Neomi Vin-Raviv

DNA methylation in white blood cells: association with risk factors in epidemiologic studies.

Alterations in DNA methylation patterns, both at specific loci and overall in the genome, have been associated with many different health outcomes. In cancer and other diseases, most of these changes have been observed at the tissue level. Data on whether DNA methylation changes in white blood cells (WBC) can serve as a useful biomarker for different health outcomes are much more limited, but rapidly emerging. Epidemiologic studies have reported associations between global WBC methylation and several different cancers including cancers of the colon, bladder, stomach, breast and head and neck, as well as schizophrenia and myelodysplastic syndrome. Evidence for WBC methylation at specific loci and disease risk is more limited, but increasing. Differences in WBC DNA methylation by selected risk factors including demographic (age, gender, race), environmental exposures (benzene, persistent organic pollutants, lead, arsenic, and air pollution), and other risk factors (cigarette smoke, alcohol drinking, body size, physical activity and diet) have been observed in epidemiologic studies though the patterns are far from consistent. Challenges in inferences from the existing data are primarily due to the cross-sectional and small size of most studies to date as well as the differences in results across assay type and source of DNA. Large, prospective studies will be needed to understand whether changes in risk factors are associated with changes in DNA methylation patterns, and if changes in DNA methylation patterns are associated with changes in disease endpoints.

Racial Disparities in Posttraumatic Stress After Diagnosis of Localized Breast Cancer: The BQUAL Study

BACKGROUND Little is known about the development of posttraumatic stress disorder (PTSD) over time among women diagnosed with breast cancer. This study examines changes in PTSD symptoms in the first 6 months after diagnosis and assesses racial/ethnic differences in PTSD symptomatology over time. METHODS We recruited women with newly diagnosed breast cancer, stages I to III, from three sites in the United States. Three telephone interviews were conducted: baseline at about 2 to 3 months after diagnosis, first follow-up at 4 months after diagnosis, and second follow-up at 6 months after diagnosis. We measured traumatic stress in each interview using the Impact of Events Scale; recorded sociodemographic, tumor, and treatment factors; and used generalized estimating equations and polytomous logistic regression modeling to examine the associations between variables of interest and PTSD. RESULTS Of 1139 participants, 23% reported symptoms consistent with a diagnosis of PTSD at baseline, 16.5% at first follow-up, and 12.6% at the second follow-up. Persistent PTSD was observed among 12.1% participants, as defined by having PTSD at two consecutive interviews. Among participants without PTSD at baseline, 6.6% developed PTSD at the first follow-up interview. Younger age at diagnosis, being black (odds ratio [OR] = 1.48 vs white, 95% confidence interval [CI] =1.04 to 2.10), and being Asian (OR = 1.69 vs white, 95% CI = 1.10 to 2.59) were associated with PTSD. CONCLUSIONS Nearly one-quarter of women newly diagnosed with breast cancer reported symptoms consistent with PTSD shortly after diagnosis, with increased risk among black and Asian women. Early identification of PTSD may present an opportunity to provide interventions to manage symptoms.

Race/ethnicity and socio-economic differences in breast cancer surgery outcomes

BACKGROUND The purpose of this study is to evaluate racial and socio-economic differences in breast cancer surgery treatment, post-surgical complications, hospital length of stay and mortality among hospitalized breast cancer patients. METHODS We examined the association between race/ethnicity and socio-economic status with treatment and outcomes after surgery among 71,156 women hospitalized with a primary diagnosis of breast cancer using the Nationwide Inpatient Sample database from 2007 to 2011. Multivariable regression models were used to compute estimates, odds ratios and 95% confidence intervals adjusting for age, comorbidities, stage at diagnosis, insurance, and residential region. RESULTS Black women were more likely to receive breast conserving surgery but less likely to receive mastectomies compared with white women. They also experienced significantly longer hospital stays (β=0.31, 95% CI: 0.24, 0.39), post-surgical complications (OR=1.21, 95% CI: 1.04-1.42) and in-hospital mortality (OR=1.26, 95% CI: 1.07-1.50) compared with Whites, after adjusting for other factors including the number of comorbidities and treatment type. CONCLUSION Among patients hospitalized for breast cancer, there were racial differences observed in treatment and outcomes. Further studies are needed to fully characterize whether these differences are due to individual, provider level or hospital level factors, and to highlight areas for targeted approaches to eliminate these disparities.

Depression and Anxiety Disorders among Hospitalized Women with Breast Cancer.

Purpose To document the prevalence of depression and anxiety disorders, and their associations with mortality among hospitalized breast cancer patients. Methods We examined the associations between breast cancer diagnosis and the diagnoses of anxiety or depression among 4,164 hospitalized breast cancer cases matched with 4,164 non-breast cancer controls using 2006-2009 inpatient data obtained from the Nationwide Inpatient Sample database. Conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) for the associations between breast cancer diagnosis and diagnoses of anxiety or depression. We also used binary logistic regression models to examine the association between diagnoses of depression or anxiety, and in-hospital mortality among breast cancer patients. Results We observed that breast cancer cases were less likely to have a diagnosis of depression (OR=0.63, 95% CI: 0.52-0.77), and less likely to have a diagnosis of anxiety (OR=0.68, 95% CI: 0.52-0.90) compared with controls. This association remained after controlling for race/ethnicity, residential income, insurance and residential region. Breast cancer patients with a depression diagnosis also had lower mortality (OR=0.69, 95% CI: 0.52-0.89) compared with those without a depression diagnosis, but there was no significant difference in mortality among those with and without anxiety diagnoses. Conclusion Diagnoses of depression and anxiety in breast cancer patients were less prevalent than expected based on our analysis of hospitalized breast cancer patients and matched non-breast cancer controls identified in the NIS dataset using ICD-9 diagnostic codes. Results suggest that under-diagnosis of mental health problems may be common among hospitalized women with a primary diagnosis of breast cancer. Future work may fruitfully explore reasons for, and consequences of, inappropriate identification of the mental health needs of breast cancer patients.

World War II-related post-traumatic stress disorder and breast cancer risk among Israeli women: a case-control study

BACKGROUND Several studies have suggested that post-traumatic stress disorder (PTSD) is related to adverse health outcomes. There are limited data on PTSD and cancer, which has a long latency period. We investigated the association between World War II (WWII)-related PTSD and subsequent breast cancer (BC) risk among Jewish WWII survivors and examined whether this association was modified by exposure to hunger during WWII. METHODS We compared 65 BC patients diagnosed in 2005 through 2010 to 200 population-based controls who were members of various organizations for Jewish WWII survivors in Israel. All participants were born in Europe, lived at least six months under Nazi rule during WWII, and immigrated to Israel after the war. We estimated PTSD using the PTSD Inventory and applied logistic regression models to estimate the association between WWII-related PTSD and BC, adjusting for potential confounders. RESULTS We observed a linear association between WWII-related PTSD and BC risk. This association remained significant following adjustment for potential confounders, including obesity, alcohol consumption, smoking, age during WWII, hunger exposure during WWII, and total number of traumatic life events (OR = 2.89, 95% CI = 1.14-7.31). However, the level of hunger exposure during WWII modified this effect significantly. CONCLUSIONS These findings suggest an independent association between WWII-related PTSD and subsequent BC risk in Jewish WWII survivors that is modified by hunger, a novel finding. Future research is needed to further explore these findings.

Correlations in global DNA methylation measures in peripheral blood mononuclear cells and granulocytes

Alterations in global DNA methylation levels have been associated with chronic diseases. Despite the increase in the number of studies measuring markers of global methylation, few have adequately examined within-individual differences by source of DNA and whether within-individual differences by source of DNA differ by age, race and other lifestyle factors. We examined correlations between peripheral mononuclear cell (PBMC) and granulocyte DNA methylation levels measured by the luminometric methylation assay (LUMA), and in LINE-1, Sat2, and Alu by MethyLight and pyrosequencing, in the same individual in 112 women participating in The New York City Multiethnic Breast Cancer Project. Levels of DNA methylation of Sat2 by MethyLight (r = 0.57; P < 0.01) and LINE-1 by pyrosequencing (r = 0.30; P < 0.01) were correlated between PBMC and granulocyte DNA of the same individuals, but LUMA and Alu levels were not. The magnitude of the correlations for Sat2 and LINE-1 varied when stratified by selected demographic and lifestyle factors, although the study sample size limited our comparisons across subgroups. These results lend further support to the importance of considering the source of DNA in epidemiologic studies of white blood cell DNA methylation. Results from studies that combine individuals with different available DNA sources need to be interpreted with caution.

Severe caloric restriction in young women during World War II and subsequent breast cancer risk

Aim:  The objective of the study was to examine the impact of WWII‐related caloric restriction (CR) on subsequent breast cancer (BC) risk based on individual exposure experiences and whether this effect was modified by age at exposure.

Association between body mass index and in-hospital outcomes: Analysis of the nationwide inpatient database.

Importance: Over one-third of American adults (36%) are obese and more than two-thirds (69%) are overweight. The impact of obesity on hospitalization outcomes is not well understood. Objective: To examine the association between body mass index (BMI) and overall, cancer, chronic obstructive pulmonary disease (COPD), asthma, and cardiovascular disease (CVD)-specific in-hospital mortality; postsurgical complications; and hospital length of stay (LOS). Design: Cross-sectional study. Setting: Representative sample of US hospitals included in the Health Cost and Utilization Project Nationwide Inpatient Sample database. Participants: We obtained data for patients admitted with a primary diagnosis of cancer, COPD, asthma, and CVD. Main Outcome: In-hospital mortality, postsurgical complications, and hospital LOS. Results: A total of 800,417 patients were included in this analysis. A higher proportion of Blacks (26.8%; 12.5%) and Whites (23.3%; 8.7%) had BMI of 40 to 49.9 and ≥50, respectively, compared with Hispanics (20.4%; 7.3%). Compared with normal BMI patients, the odds of in-hospital mortality increased 3.6-fold (odds ratio [OR] 3.62, 95% confidence interval [CI]: 3.37–3.89) for preobese patients, 6.5-fold (OR: 6.52, 95% CI: 5.79–7.34) for patients with BMI: 30 to 31.9, 7.5-fold (OR: 7.57, 95% CI: 6.67–8.59) for patients with BMI: 34 to 35.9, and 1.6- fold (OR: 1.77, 95% CI: 1.56–1.79) for patients with BMI ≥ 50. Compared with normal BMI patients, preobese and overweight patients had shorter hospital stays (&bgr; preobese: −1.58, 95% CI: −1.63, −1.52); however, no clear trends were observed for postsurgical complications. Conclusions: The majority of hospitalized patients in this analysis had a BMI > 30, and higher BMI was associated with increased risk of mortality and longer hospital stay.

Challenges in Recruiting Aging Women Holocaust Survivors to a Case Control Study of Breast Cancer

Older adults are underrepresented in medical research for many reasons, including recruitment difficulties. Recruitment of older adults for research studies is often a time-consuming process and can be more challenging when the study involves older adults with unique exposures to traumatic events and from minority groups. The current article provides a brief overview of (a) challenges encountered while recruiting aging women Holocaust survivors for a case control study and (b) strategies used for meeting those challenges. The case group comprised women Holocaust survivors who were recently diagnosed with breast cancer and the control group comprised healthy women from a Holocaust-survivor community in Israel.