a report from the Children's Oncology Group and the Utah Population Database

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 (ORs) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (ORs = 1.39, 95% CI: 0.97–1.98). Notably, this association was stronger among those with embryonal RMS (ORs = 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 (ORs = 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 at <30 years of age

MODEL PENGELOLAAN PASCA TANGKAP SEBAGAI UPAYA PENGENTASAN KEMISKINAN MASYARAKAT KAMPUNG NELAYAN DI PULAU ENGGANO

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 (ORs) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (ORs=1.39, 95% CI: 0.97-1.98). Notably, this association was stronger among those with embryonal RMS (ORs=2.44, 95% CI: 1.54-3.86). Moreover, having a first-degree relative who was younger at diagnosis of cancer (&lt;30years) was associated with a greater risk of RMS (ORs=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 at &lt;30years of age

Traffic-related air pollution exposure and childhood central nervous system tumors

There is a growing concern over the impact of exposure to traffic-related air pollutants and childhood central nervous system (CNS) tumors. The objective of this project was to assess exposure to high levels of traffic-related air pollution as a risk factor for childhood CNS tumors overall, as well as the specific CNS tumor histologic types (e.g., astrocytoma and medulloblastoma). In addition, we assessed the impact of residential mobility of CNS tumor cases between birth and diagnosis on air pollution exposure assessment. Data from the Texas Cancer Registry were used to: 1) conduct an ecologic study assessing the associations between area-level concentrations of traffic-related hazardous air pollutants (HAP) and the incidence of CNS tumors in children \u3c 15 years of age; 2) conduct a case-control study assessing maternal residential proximity to major roadways at delivery and risk of having offspring who develop a CNS tumor at \u3c 5 years of age; and 3) assess the extent to which change of residence may result is differential HAP exposure classification when based on maternal residence at birth compared to when based on the child\u27s residence at diagnosis. We found that census tracts with medium and medium-high 1,3-butadiene concentrations had higher astrocytoma incidence rates (IRR [95% CI]: 1.5 [1.1, 2.0] and 1.7 [1.2, 2.3], respectively) compared with census tracts with low concentrations. Census tracts with medium diesel particulate matter concentrations had higher astrocytoma (IRR [95% CI]: 1.4 [1.1, 1.9]) and medulloblastoma (IRR [95% CI]: 1.5 [1.0, 2.1]) incidence rates compared with census tracts with low concentrations. Furthermore, mothers who lived in areas with high roadway density were 1.5-times more likely (95% CI: 1.1, 2.1) and 4.2-times more likely (95% CI: 1.2, 14.9) to have offspring with any CNS tumor and an ependymoma, respectively, when compared to mothers living in areas with low roadway density. On the question of differential exposure classification based on residential mobility, we found that HAP exposures assessed using the child\u27s residence at diagnosis may be a reasonable proxy for exposures at birth for tumors diagnosed in early childhood (0-4 years old) (p = 0.277). In contrast, HAP exposure at birth may not be an accurate measure of HAP exposure at diagnosis, and vice versa, for tumors diagnosed in older children (5-14 years old) (p \u3c 0.001). This project is the first to report statistically significant associations between exposure to traffic-related air pollutants and astrocytoma, ependymoma, and medulloblastoma in children. Our results contribute to the growing body of evidence regarding air pollutant exposure and childhood cancers

Maternal Residential Proximity to Major Roadways and Pediatric Embryonal Tumors in Offspring

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 &lt;5 years of age from the Texas Cancer Registry and selected unaffected controls from birth certificates. Two residential proximity measures were used: (1) distance to the nearest major roadway, and (2) within 500 m of a major roadway. Logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for each proximity measure on pediatric embryonal tumors. The odds of an embryonal tumor were increased in children born to mothers living within 500 m of a major roadway (aOR = 1.24, 95% CI: 1.00, 1.54). This was consistent for most tumor subtypes, with the strongest associations observed for unilateral retinoblastoma (aOR = 2.57, 95% CI: 1.28, 5.15, for every kilometer closer the mother lived to the nearest major roadway). These findings contribute to the growing evidence that traffic-related air pollution may increase risk for certain pediatric tumors

Residential Radon Exposure and Incidence of Childhood Lymphoma in Texas, 1995–2011

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

The Transcription Factor ETV5 Mediates BRAFV600E-Induced Proliferation and TWIST1 Expression in Papillary Thyroid Cancer Cells

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