be inversely associated with colorectal cancer risk among African Americans. Impact: These findings highlight a potential role for vitamin D in colorectal cancer prevention in African Americans. Cancer Epidemiol Biomarkers Prev; 26(8); 1242–7. ©2017 AACR.

Abstract 861: The association between cancer prevention guidelines and cancer risk in the Southern Community Cohort Study

Female survivors of childhood cancer are at risk of late effects of their cancer treatment including increased risk of premature menopause before age 40 years (1). Premature menopause causes infertility at an early age, and also is linked to other adverse health outcomes such as heart disease and osteoporosis (2). Identifying biomarkers that define risk strata for treatmentassociated premature menopause may allow survivors to partake in targeted medical interventions aimed to reduce or prevent the consequences of premature menopause, such as fertility preservation procedures and prevention programs for cardiovascular diseases and osteoporosis. In this issue of the Journal, Brooke and colleagues aim to identify these potential biomarkers in a report describing the first systematic assessment of the how genetic factors may influence risk of premature menopause among childhood cancer survivors (3). The study uses data from 799 female participants in the St. Jude Lifetime Cohort Study (4) to conduct a genomewide association study of the prevalence of clinically diagnosed premature menopause at study entry. The authors provide evidence that a high-risk haplotype upstream from Neuropeptide Y Receptor Y2 (NPY2R) associates with prevalence of premature menopause, where strongest associations are observed among participants exposed to ovarian radiotherapy. Although attenuated, the association between homozygosity for the haplotype and increased prevalence of premature menopause among survivors exposed to ovarian radiotherapy replicates in analyses using data from 1624 survivors enrolled in the Childhood Cancer Survivor Study. Additional evidence of the genetic association with premature menopause is provided through bioinformatics analyses. The authors examine genotype tissue expression (GTEx) data and find that NPY2R is most highly expressed in hypothalamus tissue, the portion of the brain that controls the release of pituitary hormones. Importantly, NPY2R regulates the gene NPY that other investigators have shown is involved in the luteinizing hormone surge before ovulation in mice (5,6). The results of the study by Brooke et al. (3) support incorporating genetic data into prediction models of treatmentassociated premature menopause. However, the study has several limitations that should be addressed in future validation studies before clinical implementation into prediction models. Specifically, the control participants are on average younger than the case patients, where a large majority of the control participants are younger than age 40 years and are still at risk of developing premature menopause. To address this limitation, the authors conducted an analysis that adjusts for age at clinical assessment for premature menopause and found similar results. Future causal inferences of the association between the high-risk haplotype ’and treatmentassociated premature menopause will be strengthened if the association persists as more participants develop premature menopause. Additionally, the study lacks data on the timing of premature menopause in participants. Information on how genetic variation may influence age at premature menopause would be useful for childhood cancer survivors when making fertility decisions. It is important to mention that the majority of participants are of European ancestry, potentially limiting the generalizability of the study results to other racial groups. Lastly, the study’s small sample size suggests that there may be additional variants to be identified in association with premature menopause induced by childhood cancer treatment. Identifying women at higher risk of premature menopause is valuable for a variety of reasons. Female childhood cancer survivors have more concerns about future fertility than young adults who have not been diagnosed with cancer (7). A biomarker for risk of premature menopause may help to assuage