Search

Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor approved to treat type 2 diabetes mellitus (T2DM), among other conditions. When dapagliflozin was approved in Europe for treating T2DM (2012), potential safety concerns regarding its effect on kidney function resulted in this post-authorization safety study to assess hospitalization for acute kidney injury (hAKI) among dapagliflozin initiators in a real-world setting.The aim of this study was to evaluate the incidence of hAKI in adults with T2DM initiating dapagliflozin compared with other glucose-lowering drugs (GLDs).This noninterventional cohort study identified new users of dapagliflozin and comparator GLDs from November 2012 to February 2019 from three longitudinal, population-based data sources: Clinical Practice Research Datalink (CPRD; United Kingdom), the HealthCore Integrated Research Database (HIRD; United States [US]), and Medicare (US). Electronic algorithms identified occurrences of hAKI, from which a sample underwent validation. Incidence rates for hAKI were calculated, and incidence rate ratios (IRRs) compared hAKI in dapagliflozin with comparator GLDs. Propensity score trimming and stratification were conducted for confounding adjustment.In all data sources, dapagliflozin initiators had a lower hAKI incidence rate than comparator GLD initiators (adjusted IRRs: CPRD, 0.44 [95% confidence interval (CI), 0.22-0.86]; HIRD, 0.76 [95% CI, 0.62-0.93]; Medicare, 0.69 [95% CI, 0.59-0.79]). The adjusted IRR pooled across the data sources was 0.70 (95% CI, 0.62-0.78). Results from sensitivity and stratified analyses were consistent with the primary analysis.This study, with34,000 person-years of real-world dapagliflozin exposure, suggests a decreased risk of hAKI in patients with T2DM exposed to dapagliflozin, aligning with results from dapagliflozin clinical trials.European Union Post-Authorisation Studies Register, EUPAS 11684; ClinicalTrials.gov, NCT02695082.

At the time of dapagliflozin's approval in Europe (2012) to treat patients with type 2 diabetes mellitus, concerns regarding acute liver injury and severe complications of urinary tract infection (sUTI) led to two post-authorization safety (PAS) studies of these outcomes to monitor the safety of dapagliflozin in real-world use.To investigate the incidence of hospitalization for acute liver injury (hALI) or sUTI (pyelonephritis or urosepsis) among patients initiating dapagliflozin compared with other glucose-lowering drugs (GLDs).These two noninterventional cohort studies identified initiators of dapagliflozin and comparator GLDs in November 2012-February 2019 using data from three longitudinal, population-based data sources: Clinical Practice Research Datalink (UK), the HealthCore Integrated Research Database (USA), and the Medicare database (USA). Outcomes (hALI and sUTI) were identified with electronic algorithms. Incidence rates were estimated by exposure group. Incidence rate ratios (IRRs) were calculated comparing dapagliflozin to comparator GLDs, using propensity score trimming and stratification to address confounding. The sUTI analyses were conducted separately by sex.In all data sources, hALI and sUTI incidence rates were generally lower in dapagliflozin initiators than comparator GLD initiators. The adjusted IRR (95% confidence interval) pooled across data sources for hALI was 0.85 (0.59-1.24) and for sUTI was 0.76 (0.60-0.96) in females and 0.74 (0.56-1.00) in males. Findings from sensitivity analyses were largely consistent with the primary analyses.These real-world studies do not suggest increased risks of hALI or sUTI, and they suggest a potential decreased risk of sUTI with dapagliflozin exposure compared with other GLDs.

BackgroundPatients with breast cancer who overexpress the human epidermal growth factor receptor 2 (HER2) and subsequently develop brain metastasis (BM) typically experience poor quality of life and low survival. We conducted a comprehensive literature review to identify prognostic factors for BM and predictors of survival after developing BM, and the effects of therapies with different mechanisms of action among patients with HER2+ breast cancer (BC).MethodsA prespecified search strategy was used to identify research studies investigating BM in patients with HER2+ BC published in English during January 1, 2009–to June 25, 2021. Articles were screened using a two-phase process, and data from selected articles were extracted.ResultsWe identified 25 published articles including 4097 patients with HER2+ BC and BM. Prognostic factors associated with shorter time to BM diagnosis after initial BC diagnosis included younger age, hormone receptor negative status, larger tumor size or higher tumor grade, and lack of treatment with anti-HER2 therapy. Factors predictive of longer survival after BM included having fewer brain lesions (ConclusionsMore research is needed to better understand risk factors for BM and survival after BM in the context of HER2+ BC, as well as the assessment of new anti-HER2 therapy regimens that may provide additional therapeutic options for BM in these patients.

Purpose Anti-human epidermal growth factor receptor 2 (HER2) therapies are associated with interstitial lung disease (ILD), also referred to as pneumonitis. In this literature review, we describe the incidence of ILD among patients with HER2-positive metastatic breast cancer (MBC) receiving anti-HER2 therapies, and we describe existing recommendations for monitoring and managing drug-induced ILD among these patients. Methods We searched PubMed and Embase to identify clinical trials and postmarket observational studies that investigated anti-HER2 therapies for HER2-positive MBC, reported on ILD, and were published during January 1, 2009 to July 15, 2019. Articles were screened by two researchers; data were extracted from the full-text articles. Results The 18 articles selected for this review assessed 9,886 patients who received trastuzumab (8 articles), lapatinib (4 articles), trastuzumab emtansine (3 articles), trastuzumab deruxtecan (2 articles), or trastuzumab duocarmazine (1 article). The overall incidence of all-grade ILD was 2.4% (n = 234), with 66.7% (n = 156) occurring as grade 1–2 events, 0.5% grade 3–4 (n = 54; incidence), and 0.2% grade 5 (n = 16; incidence). The highest ILD incidence (21.4%) was among patients receiving trastuzumab combined with everolimus and paclitaxel. Ten studies indicated that ILD events were managed via dose interruption, dose reduction, or treatment discontinuation; two studies included detailed guidelines on managing drug-induced ILD. Conclusions ILD is a well-described adverse drug reaction associated with several anti-HER2 drugs. Published ILD management guidelines are available for few anti-HER2 treatment regimens; however, guidance for monitoring for anti-HER2 drug-induced ILD is lacking.

The ETS family of transcription factors is involved in several normal remodeling events and pathological processes including tumor progression. ETS transcription factors are divided into subfamilies based on the sequence and location of the ETS domain. ETV5 (Ets variant gene 5; also known as ERM) is a member of the PEA3 subfamily. Our meta-analysis of normal, benign, and malignant thyroid samples demonstrated that ETV5 expression is upregulated in papillary thyroid cancer and was predominantly associated with BRAF V600E or RAS mutations. However, the precise role of ETV5 in these lesions is unknown. In this study, we used the KTC1 cell line as a model for human advanced papillary thyroid cancer (PTC) because the cells harbor the heterozygous BRAF (V600E) mutation together with the C250T TERT promoter mutation. The role of ETV5 in PTC proliferation was tested using RNAi followed by high-throughput screening. Signaling pathways driving ETV5 expression were identified using specific pharmacological inhibitors. To determine if ETV5 influences the expression of epithelial-to-mesenchymal (EMT) markers in these cells, an EMT PCR array was used, and data were confirmed by qPCR and ChIP-qPCR. We found that ETV5 is critical for PTC cell growth, is expressed downstream of the MAPK pathway, and directly upregulates the transcription factor TWIST1, a known marker of intravasation and metastasis. Increased ETV5 expression could therefore be considered as a marker for advanced PTCs and a possible future therapeutic target.

Cholangiocarcinoma (CCA) is a biliary malignancy found primarily in adults. The incidence of CCA in children is unknown. The aim of this study was to describe characteristics of CCA in children and adolescents.Using the Surveillance, Epidemiology, and End Results Program (SEER 18) database, we identified incident cases of CCA diagnosed at20 years of age during the period of 1973 to 2013. Additionally, we reviewed published case reports describing pediatric patients with CCA. We calculated descriptive statistics for CCA cases identified in SEER and in case reports. Kaplan-Meier analysis was performed to determine median and 3-year overall survival (OS) rates.We identified 15 children and adolescents diagnosed as having CCA from SEER 18 with an incidence rate of 0.0036 per 100,000. Two-thirds of cases were male, and the majority were white (n = 10). The median age at diagnosis was 17 years (range: 11-19 years). Nine tumors were intrahepatic, 3 extrahepatic, and 3 unspecified. One-third had distal metastases at diagnosis. Eight patients underwent surgical resection including liver transplant in two. Six patients were alive at the time of follow-up. Patients without surgical treatment did not survive. Three-year OS was 50%. Twenty-two children with CCA were found in the literature with a median age at diagnosis of 15 years (range: 3-18 years). Half were male, and 90% had an underlying gastrointestinal comorbidity. Three-year OS was 35.3%.CCA in children and adolescents is rare with poor survival. A high proportion of cases had a history of biliary disease. Surgical resection is necessary for cure.

Background Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy. Procedure RMS cases (n = 322) were enrolled from the third trial coordinated by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 322) were pair matched to cases on race, sex, and age. The following immunizations were assessed: diphtheria, pertussis, and tetanus (DPT); measles, mumps, and rubella; and oral polio vaccine. We also evaluated if immunizations were complete versus incomplete. We examined selected infections including chickenpox, mumps, pneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis, and lung infections. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for maternal education and total annual income. Results Incomplete immunization schedules (OR = 5.30, 95% CI: 2.47–11.33) and incomplete DPT immunization (OR = 1.56, 95% CI: 1.06–2.29) were positively associated with childhood RMS. However, infections did not appear to be associated with childhood RMS. Conclusions This is the largest study of RMS to date demonstrating a possible protective effect of immunizations against the development of childhood RMS. Further studies are needed to validate our findings. Our findings add to the growing body of literature, suggesting a protective role of routine vaccinations in childhood cancer and specifically in childhood RMS.

Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non-Hodgkin lymphoma (NHL) compared to HIV-negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub-Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV-infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV-infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.

Background Due to concerns over the impact of traffic-related air pollution on childhood cancers, we evaluated the association between residential proximity to major roadways and childhood central nervous system (CNS) tumors. Methods The Texas Cancer Registry provided information on children diagnosed with a CNS tumor at 500 m from the nearest major roadway. Moreover, compared to mothers living in areas with low roadway density, those living in areas with high roadway density were 51% (95% CI: 1.1, 2.1) more likely to have offspring with any CNS tumor and 4.2-times (95% CI: 1.2, 14.9) more likely to have offspring with an ependymoma. There were no statistically significant associations observed between continuous distance to major roadways and ependymoma as well as between the proximity measures and the other evaluated CNS tumor phenotypic groups. Conclusions The results of this large population-based study indicate that mothers who live near major roadways or in areas with high roadway density may be more likely to have offspring with a CNS tumor, particularly an ependymoma.

Objectives. We determined the association between maternal neighborhood socioeconomic position (SEP) and the risk of cleft lip with or without cleft palate (CL±P) or cleft palate alone (CP) in offspring. Methods. We obtained information on CL±P (n = 2555) and CP (n = 1112) cases and unaffected controls (n = 14 735) among infants delivered during 1999 to 2008 from the Texas Birth Defects Registry. Neighborhood SEP variables, drawn from the 2000 US Census, included census tract-level poverty, education, unemployment, occupation, housing, and crowding, from which we created a composite neighborhood deprivation index (NDI). We used mixed-effects logistic regression to evaluate neighborhood SEP and oral clefts. Results. Mothers with CL±P-affected offspring were more likely to live in high-NDI (adverse) areas than mothers with unaffected offspring (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.05, 1.37). This association was strongest among Hispanic mothers (OR = 1.32, 95% CI = 1.07, 1.62). No associations were observed with CP. Conclusions. Using data from one of the world’s largest active surveillance birth defects registries, we found that adverse neighborhood SEP is modestly associated with CL±P, especially among Hispanics. These findings may have important implications for health disparities prevention.

The environmental determinants of pediatric embryonal tumors remain unclear. Because of the growing concern over the impact of exposures to traffic-related air pollution on pediatric cancer, we conducted a population-based study evaluating the impact of maternal residential proximity to major roadways on the risk of pediatric embryonal tumors in offspring. We identified children diagnosed with neuroblastoma, Wilms tumor, retinoblastoma, or hepatoblastoma at

In epidemiologic studies of childhood cancer, environmental exposures are often assigned based on either residence at birth or diagnosis without considering the impact of residential mobility. Therefore, we evaluated residential mobility and exposure assignment differences to hazardous air pollutants between birth and diagnosis in children with a central nervous system (CNS) tumor. Children diagnosed with CNS tumors during 1995-2009 (N=1,196) were identified from the Texas Cancer Registry. Census tract-level estimates of 1,3-butadiene and benzene were used to assign quartiles of exposure based on the maternal residence at birth and the child's residence at diagnosis. Overall, 64% of younger (0-4 years) children and 79% of older (5-14 years) children moved between birth and diagnosis. Using mixed-effects ordinal logistic regression, residence at diagnosis compared to birth did not result in a significant change in exposure assignment for younger children; however, older children were more likely to be placed in a lower 1,3-butadiene or benzene exposure quartile based on residence at diagnosis compared to birth (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.45-0.76; OR=0.57, 95% CI=0.44-0.75, respectively). In conclusion, while the majority of children moved between birth and CNS tumor diagnosis, mobility did not significantly impact 1,3-butadiene and benzene exposure assessment in younger children.

Background Due to increasing concerns regarding air pollution and childhood cancer, we conducted a population-based study evaluating the association between traffic-related hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter [DPM]) and the incidence of childhood central nervous system (CNS) tumors. Procedure Information on children diagnosed with a CNS tumor at

Objective To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. Study design Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P Results There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). Conclusions We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.

Background The presence of a congenital anomaly is associated with increased childhood cancer risk, likely due to large effects of Down syndrome and chromosomal anomalies for leukemia. Less is known about associations with presence of non-chromosomal anomalies. Methods Records of children diagnosed with cancer at

Previous assessments of childhood rhabdomyosarcoma have indicated maternal and birth characteristics may be associated with tumor development; however, much work remains to identify novel and confirm suspected risk factors. Our objective was to evaluate the associations between maternal and birth characteristics and childhood rhabdomyosarcoma.This case-control study included 322 cases and 322 pair-matched controls. Cases were enrolled in a trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls were identified using random digit dialing and were individually matched to cases on race, sex, and age. Families of the case and control subjects participated in a telephone interview, which captured information on maternal characteristics (birth control use, number of prenatal visits, anemia, and abnormal bleeding during pregnancy) and birth characteristics [birth weight, preterm birth, and type of delivery (vaginal vs. cesarean)]. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for age, race, sex, household income, and parental education. As the two most common histologic types of rhabdomyosarcoma are embryonal (n = 215) and alveolar (n = 66), we evaluated effect heterogeneity of these exposures.The only characteristic that was associated with childhood rhabdomyosarcoma, and statistically significant, was abnormal vaginal bleeding during pregnancy (OR 1.75, 95% CI 1.12-2.74). Birth control use (OR 1.45, 95% CI 0.96-2.18), anemia during pregnancy (OR 1.27, 95% CI 0.81-1.99), and preterm birth (OR 2.51, 95% CI 0.74-8.49) were positively associated with childhood rhabdomyosarcoma, but were not statistically significant. Low birth weight [adjusted odds ratios (aOR) 4.46, 95% CI 1.41-14.1] and high birth weight (aOR 2.41, 95% CI 1.09-5.35) were strongly associated with alveolar rhabdomyosarcoma. However, these factors did not display significant effect heterogeneity between histologic types (p0.15 for all characteristics).Overall, we found little evidence that these maternal and birth characteristics are strongly associated with childhood rhabdomyosarcoma.

Importance Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. Objectives To identify specific birth defect–childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. Design, Setting, and Participants This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. Exposures Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. Main Outcomes and Measures Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. Results Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjustedP Conclusions and Relevance Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

Acute leukemia is the most common pediatric malignancy. Some studies suggest early-life exposures to air pollution increase risk of childhood leukemia. Therefore, we explored the association between maternal residential proximity to major roadways and risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Information on cases with acute leukemia (n = 2030) was obtained for the period 1995&ndash, 2011 from the Texas Cancer Registry. Birth certificate controls were frequency matched (10:1) on birth year (n = 20,300). Three residential proximity measures were assessed: (1) distance to nearest major roadway, (2) residence within 500 meters of a major roadway, and (3) roadway density. Multivariate logistic regression was used to generate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Mothers who lived &le, 500 meters to a major roadway were not more likely to have a child who developed ALL (OR = 1.03, 95% CI: 0.91&ndash, 1.16) or AML (OR = 0.84, 95% CI: 0.64&ndash, 1.11). Mothers who lived in areas characterized by high roadway density were not more likely to have children who developed ALL (OR = 1.06, 95% CI: 0.93&ndash, 1.20) or AML (OR = 0.83, 95% CI: 0.61&ndash, 1.13). Our results do not support the hypothesis that maternal proximity to major roadways is strongly associated with childhood acute leukemia. Future assessments evaluating the role of early-life exposure to environmental factors on acute leukemia risk should explore novel methods for directly measuring exposures during relevant periods of development.

BACKGROUND Epidemiological knowledge and predictors of melanoma among children and adolescents in multiethnic populations are limited. PROCEDURE Using data from the Texas Cancer Registry (TCR) and the Surveillance, Epidemiology, and End Results (SEER) 13 database, we identified incident melanoma cases diagnosed at 0-20 years old during 1995-2013 in Texas and the United States, respectively. Using negative binomial regression, associations between demographic factors and melanoma incidence rates (IR) were evaluated by calculating incidence rate ratios (IRR) and 95% confidence intervals (CI). Annual percent change in IRs was assessed with joinpoint regression. RESULTS Overall, the melanoma IR was 4.16 (TCR, n = 634) and 4.84 (SEER, n = 1260) per million. Females, adolescents, non-Hispanic (NH) whites, and Hispanics had higher IRs compared with other groups (P

INTRODUCTION Poly-tobacco use is defined as cigarette and other tobacco consumption with either product used daily or nondaily. While concurrent use of different types of tobacco has been documented within the general population, less is known about poly-tobacco use among HIV-positive smokers and its impact on smoking cessation efforts. OBJECTIVE To characterize the profile of poly-tobacco users (PTU) in a sample of HIV-positive smokers participating in a cessation program. METHODS The study sample consisted of 474 HIV-positive smokers enrolled in a 2-group randomized controlled trial of cigarette smoking cessation comparing a cell phone-based intervention to usual care. Prevalence was determined, and risk factors for poly-tobacco use were evaluated using logistic regression. RESULTS In this cohort of HIV-positive cigarette smokers, 21.6% of participants were PTU, with cigars (73.4%) the most common tobacco product consumed. Among PTU, 73.5% used other form(s) of tobacco some days, and 26.5% use them every day. Perceived discrimination and unemployment were significantly associated with poly-tobacco use after adjusting for other demographic, behavioral, and psychosocial factors. Analysis showed that participants in the cell phone group (vs. usual care) were more likely to report 24-hr abstinence, both among monocigarette users (16.6% vs. 6.3%, p < .001) and PTU (18.5% vs. 0%, p < .001). CONCLUSION Poly-tobacco use prevalence among adult HIV-positive smokers was considerably higher than in the general population. Special attention must be placed on concurrent use of cigarettes and cigars among HIV-positive smokers. Because PTU are a unique population less likely to succeed in brief smoking cessation interventions, effective cessation programs are needed.

Background. People living with human immunodeficiency virus (HIV)/AIDS (PLWHA) have a substantially higher prevalence of cigarette smoking compared to the general population. In addition, PLWHA are particularly susceptible to the adverse health effects of smoking. Our primary objective was to design and test the efficacy over 12 months of a smoking cessation intervention targeting PLWHA. Methods. Participants were enrolled from an urban HIV clinic with a multiethnic and economically disadvantaged patient population. Participants received smoking cessation treatment either through usual care (UC) or counseling delivered by a cell phone intervention (CPI). The 7-day point prevalence abstinence was evaluated at 3, 6, and 12 months using logistic regression and generalized linear mixed models. Results. We randomized 474 HIV-positive smokers to either the UC or CPI group. When evaluating the overall treatment effect (7-day abstinence outcomes from 3-, 6-, and 12-month follow-ups), participants in the CPI group were 2.41 times (P = .049) more likely to demonstrate abstinence compared to the UC group. The treatment effect was strongest at the 3-month follow-up (odds ratio = 4.3, P .05). Conclusions. Cell phone–delivered smoking cessation treatment has a positive impact on abstinence rates compared to a usual care approach. Future research should focus on strategies for sustaining the treatment effect in the long term.

Aim: To evaluate patients’ expectations regarding the perceived utility of whole-genome sequencing (WGS). Materials & methods: We used latent class analysis to characterize individuals enrolled in the MedSeq Project based on their perceived utility of WGS. Multinomial logistic regression was used to evaluate associations between participant characteristics and latent classes. Results: Findings characterized participants into one of three perceived utility groups: enthusiasts, who had a high probability of agreement with all utility items (23%); health conscious, who perceived utility in medically related areas (60%) or skeptics, who had a low probability of agreement with utility items (17%). Trust significantly predicted latent class. Conclusion: Understanding differences in perceived utility of WGS may inform strategies for uptake of this technology.

Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy.RMS cases (n = 322) were enrolled from the third trial coordinated by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 322) were pair matched to cases on race, sex, and age. The following immunizations were assessed: diphtheria, pertussis, and tetanus (DPT); measles, mumps, and rubella; and oral polio vaccine. We also evaluated if immunizations were complete versus incomplete. We examined selected infections including chickenpox, mumps, pneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis, and lung infections. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for maternal education and total annual income.Incomplete immunization schedules (OR = 5.30, 95% CI: 2.47-11.33) and incomplete DPT immunization (OR = 1.56, 95% CI: 1.06-2.29) were positively associated with childhood RMS. However, infections did not appear to be associated with childhood RMS.This is the largest study of RMS to date demonstrating a possible protective effect of immunizations against the development of childhood RMS. Further studies are needed to validate our findings. Our findings add to the growing body of literature, suggesting a protective role of routine vaccinations in childhood cancer and specifically in childhood RMS.

As previous studies of obesity in survivors of pediatric acute lymphoblastic leukemia (ALL) have primarily been conducted among non-Hispanic white survivors or children treated on older protocols, our objective was to describe the prevalence and correlates of overweight status among an ethnically diverse population of pediatric ALL survivors, largely treated with more contemporary therapies. We evaluated the overweight/obesity status of pediatric ALL survivors (n=406) followed in the Texas Children's Cancer Center between 2004 and 2014. Survivors were classified as underweight, normal weight, overweight, or obese on the basis of their body mass index at their most current follow-up visit. Our results showed that Hispanic ethnicity (39% of the subjects) was associated with being overweight (adjusted odds ratio=1.88; 95% confidence interval, 1.13-3.14) or obese (adjusted odds ratio=2.84; 95% confidence interval, 1.59-5.06) at follow-up, even after adjusting for cranial radiotherapy (CRT) exposure. Body mass index z-score at diagnosis was also associated with overweight/obesity at follow-up. In addition, there was a statistically significant interaction between younger age at diagnosis and CRT, indicating that younger age at diagnosis was associated with obesity among patients who received CRT. These findings may help identify pediatric ALL patients that are at increased risk of being overweight or obese after treatment.

Purpose: While cancer risk is increased among children with chromosomal birth defects, less is known about associations between specific non-chromosomal structural birth defects and specific childhood cancers. To investigate these, we established a population-based retrospective cohort of >10 million children by pooling statewide registry data from four U.S. states (Texas, Michigan, North Carolina, and Arkansas) for the period 1992-2013. Methods: Individual level data from birth certificates, birth defects registries, and cancer registries were linked in each state; demographic and diagnostic variables were harmonized; and the data were pooled for the overall analysis. We used Cox proportional hazards models to evaluate associations between 60 birth defects and 31 childhood cancers when there were five or more comorbid cases. A hazard ratio (HR) and 95% confidence interval (CI) was calculated for each birth defect-childhood cancer (BD-CC) pairwise combination, adjusted for maternal age, infant sex, and state. The false discovery rate (FDR) was computed via the Benjamini-Hochberg procedure to account for multiple comparisons. Results: We identified 517,548 children with non-chromosomal structural birth defects and 14,774 children with cancer. The risk of any cancer was increased among children with any non-chromosomal structural defect compared to children without any birth defect (HR=2.6, 95% CI 2.4-2.7). Of 2,511 potential BD-CC combinations, we tested 606 where there were ≥5 comorbid cases and identified 496 BD-CC associations with significantly elevated HRs at a 5% FDR. No significant inverse associations were identified for any BD-CC combination. Notably, hepatoblastoma, astrocytoma, ependymoma, and extracranial germ cell tumors were each strongly associated with several birth defects. For example, the risk of hepatoblastoma was increased among children with atrial septal defects (HR=12.5, 95% CI 7.9-19.7) and craniosynostosis (HR=15.4, 95% CI 7.6-31.3). Astrocytoma and ependymoma were associated with central nervous system (CNS) defects (HR=6.7, 95% CI 4.6-9.8 and HR=7.4, 95%CI 3.5-15.7, respectively). Elevated risk of extracranial germ cell tumors was observed among children with CNS defects (HR=22.5, 95% CI 10.9-46.4) and obstructive genitourinary defects (HR=32.4, 95% CI 16.2-64.6). Conclusions: By pooling registry data across four U.S. states, we were able to evaluate specific BD-CC patterns and report several novel associations. Our findings suggest that children with non-chromosomal birth defects have a significantly elevated risk of several childhood cancers. These findings may inform research into the etiologies of childhood cancer, as well as new cancer surveillance protocols for children with non-chromosomal birth defects. This work was supported by the Cancer Prevention Research Institute of Texas. Citation Format: Jeremy M. Schraw, Tania A. Desrosiers, Wendy N. Nembhard, Glenn Copeland, Robert E. Meyer, Austin L. Brown, Tiffany M. Chambers, Heather E. Danysh, Saumya Sisoudiya, Chunqiao Luo, Amir Mian, Michael E. Scheurer, Sharon E. Plon, Philip J. Lupo. A population-based assessment of cancer risk among children with non-chromosomal birth defects in 10 million live births [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-161.

There is warranted interest in assessing the association between residential radon exposure and the risk of childhood cancer. We sought to evaluate the association between residential radon exposure and the incidence of childhood lymphoma in Texas. The Texas Cancer Registry (n = 2147) provided case information for the period 1995–2011. Denominator data were obtained from the United States Census. Regional arithmetic mean radon concentrations were obtained from the Texas Indoor Radon Survey and linked to residence at diagnosis. Exposure was assessed categorically: ≤25th percentile (reference), &gt, 25th to ≤50th percentile, &gt, 50th to ≤75th percentile, and &gt, 75th percentile. Negative binomial regression generated adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI). We evaluated lymphoma overall and by subtype: Hodgkin (HL, n = 1248), Non-Hodgkin excluding Burkitt (non-BL NHL, n = 658), Burkitt (BL, n = 241), and Diffuse Large B-cell (DLBCL, n = 315). There was no evidence that residential radon exposure was positively associated with lymphoma overall, HL, or BL. Areas with radon concentrations &gt, 75th percentile had a marginal increase in DLBCL incidence (aIRR = 1.73, 95% CI: 1.03–2.91). In one of the largest studies of residential radon exposure and the incidence of childhood lymphoma, we found little evidence to suggest a positive or negative association, an observation consistent with previous studies.

Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case-control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Children's Oncology Group (COG). Population-based controls (n = 322) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (OR(s) ) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (OR(s) = 1.39, 95% CI: 0.97-1.98). Notably, this association was stronger among those with embryonal RMS (OR(s) = 2.44, 95% CI: 1.54-3.86). Moreover, having a first-degree relative who was younger at diagnosis of cancer (30 years) was associated with a greater risk of RMS (OR(s) = 2.37, 95% CI: 1.34-4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first-degree relative with cancer, and among those whose relatives were diagnosed with cancer at30 years of age.

El Nino is responsible for natural disasters and infectious disease outbreaks worldwide. During the 1997–1998 El Nino, northern Peru endured extreme rainfall and flooding. Since short stature may occur as a result of undernutrition or repeated infections during childhood, both of which are highly prevalent during natural disasters, we sought to determine if the 1997–1998 El Nino had an adverse effect on stature and body composition a decade later. In 2008–2009, we measured height, weight, and bioimpedance in a random sample of 2,095 children born between 1991 and 2001 in Tumbes, Peru. Height-for-age increased by 0.09 SD/year of birth between 1991 and 1997 (P

Due to increasing concerns regarding air pollution and childhood cancer, we conducted a population-based study evaluating the association between traffic-related hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter [DPM]) and the incidence of childhood central nervous system (CNS) tumors.Information on children diagnosed with a CNS tumor at15 years of age, in Texas, for the period of 2001-2009 (n = 1,949) was obtained from the Texas Cancer Registry. Information on the corresponding at-risk population was obtained from the United States (U.S.) Census. Annual census tract-level pollutant concentrations, estimated by the U.S. Environmental Protection Agency, were categorized based on quartiles (low, medium, medium-high, and high) of the statewide distribution. Multivariable Poisson regression was used to calculate adjusted incidence rate ratios (aIRR). Juvenile pilocytic astrocytomas (JPAs) (n = 384), other astrocytomas (n = 372), ependymomas (n = 142), medulloblastomas (n = 235), and primitive neuroectodermal tumors (PNET) (n = 47) were evaluated.Census tracts with medium and medium-high 1,3-butadiene concentrations had higher astrocytoma incidence rates (aIRR [95% confidence interval (CI)]: 1.46 [1.05-2.01] and 1.69 [1.22-2.33], respectively) compared with low concentrations. Census tracts with medium DPM concentrations had higher astrocytoma (aIRR [95%CI]: 1.42 [1.05-1.94]) and medulloblastoma (aIRR [95%CI]: 1.46 [1.01-2.12]) incidence rates compared with low concentrations. Increased concentrations of 1,3-butadiene and benzene were strongly associated with increased PNET incidence rates, but were not statistically significant. No associations were detected with JPA or ependymoma incidence.In one of the largest studies of its kind, our results suggest positive associations between hazardous air pollutants and incidence of astrocytoma (1,3-butadiene and DPM) and medulloblastoma (DPM).

Background While there is evidence that maternal exposure to benzene is associated with spina bifida in offspring, to our knowledge there have been no assessments to evaluate the role of multiple hazardous air pollutants (HAPs) simultaneously on the risk of this relatively common birth defect. In the current study, we evaluated the association between maternal exposure to HAPs identified by the United States Environmental Protection Agency (U.S. EPA) and spina bifida in offspring using hierarchical Bayesian modeling that includes Stochastic Search Variable Selection (SSVS). Methods The Texas Birth Defects Registry provided data on spina bifida cases delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual HAP levels were obtained from the U.S. EPA’s 1999 Assessment System for Population Exposure Nationwide. Using the distribution among controls, exposure was categorized as high exposure (>95th percentile), medium exposure (5th-95th percentile), and low exposure ( 0.80). We identified two out of 25 HAPs with a Bayes factor greater than 1: quinoline (ORhigh = 2.06, 95% CI: 1.11-3.87, Bayes factor = 1.01) and trichloroethylene (ORmedium = 2.00, 95% CI: 1.14-3.61, Bayes factor = 3.79). Conclusions Overall there is evidence that quinoline and trichloroethylene may be significant contributors to the risk of spina bifida. Additionally, the use of Bayesian hierarchical models with SSVS is an alternative approach in the evaluation of multiple environmental pollutants on disease risk. This approach can be easily extended to environmental exposures, where novel approaches are needed in the context of multi-pollutant modeling. Electronic supplementary material The online version of this article (doi:10.1186/1476-069X-14-16) contains supplementary material, which is available to authorized users.

HIV-positive women are at elevated risk for developing cervical cancer. While emerging research suggests that gynecologic health care is underutilized by HIV-positive women, factors associated with adherence to Pap testing, especially among HIV-positive female smokers are not well known. We utilized baseline data from a smoking cessation trial and electronic medical records to assess Pap smear screening prevalence and the associated characteristics among the HIV-positive female participants (n=138). Forty-six percent of the women had at least 1 Pap test in the year following study enrollment. Multiple logistic regression analysis indicated that younger age, African American race, hazardous drinking, increased number of cigarettes smoked per day, and smoking risk perception were associated with non-adherence to Pap smear screening. Cervical cancer screening was severely underutilized by women in this study. Findings underscore the importance of identifying predictors of non-adherence and addressing multiple risk factors and behavioral patterns among HIV-positive women who smoke.

During the 1997-98 El Nino, Tumbes, Peru received 16 times the annual average rainfall. This study explores how Tumbes residents perceived the impact of the El Nino event on basic necessities, transport, health care, jobs and migration. Forty-five individuals from five rural communities, some of which were isolated from the rest of Tumbes during the event, participated in five focus groups; six of these individuals constructed nutrition diaries. When asked about events in the past 20 years, participants identified the 1997-98 El Nino as a major negative event. The El Nino disaster situation induced a decrease in access to transport and health care and the rise in infectious diseases was swiftly contained. Residents needed more time to rebuild housing; recover agriculture, livestock and income stability; and return to eating sufficient animal protein. Although large-scale assistance minimized effects of the disaster, residents needed more support. Residents' perspectives on their risk of flooding should be considered in generating effective assistance policies and programmes.

Background Lymphoma is one of the most common pediatric malignancies; however, there are few well-established risk factors. Therefore, we investigated if maternal and perinatal characteristics influenced the risk of childhood lymphoma. Procedure Information on cases (n = 374) diagnosed with lymphoma and born in Texas for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were randomly selected at a ratio of 10 controls per 1 case for the same period of 1995-2011. Unconditional logistic regression was used to generate unadjusted (OR) and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the following histologic subtypes: Hodgkin (HL), Burkitt (BL), and non-BL non-HLs (non-BL NHLs). Results Overall, our findings indicate specific maternal and perinatal characteristics influence childhood lymphoma risk. Mexico-born mothers were more likely to have offspring who developed BL compared to mothers born in the United States (U.S.; aOR: 2.15; 95% CI: 1.06-4.36). Further, mothers who resided at time of delivery in a county on the U.S.-Mexico border were more likely to give birth to offspring who developed non-BL NHL (aOR: 1.72; 95% CI: 1.11-2.67) compared to mothers not living on the U.S.-Mexico border at time of infant birth. Last, infants born large-for-gestational-age experienced a twofold increase in BL risk (aOR: 2.00; 95% CI: 1.10-3.65). Conclusions In this population-based assessment, we confirmed previously reported risk predictors of childhood lymphoma, including sex of infant, while highlighting novel risk factors that warrant assessment in future studies.

Purpose: In the United States, lymphoma represents approximately one-third of all malignancies in those less than 20 years of age. As most cases are of unknown etiology, the identification of risk factors for the prevention of childhood lymphoma is critical. Parental and birth characteristics are often evaluated in studies of childhood cancer to determine the role of inborn variation on disease risk. Thus we sought to evaluate the role of parental and birth characteristics on the risk of childhood lymphoma. Material and Methods: Cases (n = 374) were obtained from the Texas Cancer Registry (TCR) and limited to children born in Texas during or after 1995 and diagnosed with a lymphoma between 1995-2011. Diagnostic information came from the TCR, and case birth characteristic data was obtained from linked Texas birth certificates provided by the Center for Health Statistics. A randomly selected group of 10 controls for each case with subsequent birth characteristic data available was obtained from linked birth certificates. Multinomial logistic regression was used to generate relative-risk ratios (aRRR) and 95% confidence intervals (CI), adjusted for relevant covariates, to evaluate the association between several parental and birth characteristics and lymphoma risk (overall and by subtype). Results: Most parental and birth characteristics were not associated with risk of childhood lymphoma. However, two factors were associated with lymphoma risk overall and by subtype: maternal race/ethnicity and infant sex. When compared to non-Hispanic white mothers, Hispanic mothers were more likely to have offspring that developed: 1) any lymphoma (aRRR: 1.09; 95% CI: 0.85-1.40) and 2) non-Hodgkin excluding Burkitt lymphoma (aRRR: 1.42; 95% CI: 0.96-2.11). The reverse was seen for non-Hispanic black mothers. There was also a disparity in risk by infant sex. Specifically, female children were at a decreased risk of developing all lymphomas (aRRR: 0.59; 95% CI: 0.47-0.74); Hodgkin lymphoma (aRRR: 0.65; 95% CI: 0.46-0.92); and Burkitt lymphoma (aRRR: 0.18; 95% CI: 0.10-0.33) when compared to male children. Additionally, paternal nativity was suggested to increase overall lymphoma risk (aRRR: 1.29; 95% CI: 0.96-1.73); an increase specifically suggested among those diagnosed with Hodgkin lymphoma (aRRR: 1.46; 95% CI: 0.93-2.32). Conclusion: In this relatively large population-based study of these factors on the risk of childhood lymphoma, we found little evidence that parental and birth characteristics were strongly associated with disease risk. Citation Format: Erin C. Peckham, Michael E. Scheurer, Heather E. Danysh, Austin L. Brown, Joseph Lubega, Philip J. Lupo. Parental and birth characteristics and childhood lymphoma in Texas, 1995-2011. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5215.

Adherence to antiretroviral therapy (ART) has markedly improved HIV disease management, and significantly reduced HIV/AIDS-associated morbidity and mortality. Although recent studies suggest a relationship between smoking and suboptimal adherence to ART, a more in-depth understanding of this relationship is needed. We conducted a secondary analysis using data from a randomized controlled smoking cessation trial to investigate the association of nonadherence to ART with potential demographic, psychosocial (perceived stress and depression), and substance use (nicotine dependence, illicit drug use, and alcohol use) variables among persons living with HIV/AIDS (PLWHA) who smoke. The mean (standard deviation [SD]) age of participants (n=326) was 45.9 years old (SD=7.6). Additionally, the majority were male (72.1%), self-identified as black (76.7%), and reported sexual contact as the mode of HIV acquisition (70%). Unadjusted logistic regression analysis indicated that depression (odds ratio [OR]=1.02; 95% confidence interval [CI]=1.00, 1.04), illicit drug use (OR=2.39; 95% CI=1.51, 3.79) and alcohol use (OR=2.86; 95%CI=1.79, 4.57) were associated with nonadherence. Adjusted logistic regression analysis indicated that nicotine dependence (OR=1.13; 95% CI=1.02, 1.25), illicit drug use (OR=2.10; 95% CI=1.27, 3.49), alcohol use (OR=2.50; 95% CI=1.52, 4.12), and age (OR=1.04; 95% CI=1.00, 1.07) were associated with nonadherence. Nicotine dependence, illicit drug use, and alcohol use are potentially formidable barriers to ART adherence among PLWHA who smoke. Future efforts should investigate the complex relationships among these variables to improve adherence particularly among populations confronted with multifaceted health challenges.

Background: Rhabdomyosarcoma (RMS) is a rare, highly malignant childhood cancer with an annual incidence of four cases per million and approximately 350 new cases are diagnosed in the U.S. annually. Due to its rarity, relatively little is known about the etiology of this childhood malignancy. Early immunologic challenges such as immunizations and infections have been hypothesized to be protective in certain malignancies. To our knowledge, these associations have not been studied in relation to childhood RMS risk. The purpose of our study was to better characterize the association between childhood immunizations and infections and RMS risk using data from the largest case-control study of RMS to date. Materials and Methods: Cases (n = 322) were previously enrolled in the Intergroup Rhabdomyosarcoma Study, which became a part of the Children's Oncology Group in 2000. Controls (n = 322) were selected by random-digit telephone dialing and pair-matched to cases on race, sex, and age. We evaluated RMS risk based on whether parents reported that their child was up-to-date on immunizations and had completed their DPT (diphtheria, pertussis and tetanus), oral polio, and MMR (measles, mumps and rubella) series. In addition, we evaluated whether the child ever had previous infections including mumps, pneumonia, rubella, rubeola, pertussis, tuberculosis, meningitis, scarlet fever, and chickenpox. Conditional logistic regression models were used to calculate an adjusted odds ratio (aOR) and 95% confidence interval (CI) for each exposure, adjusted for age, race, and sex. Results: Having up-to-date immunizations had a protective effect on childhood RMS (aOR = 0.22, 95% CI: 0.11-0.44). More specifically, children who did not receive the complete vaccination series of DPT (aOR = 1.70 95% CI: 1.18-2.50) or did not receive the MMR vaccine (aOR = 1.59, 95% CI: 1.04-2.44) had an increased risk of being diagnosed with childhood RMS. Most infectious conditions examined were negatively associated with childhood RMS; however, these findings were not statistically significant (p>0.05). Conclusions: This is the first study of its kind to provide evidence that receiving childhood immunizations may be protective against RMS risk. Although the effect estimates suggested a possible protective role of childhood infections against RMS risk, these findings were not statistically significant. Future studies will be needed to further evaluate the role of immunizations and childhood infections in the development of this tumor. Citation Format: Hari Sankaran, Heather Danysh, Michael E. Scheurer, M. Fatih Okcu, Philip J. Lupo. The role of childhood immunizations and infections on the risk of pediatric rhabdomyosarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 845. doi:10.1158/1538-7445.AM2015-845

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. In the United States, about 350 children are diagnosed with RMS per year. The two major histologic subtypes of RMS are embryonal (ERMS; approximately 70% of cases) and alveolar (ARMS; approximately 30% of cases). A small percentage of RMS cases are associated with germline mutations in TP53, HRAS, and NF1. However, it has been difficult to show if inherited susceptibility may play a role in sporadic cases due to the rarity of these tumors and the potential etiologic heterogeneity between subtypes. Objective: In order to better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case-control study of RMS to date. Methods: Cases (n=322) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n=322) were pair matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate cancer history among first- and second-degree relatives and the association with childhood RMS by generating adjusted odds ratios (aOR) and 95% confidence intervals (CI). Stratified analyses were conducted to independently evaluate the association of family cancer history and childhood RMS for children who had relatives diagnosed with a cancer before the age of 40 years and those with relatives diagnosed when older than 40 years. The association of family cancer history and childhood RMS was also assessed separately for children diagnosed with ERMS and those diagnosed with ARMS. Results: While there were no statistically significant associations, three patterns appeared to emerge: 1) having any first degree relative with a history of cancer was more common in RMS cases than controls (aOR=1.46, 95% CI: 0.72-2.97); 2) having a first degree relative who was younger at diagnosis ( Conclusions: In the largest analysis of its kind to date, we found that family history of cancer appeared to increase the risk of childhood RMS. While the associations were not statistically significant, this is likely due to the low prevalence of family cancer history in this population (i.e., 6.6% overall). Ultimately, these findings tentatively support the role of inherited genetic susceptibility in the development of childhood RMS. Citation Format: Philip J. Lupo, Heather E. Danysh, Sharon E. Plon, David Malkin, Simone Hettmer, Douglas S. Hawkins, Stephen X. Skapek, Logan G. Spector, Karin Papworth, Beatrice Melin, Erik B. Erhardt, Seymour Grufferman. Family history of cancer and rhabdomyosarcoma in children: a report from the Children's Oncology Group. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1296. doi:10.1158/1538-7445.AM2014-1296

Background: Human papillomavirus (HPV) infection is a necessary cause in the development of cervical cancer; however, not all women infected with HPV develop cervical cancer indicating that other risk factors are involved. Our objective was to determine the association between exposure to ambient levels of common traffic-related air toxics and cervical dysplasia, a precursor lesion for cervical cancer. Methods: The study sample consisted of women enrolled in a Phase II clinical trial to evaluate diagnostic techniques for cervical disease in Houston, Texas. The current assessment is a secondary data analysis in which cases were defined as women diagnosed with cervical dysplasia, while those without cervical dysplasia served as controls. Residential census tract-level estimates of ambient benzene, diesel particulate matter (DPM), and polycyclic aromatic hydrocarbons (PAHs) were used to assess exposure. Census tract-level pollutant estimates were obtained from the United States Environmental Protection Agency. Multivariable logistic regression was used to estimate prevalence odds ratios (aOR) and 95% confidence intervals (CI) adjusted for age, race/ethnicity, education, smoking status, and HPV status. Results: Women in the highest residential exposure categories for benzene and DPM had an increased prevalence of cervical dysplasia compared to the lowest exposure category (Benzene: aOR [95% CI] for high exposure = 1.97 [1.07-3.62], very high exposure = 2.30[1.19-4.46]. DPM: aOR [95% CI] for high exposure = 2.83[1.55-5.16], very high exposure = 2.10[1.07-4.11]). Similarly, women with high residential exposure to PAHs had an increased prevalence of cervical dysplasia (aOR [95% CI] = 2.46[1.35-4.48]). The highest PAH exposure category was also positively associated with cervical dysplasia prevalence but was not statistically significant. Assessment of the combined effect of HAP exposure indicates that exposure to high levels of more than one HAP is positively associated with cervical dysplasia prevalence (p for trend=0.004). Conclusions: Traffic-related HAPs, such as benzene, DPM, and PAHs, are not as well-regulated and monitored as criteria air pollutants (e.g., ozone), underscoring the need for studies evaluating the role of these toxicants on disease risk. Our results suggest that exposure to traffic-related air toxics may increase cervical dysplasia prevalence.

Background Despite a significant decrease in smoking prevalence over the past ten years, cigarette smoking still represents the leading cause of preventable morbidity and mortality in the United States. Moreover, smoking prevalence is significantly higher among those with low levels of education and those living at, or below, the poverty level. These groups tend to be confronted with significant barriers to utilizing more traditional smoking cessation intervention approaches. The purpose of the study, Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods), is to utilize a mobile clinic model, a network of community sites (i.e., community centers and churches) and an interactive mobile messaging system to reach and deliver smoking cessation treatment to underserved, low-income communities. Methods/Design We are using a group-randomized design, with the community site as the sampling unit, to compare the efficacy of three smoking cessation interventions: 1) Standard Care - brief advice to quit smoking, nicotine replacement therapy (NRT), and self-help materials; 2) Enhanced Care - standard care components plus a cell phone-delivered text/graphical messaging component; and 3) Intensive Care - enhanced care components plus a series of 11 cell phone-delivered proactive counseling sessions. An economic evaluation will also be performed to evaluate the relative cost effectiveness of the three treatment approaches. We will recruit 756 participants (252 participants in each of the 3 intervention groups). At the time of randomization, participants complete a baseline assessment, consisting of smoking history, socio-demographic, and psychosocial variables. Monthly cell phone assessments are conducted for 6 months-post enrollment, and a final 12-month follow-up is conducted at the original neighborhood site of enrollment. We will perform mixed-model logistic regression to compare the efficacy of the three smoking cessation intervention treatment groups. Discussion It is hypothesized that the intensive care approach will most successfully address the needs of the target population and result in the highest smoking cessation rates. In addition to increasing cessation rates, the intervention offers several features (including neighborhood outreach and use of mHealth technology) that are likely to reduce treatment barriers while enhancing participant engagement and retention to treatment. Trial registration This randomized controlled trial is registered with clinicaltrials.gov registration number NCT00948129.