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Objectives: To identify determinants of follow-up care and diagnosis of invasive cervical cancer among uninsured/underinsured women screened for cervical cancer., Methods: We examined the associations between health care facility, area-level, and individual-level factors on the outcomes of interest in retrospective cohort of women from the New Jersey Cancer Education and Early Detection Program (2000-2015)., Results: Women screened at department of health clinics (aOR:3.11, 95% CI: 2.30-4.20) and health care system-affiliated clinics (aOR:1.71, 95% CI: 1.11-2.64) had higher odds of lacking follow-up care compared with women in private physician practices. Similarly, women residing in areas with the highest unemployment had higher odds of lacking follow-up (aOR:1.48, 95% CI: 1.07-2.06). Delays in follow-up care were higher for women born in Central/South American countries compared with U.S.-born women (aOR: 1.46, 95% CI: 1.12-1.92)., Conclusions: Improved outreach efforts and multilevel strategies are needed to address the persistent barriers to appropriate follow-up care for underserved women.

Background: Rural residents in the U.S., particularly residents of Appalachia, are underrepresented in biomedical research, limiting the generalizability of research findings., Objective: To examine factors associated with Appalachian adults' willingness to participate in biospecimen donation and banking., Methods: A survey assessing willingness to donate blood, saliva, and buccal specimens and to have these biospecimens stored for future use in genetic studies was conducted among 493 Appalachian adults., Results: Most participants 73% (358/493) were willing to donate one or more biospecimen type; among them, 75% (268/358) were willing to donate blood, saliva, and buccal specimens. Approximately 61% (300/493) were willing to have their biospecimens banked and 97% (290/300) of these were willing to have their samples used for genetic studies. Appalachian self-identity predicted willingness to donate biospecimens, to have them stored, and used in genetic studies (OR1.52, 95% CI 1.03-2.24)., Conclusions: Appalachian adults were generally willing to participate in biobanking research.

Despite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAm's. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA-BRCA data were used for replication. 1,214 aDNAm's were identified; 97% with increased methylation, and all on autosomes. Sites with increased methylation were predominantly in CpG lslands and non-enhancers. aDNAm's with decreased methylation were generally located in intergenic regions, non-CpG Islands, and enhancers. Of the aDNAm's identified, 650 are known to be involved in cancer, including ESR1 and beta-estradiol responsive genes. Expression of DNMT3A was positively associated with age. Two aDNAm's showed borderline significant associations with DNMT3A expression; KRR1 (OR 6.57, 95% CI: 2.51-17.23) and DHRS12 (OR 6.08, 95% CI: 2.33-15.86). A subset of aDNAm's co-localized within vulnerable regions for somatic mutations in cancers including breast cancer. Expression of C19orf48 was inversely and significantly correlated with its methylation level. In the TCGA dataset, 84% and 64% of the previously identified aDNAm's were correlated with age in both normal-adjacent and tumor breast tissues, with differential associations by histological subtype. Given the similarity of findings in the breast tissues of healthy women and breast tumors, aDNAm's may be one pathway for increased breast cancer risk with age., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Background: Social isolation is an important determinant of all-cause mortality, with evidence suggesting an association with cancer-specific mortality as well. In this study, we examined the associations between social isolation and neighborhood poverty (independently and jointly) on cancer mortality in a population-based sample of US adults., Methods: Using data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994), NHANES III Linked Mortality File (through 2011) and 1990 Census, we estimated the relationship between social isolation and high neighborhood poverty and time-to-cancer death using multivariable-adjusted Cox proportional hazards models. We examined the associations of each factor independently and explored the multiplicative and additive interaction effects on cancer mortality risk and also analyzed these associations by sex., Results: Among 16 044 US adults with 17-23 years of follow-up, there were 1133 cancer deaths. Social isolation (HR 1.25, 95% CI: 1.01-1.54) and high neighborhood poverty (HR 1.31, 95% CI: 1.08-1.60) were associated with increased risk of cancer mortality adjusting for age, sex, and race/ethnicity; in sex-specific estimates this increase in risk was evident among females only (HR 1.39, 95% CI: 1.04-1.86). These associations were attenuated upon further adjustment for socioeconomic status. There was no evidence of joint effects of social isolation and high neighborhood poverty on cancer mortality overall or in the sex-stratified models., Conclusions: These findings suggest that social isolation and higher neighborhood poverty are independently associated with increased risk of cancer mortality, although there is no evidence to support our a priori hypothesis of a joint effect.

Background: Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer., Results: A 41-miRNA model distinguished breast cancer risk in the discovery study (accuracy of 83.3%), which was replicated in the independent study (accuracy = 63.4%, P=0.09). Among the 41 miRNA, 20 miRNAs were detectable in serum, and predicted breast cancer occurrence within 18 months of blood draw (accuracy 53%, P=0.06). These risk-related miRNAs were enriched for HER-2 and estrogen-dependent breast cancer signaling., Materials and Methods: MiRNAs were assessed in two cross-sectional studies of women without breast cancer and a nested case-control study of breast cancer. Using breast tissues, a multivariate analysis was used to model women with high and low breast cancer risk (based upon Gail risk model) in a discovery study of women without breast cancer (n=90), and applied to an independent replication study (n=71). The model was then assessed using serum samples from the nested case-control study (n=410)., Conclusions: Studying breast tissues of women without breast cancer revealed miRNAs correlated with breast cancer risk, which were then found to be altered in the serum of women who later developed breast cancer. These results serve as proof-of-principle that miRNAs in women without breast cancer may be useful for predicting breast cancer risk and/or as an adjunct for breast cancer early detection. The miRNAs identified herein may be involved in breast carcinogenic pathways because they were first identified in the breast tissues of healthy women.

Aims: The definition of tumour deposit (TD) in colorectal cancer (CRC) was changed recently in the American Joint Commission on Cancer (AJCC) Staging Manual, 7th edition. We aimed to examine the prognostic values of the newly defined TD and perineural invasion (PNI) in this population study., Methods and Results: We identified the incidental CRC cases with known TD or PNI status in the Surveillance, Epidemiology, and End Results (SEER) programme diagnosed in 2010 and 2011. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to estimate overall survivals (OS) and cancer-specific survival (CSS). We found that 6.71% (2774 of 41 323) of the CRC cases were positive for TD and 9.61% (3970 of 41 215) positive for PNI. In multivariable models, TD- and PNI-positive statuses correlated independently with worse 3-year OS [hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.58-1.80 and HR: 1.24, 95%: CI: 1.16-1.32, respectively] and 3-year CSS (HR: 1.79, 95% CI: 1.65-1.94 and HR: 1.28, 95% CI: 1.18-1.38, respectively, P < 0.001 for all). Other independent prognostic factors included age, T category, N category, tumour location and tumour grade, but not gender. TD and PNI correlated with worse OS in all N categories (P < 0.001 for all). TD-associated HR for 3-year OS increases as the N category becomes lower (1.73 in N2, 2.32 in N1 and 3.24 in N0), while rare (1.4%) TD-positive CRC in N0 category should have been assigned to N1c., Conclusions: Tumour deposit and PNI correlate independently with worse 3-year OS and CSS. TD appears prognostically more important in the CRC of lower N categories., (© 2016 John Wiley & Sons Ltd.)

Single nucleotide polymorphisms (SNPs) in one-carbon metabolism genes and lifestyle factors (alcohol drinking and breast folate) may be determinants of whole-genome methylation in the breast. DNA methylation profiling was performed using the Illumina Infinium HumanMethylation450 BeadChip in 81 normal breast tissues from women undergoing reduction mammoplasty and no history of cancer. ANCOVA, adjusting for age, race and BMI, was used to identify differentially-methylated (DM) CpGs. Gene expression, by the Affymetrix GeneChip Human Transcriptome Array 2.0, was correlated with DM. Biological networks of DM genes were assigned using Ingenuity Pathway Analysis. Fifty-seven CpG sites were DM in association with eight SNPs in FTHFD, MTHFD1, MTHFR, MTR, MTRR, and TYMS (P <5.0 x 10 -5 ); 56% of the DM CpGs were associated with FTHFD SNPs, including DM within FTHFD. Gene expression was negatively correlated with FTHFD methylation (r=-0.25, P=0.017). Four DM CpGs identified by SNPs in MTRR, MTHFR, and FTHFD were significantly associated with alcohol consumption and/or breast folate. The top biological network of DM CpGs was associated with Energy Production, Molecular Transportation, and Nucleic Acid Metabolism. This is the first comprehensive study of the association between SNPs in one-carbon metabolism genes and genome-wide DNA methylation in normal breast tissues. These SNPs, especially FTHFD, as well as alcohol intake and folate exposure, appear to affect DM in breast tissues of healthy women. The finding that SNPs in FTHFD and MTR are associated with their own methylation is novel and highlights a role for these SNPs as cis-methylation quantitative trait loci., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: As social media becomes increasingly popular online venues for engaging in communication about public health issues, it is important to understand how users promote knowledge and awareness about specific topics., Objective: The aim of this study is to examine the frequency of discussion and differences by race and ethnicity of cancer-related topics among unique users via Twitter., Methods: Tweets were collected from April 1, 2014 through January 21, 2015 using the Twitter public streaming Application Programming Interface (API) to collect 1% of public tweets. Twitter users were classified into racial and ethnic groups using a new text mining approach applied to English-only tweets. Each ethnic group was then analyzed for frequency in cancer-related terms within user timelines, investigated for changes over time and across groups, and measured for statistical significance., Results: Observable usage patterns of the terms "cancer", "breast cancer", "prostate cancer", and "lung cancer" between Caucasian and African American groups were evident across the study period. We observed some variation in the frequency of term usage during months known to be labeled as cancer awareness months, particularly September, October, and November. Interestingly, we found that of the terms studied, "colorectal cancer" received the least Twitter attention., Conclusions: The findings of the study provide evidence that social media can serve as a very powerful and important tool in implementing and disseminating critical prevention, screening, and treatment messages to the community in real-time. The study also introduced and tested a new methodology of identifying race and ethnicity among users of the social media. Study findings highlight the potential benefits of social media as a tool in reducing racial and ethnic disparities.

There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω-3PUFA with breast tissue LCω-3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross-sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C-reactive protein (CRP), interleukin (IL)-6 and IL-8 in plasma and tissue were measured by ELISA. Multivariable-adjusted regression models were used to estimate associations between erythrocyte LCω-3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω-3PUFA tertile had LCω-3PUFA concentrations in the breast 73% (95% CI: 31-128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω-3PUFA were similar in magnitude. No significant association was found for the shorter ω-3 PUFA, α-linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: -23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω-3 PUFA and tissue IL-6 or IL-8 concentrations. Our findings provide evidence that erythrocyte ω-3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω-3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication., (© 2015 UICC.)

Purpose: This study examines the factors distinguishing breast cancer (BC) subtypes., Methods: We examined subtypes in 629 women with invasive BC, diagnosed from 2006 to 2012, and enrolled in an epidemiological study in New Jersey. Using molecular characteristics from pathology reports, BCs were categorized as luminal A, luminal B, non-luminal HER2-expressing, or triple-negative breast cancer (TNBC) subtypes. Multinomial logistic models (luminal A as referent) were used to describe BC subtype associations., Results: Women with luminal B tumors were more likely to be younger at diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.4] and to have higher-grade (OR 2.6, 95% CI 1.5-4.7), larger (OR 1.9, 95% CI 1.0-3.6), and Ki67-positive tumors (OR 2.1, 95% CI 1.1-4.0). Women with non-luminal HER2-expressing BCs were more likely to have higher-grade tumors (OR 14.5, 95% CI 5.3-39.7). Women with TNBCs were more likely to be African-American (OR 1.9, 95% CI 1.0-3.4) and to have higher-grade (OR 9.7, 95% CI 5.1-18.4), larger (OR 2.2, 95% CI 1.0-4.8), and Ki67-positive (OR 2.9, 95% CI 1.6-5.2) tumors. Notably, compared to the luminal A subtype, luminal B, non-luminal HER2-expressing, and triple-negative subtypes were more frequently self-detected; however, these associations were attenuated in multivariable models., Conclusions: These findings suggest that some BC subtypes were associated with features denoting more aggressive phenotypes, namely higher grade, larger size, and Ki67 positivity, and possibly patient self-detection among some women. These findings highlight a need for enhanced screening, particularly among younger women, racial/ethnic minorities, and lower socioeconomic subgroups.

Background: Patient navigation may reduce cancer disparities associated with socioeconomic status (SES) and household factors. This study examined whether these factors were associated with delays in diagnostic resolution among patients with cancer screening abnormalities and whether patient navigation ameliorated these delays., Methods: This study analyzed data from 5 of 10 centers of the National Cancer Institute's Patient Navigation Research Program, which collected SES and household data on employment, income, education, housing, marital status, and household composition. The primary outcome was the time to diagnostic resolution after a cancer screening abnormality. Separate adjusted Cox proportional hazard models were fit for each SES and household factor, and an interaction between that factor and the intervention status was included., Results: Among the 3777 participants (1968 in the control arm and 1809 in the navigation intervention arm), 91% were women, and the mean age was 44 years; 43% were Hispanic, 28% were white, and 27% were African American. Within the control arm, the unemployed experienced a longer time to resolution than those employed full-time (hazard ratio [HR], 0.85; P = .02). Renters (HR, 0.81; P = .02) and those with other (ie, unstable) housing (HR, 0.60; P < .001) had delays in comparison with homeowners. Never married (HR, 0.70; P < .001) and previously married participants (HR, 0.85; P = .03) had a longer time to care than married participants. There were no differences in the time to diagnostic resolution with any of these variables within the navigation intervention arm., Conclusions: Delays in diagnostic resolution exist by employment, housing type, and marital status. Patient navigation eliminated these disparities in the study sample. These findings demonstrate the value of providing patient navigation to patients at high risk for delays in cancer care., (© 2015 American Cancer Society.)

Unlabelled: Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates (, Incidence: 66.96;, Mortality: 30.82 per 100,000) compared to women of East Indian (, Incidence: 41.04, MORTALITY: 14.19 per 100,000) or mixed ancestry (, Incidence: 36.72, MORTALITY: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well-known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations) that is informed by public health needs and contextual realities of the nation., Competing Interests: None.

Background: Limited data are available on the association between colorectal cancer (CRC) worry and CRC screening uptake, particularly in rural and underserved populations where there is an excess burden of CRC., Methods: Between September 2009 and March 2010, we conducted a cross-sectional study among a randomly selected sample of Appalachian Ohio residents aged 51-75 years (n= 1084). We also reviewed their medical records. Multivariable-adjusted models examined the association between CRC worry and screening by medical record review, assessed effect modification by CRC worry and determined the correlates of higher CRC worry., Results: Approximately 50% of participants were adherent to CRC screening guidelines. There was no significant association between higher CRC worry and screening adherence [odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.86-2.02]. CRC worry did not modify the association between any covariate and screening adherence. Participants who were unemployed/disabled (OR = 2.15, 95% CI: 1.34-3.45) and had higher CRC risk perception (OR = 3.49, 95% CI: 2.19-5.56) had higher odds of moderate-to-extreme worry., Conclusions: These findings highlight the need for meaningful exploration of why higher CRC worry is not associated with adherence to CRC screening, particularly in rural, medically underserved populations. Development and implementation of interventions to increase CRC screening in such areas is a significant public health priority., (© The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

p16(INK4a) is a tumor suppressor gene, frequently hypermethylated in breast cancer; this epigenetic silencing of p16(INK4a) occurs early in carcinogenesis. The risk factors and functional consequences of p16(INK4a) methylation are unknown. Alcohol consumption, a breast cancer risk factor, impedes folate metabolism and may thereby alter gene methylation since folate plays a pivotal role in DNA methylation. In a cross-sectional study of 138 women with no history of breast cancer who underwent reduction mammoplasty, we studied breast cancer risk factors, plasma and breast folate concentrations, variation in one-carbon metabolism genes, p16(INK4a) promoter methylation and P16 protein expression. Logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). p16(INK4a) methylation was negatively correlated with P16 expression (r = -0.28; P = 0.002). Alcohol consumption was associated with lower breast folate (P = 0.03), higher p16(INK4a) promoter methylation (P = 0.007) and less P16 expression (P = 0.002). Higher breast folate concentrations were associated with lower p16(INK4a) promoter methylation (P = 0.06). Genetic variation in MTRR (rs1801394) and MTHFD1 (rs1950902) was associated with higher p16 (INK4a) promoter methylation (OR = 2.66, 95% CI: 1.11-6.42 and OR = 2.72, 95% CI: 1.12-6.66, respectively), whereas variation in TYMS (rs502396) was associated with less P16 protein expression (OR = 0.22, 95% CI: 0.05-0.99). Given that this is the first study to indicate that alcohol consumption, breast folate and variation in one-carbon metabolism genes are associated with p16(INK4a) promoter methylation and P16 protein expression in healthy tissues; these findings require replication., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n = 61) and AAs (n = 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.

Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility.

Background: The effect of neighborhood and healthcare access factors on cancer outcomes among patients enrolled in navigator programs is not clearly understood. This study assessed associations between: (i) neighborhood factors and diagnostic time to resolution (TTR) and (ii) geographic access and TTR following an abnormal breast or cervical cancer screening test among women participating in the Ohio Patient Navigator Research Program (OPNRP)., Methods: Patient (demographic, socioeconomic status, home-to-clinic distance) and neighborhood (deprivation, racial segregation) characteristics of 801 women living in one of 285 census tracts (CT) in greater Columbus, Ohio were examined. Randomization to receive navigation occurred at the clinic level. Multilevel Cox regression and spatial analysis were used to estimate effects of various factors on TTR and assess model assumptions, respectively., Results: TTR increased as neighborhood deprivation increased. After adjustment for age, friend social support, education, and healthcare status, the TTR among women living in a neighborhood with a moderate median household income (between $36,147 and $53,099) was shorter compared with women living in low median household income neighborhoods (<$36,147; P < 0.05). There is little evidence that unmeasured confounders are geographically patterned., Conclusions: Increased neighborhood socioeconomic deprivation was associated with longer TTR following an abnormal breast or cervical cancer screening test., Impact: These results highlight the need for addressing patient- and neighborhood-level factors to reduce cancer disparities among underserved populations., (©2014 American Association for Cancer Research.)

Background: Circulating adipokines may be associated with breast cancer risk. Genetic variants governing adipokines and adipokine receptors may also predict risk, but their effect on breast adipokine concentrations is unknown., Methods: We conducted a cross-sectional analysis of functional SNPs in 5 adipokine genes [adiponectin, leptin (LEP), and their receptors] among 85 cancer-free women who were undergoing reduction mammoplasty., Results: In multivariable-adjusted regression models, compared with the common GG genotype, the AA genotype of the LEP A19G SNP was associated with 27% lower plasma adiponectin [ratio, 0.73; 95% confidence interval (CI), 0.54-0.98] and leptin (ratio, 0.73; 95% CI, 0.55-0.96). Women with the AG genotype of LEP A19G had 39% lower breast leptin (ratio, 0.61; 95% CI, 0.39-0.97) compared with those with the GG genotype. No associations were observed for SNPs in the remaining genes., Conclusions: Genetic variation in LEP may alter endogenous adipokine concentrations in circulation and in breast tissues., Impact: These preliminary findings may support the hypothesis that genetic variation in adipokine genes modifies circulating adipokine concentrations and possibly leptin concentrations in local breast tissues, which may be associated with breast cancer risk., (©2014 American Association for Cancer Research.)

Background: The high prevalence of obesity in America can be attributed to inadequate energy expenditure as a result of high levels of physical inactivity. This review presents an overview of the current literature on physical activity, specifically through active videogame systems (exergaming) and how these systems can help to increase physical activity levels., Methods: The search strategy for this review was to identify previous studies that investigated energy expenditure levels using a single active video game or a combination of active videogames., Results: Based on data from 27 studies, a strong correlation exists between exergaming and increased energy expenditure (up to 300% above resting levels). The majority of active videogames tested were found to achieve physical activity levels of moderate intensity, which meet American College of Sports Medicine guidelines for health and fitness., Conclusions: Exergaming is a new and exciting strategy to potentially improve physical activity levels and reduce obesity among Americans.

Purpose: The most effective dietary pattern for breast cancer prevention has been greatly debated in recent years. Studies have examined hypocaloric diets, with particular emphasis on macronutrient composition, yielding inconclusive data. The objective of this study was to examine the effects of calorie-restricted low-fat and low-carbohydrate diets (LFD and LCD, respectively) on circulating adipokines among overweight and obese premenopausal women., Methods: Seventy-nine overweight and obese premenopausal women were randomized to either LFD or LCD, with increased physical activity, for 52 weeks. Serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L) were measured at baseline, and at weeks 34 and 52 to assess intervention effects., Results: While there were no significant changes in serum adiponectin concentrations following the LCD and LFD interventions, leptin concentrations significantly decreased by week 34 of the intervention period (LCD: 35.3%, P = 0.004; LFD: 30.0%, P = 0.01), with no difference by intervention arm. At week 52, these reductions were statistically non-significant, indicating a return to baseline levels by the end of the intervention. While there were non-significant increases in the A/L ratio following the LCD and LFD intervention arms, the overall trend, across groups, was marginally significant (P = 0.05) with increases of 16.2% and 35.1% at weeks 34 and 52, respectively., Conclusions: These findings suggest that caloric-restricted LCD and LFD dietary patterns favorably modify leptin and possibly the A/L ratio, and lend support to the hypothesis that these interventions may be effective for obesity-related breast cancer prevention through their effects on biomarkers involved in metabolic pathways., Clinical Trial Registration Number: NCT01559194.

Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin, and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m(2) or >30 kg/m(2)) and randomized to a 12-week, two-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were IVR + coach and IVR + no-coach condition. Pre-post changes in serum adiponectin, leptin, and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95 % confidence intervals [CI]) corresponding to postintervention adipokine concentrations relative to preintervention concentrations. While postintervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (ratio = 0.86, 95 % CI 0.74-1.01, and ratio = 0.94, 95 % CI 0.87-1.01, respectively) and increase in A/L ratio = 1.09, 95 % CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention.

Context: Breast cancer risk among postmenopausal women increases as body mass index increases. Practical preventive methods to reduce risk of breast cancer are lacking. Few studies have investigated the effects of carotenoids and isoflavones on circulating adipokines in postmenopausal women., Objective: The aim was to examine the effects of lycopene- and isoflavone-rich diets on serum adipokines., Design: This was a 26-week, two-arm, longitudinal crossover trial., Setting: Participants were recruited from clinics at The Ohio State University Comprehensive Cancer Center., Participants: Seventy postmenopausal women at increased breast cancer risk participated in the study. The mean age and body mass index of participants was 57.2 years and 30.0 kg/m(2), respectively; the study was comprised of 81.4% whites., Interventions: The interventions included 10 weeks of consumption of a tomato-based diet (≥25 mg lycopene daily) and 10 weeks of consumption of a soy-based diet (≥40 g of soy protein daily), with a 2-week washout in between., Main Outcome Measures: Changes in serum adiponectin, leptin, and the adiponectin to leptin ratio were examined for each intervention through linear mixed models, with ratio estimates corresponding to postintervention adipokine concentrations relative to preintervention concentrations., Results: After the tomato intervention, among all women, adiponectin concentration increased (ratio 1.09, 95% confidence interval (CI) 1.00-1.18), with a stronger effect observed among nonobese women (ratio 1.13, 95% CI 1.02-1.25). After the soy intervention, adiponectin decreased overall (ratio 0.91, 95% CI 0.84-0.97), with a larger reduction observed among nonobese women (ratio 0.89, 95% CI 0.81-0.98). Overall, no significant changes in leptin or the adiponectin to leptin ratio were observed after either intervention., Conclusions: Increasing dietary consumption of tomato-based foods may beneficially increase serum adiponectin concentrations among postmenopausal women at increased breast cancer risk, especially those who are not obese. Additional studies are essential to confirm these effects and to elucidate the specific mechanisms that may make phytonutrients found in tomatoes practical as breast cancer chemopreventive agents.

Purpose: This study assessed the levels of depressive symptomatology in African-American women with breast cancer compared to those of women without breast cancer and examined demographic, psychosocial, and clinical factors correlated with depression., Methods: A total of 152 African-American women were recruited from Washington, DC and surrounding suburbs. Breast cancer patients (n = 76 cases) were recruited from a health care center and women without cancer were recruited from health fairs (n = 76 comparison). We assessed depression, psychosocial variables (ego strength and social support), and sociodemographic factors from in-person interviews. Stage and clinical factors were abstracted from medical records. Independent sample t test, chi square test, analyses of variance, and multiple regression models were used to identify differences in depression and correlates of depression among the cases and comparison groups., Results: Women with breast cancer reported significantly greater levels of depression (m = 11.5, SD = 5.0) than women without breast cancer (m = 3.9, SD = 3.8) (p < 0.001). Higher cancer stage (beta = 0.91) and higher age (beta = 0.11) were associated with depression in the breast patients, explaining 84 % of the variance. In the comparison group, ego strength and tangible support were inversely associated with depressive symptoms, accounting for 32 % of the variance., Conclusions: Women with more advanced disease may require interdisciplinary approaches to cancer care (i.e., caring for the whole person)., Implications for Cancer Survivors: Depression is often underrecognized and undertreated in African-American breast cancer patients. Understanding the factors related to depression is necessary to integrate psychosocial needs to routine cancer care to improve survivors' quality of life.

There is an excess burden of colorectal cancer (CRC) in the Appalachian region of the United States, which could be reduced by increased uptake of CRC screening tests. Thus, we examined correlates of screening among Appalachian residents at average-risk for CRC. Using a population-based sample, we conducted interviews with and obtained medical records of Appalachian Ohio residents 51-75 years between September 2009 and April 2010. Using multivariable logistic regression, we identified correlates of being within CRC screening guidelines by medical records. About half of participants were within CRC screening guidelines. Participants who were older (OR = 1.04, 95 % CI 1.01, 1.07), had higher income ($30,000-$60,000, OR = 1.92, 95 % CI 1.29, 2.86; ≥$60,000, OR = 1.80, 95 % CI 1.19, 2.72), a primary care provider (OR = 4.22, 95 % CI 1.33, 13.39), a recent check-up (OR = 2.37, 95 % CI 1.12, 4.99), had been encouraged to be screened (OR = 1.57, 95 % CI 1.11, 2.22), had been recommended by their doctor to be screened (OR = 6.68, 95 % CI 3.87, 11.52), or asked their doctor to order a screening test (OR = 2.24, 95 % CI 1.36, 3.69) had higher odds of being screened within guidelines in multivariable analysis. Findings suggest that access to and utilization of healthcare services, social influence, and patient-provider communication were the major factors associated with CRC screening. Researchers and healthcare providers should develop and implement strategies targeting these barriers/facilitators to improve CRC screening rates and reduce the CRC burden among residents of Appalachia.

Objectives: We determined the validity of self-reported colorectal cancer (CRC) screening data provided by Appalachian Ohio residents and identified correlates of providing accurate data., Design and Sample: We conducted cross-sectional telephone interviews between September 2009 and April 2010. Our study included Appalachian Ohio residents (n = 721) ages 51-75 years., Measures: We compared self-reported CRC screening data to medical records to determine validity. Multivariable logistic regression was used to identify correlates of providing accurate self-reported screening data., Results: About 68% of participants self-reported having any CRC screening test within recommended guidelines, whereas medical records indicated that only 49% were within guidelines (concordance = 0.76). Concordance was higher for flexible sigmoidoscopy and fecal occult blood test compared with colonoscopy, although sensitivity and positive predictive value were much higher for colonoscopy. Participants overreported CRC screening behaviors for all tests. Participants who had a regular checkup in the last 2 years (OR = 2.78, 95% CI: 1.15-6.73), or who self-rated their health as good or better (OR = 1.88, 95% CI: 1.12-3.16) were more likely to provide accurate screening data., Conclusions: Many participants failed to provide accurate CRC screening data, and validity varied greatly across individual CRC screening tests. Future CRC screening studies among Appalachian residents should use medical records, if possible, to determine screening histories., (© 2013 Wiley Periodicals, Inc.)

We investigated insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 concentrations in histologically normal breast tissues and assessed their association with plasma concentrations, and breast cancer risk factors. IGF-1 and IGFBP-3 were assessed in plasma and breast tissues of 90 women with no history of any cancer and undergoing reduction mammoplasty. Pearson correlations and ANOVAs were used to describe plasma-breast associations and biomarker differences by breast cancer risk factors, respectively. Multivariable regression models were used to determine associations between risk factors, and breast IGF-1 and IGFBP-3. The mean age of the study sample was 37.3 years, 58 % were white, and generally these women were obese (mean BMI = 30.8 kg/m(2)). We observed no plasma-breast correlation for IGF-1, IGFBP-3, or IGF-1/IGFBP-3 (r = -0.08, r = 0.14, and r = 0.03, respectively; p-values >0.05). Through age- and BMI-adjusted analysis, BMI and years of oral contraceptive (OC) use were inversely associated with breast IGF-1 (p-values = 0.02 and 0.003, respectively) and age was associated with breast IGFBP-3 (p = 0.01), while breast IGF-1/IGFBP-3 was higher in blacks than whites (1.08 vs. 0.68, p = 0.04) and associated with age and BMI (p-values = 0.03 and 0.002, respectively). In multivariable-adjusted models, some breast cancer risk factors studied herein explained 24, 10, and 15 % of the variation in breast IGF-1, IGFBP-3, and IGF-1/IGFBP-3, respectively. While reasons for the lack of plasma-breast hormone correlations in these cancer-free women are unknown, several factors were shown to be associated with breast concentrations. The lack of correlation between blood and tissue IGF-1 and IGFBP-3 suggests that studies of breast cancer risk assessing blood IGF-1 and IGFBP-3 may have important limitations in understanding their role in breast carcinogenesis.

Background: Blood adipokines are associated with breast cancer risk; however, blood-breast adipokine correlations and factors that explain variation in adipokines are unknown., Methods: Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations., Results: Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma-breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma-breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin., Conclusions: Although we report positive plasma-breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis., Impact: A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues., (2012 AACR)

Background: Lipid levels, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, have been reported to be associated with breast cancer risk., Methods: We studied African American women (97 breast cancer cases and 102 controls) accrued through a population-based, case-control study in the Washington, DC metropolitan area during 1997 and 1998. Plasma lipid levels were measured using enzymatic methods. Logistic regressions (adjusted for age, age at menarche, parity, previous alcohol consumption, and education) were used to explore the associations between lipid levels and breast cancer., Results: Through multivariable-adjusted regression, we observed a significant inverse association between breast cancer risk and increasing levels of total cholesterol (OR=.46, 95% Cl = .25-.85) and LDL (OR = .41, 95% CI = .21-.81), whereas lower levels of HDL were associated with a significant increase in risk (OR = 1.99, 95% CI = 1.06-3.74)., Conclusions: Our data demonstrate significant reductions in breast cancer risk with high levels of total cholesterol and significant increase in risk when HDL levels are low. These data are in support of a protective effect of cholesterol which has been reported in other populations; further, these findings add to the literature in an understudied population, African American women.

Background: Complementary 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., Methods: A cohort study of breast cancer survivors, who completed the 1999 Black Women's 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., Results: A 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)., Conclusions: A 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.

Objective: Determining Costa Ricans' behaviour patterns when using health services., Methods: The Costa Rican Health Survey was used. Central tendency, dispersion, percentages, frequencies, Ji-Square and Kruskal-Walis test measurements were analysed., Results: Area of residence and income level were the predisposing factors in both out-patient and emergency services whereas educational level was so in terms of hospitalisation service. Health insurance status and the area of residence were the enabling factors associated with using out-patient and hospitalisation services. The need factors associated with outpatient services were the individuals' perceived state of health, having remained in bed at least until noon and suffering some chronic disease; chronic disease was associated with hospitalisation and remaining in bed when using the emergency service., Discussion: Most variables postulated by Andersen and Newman's model as being determinants for using health services were present in Costa Rica. Nevertheless, the significance of its factors varied between outpatient, hospitalisation and emergency services.