There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children < age 6, and 19,209 controls from California birth records within 2km (1.3 miles) (ALL) and 6km (3.8 miles) (AML) of an air toxics monitoring station between 1990–2007. Information on air toxics exposures was taken from community air monitors. We used logistic regression to estimate the risk of leukemia associated with one interquartile range increase in air toxic exposure. Risk of ALL was elevated with 3rd trimester exposure to polycyclic aromatic hydrocarbons (OR=1.16, 95%CI 1.04, 1.29), arsenic (OR=1.33, 95%CI 1.02, 1.73), benzene (OR=1.50, 95%CI 1.08, 2.09), and three other toxics related to fuel combustion. Risk of AML was increased with 3rd trimester exposure to chloroform (OR=1.30, 95%CI 1.00, 1.69), benzene (1.75, 95%CI 1.04, 2.93), and two other traffic-related toxics. During the child’s first year, exposure to butadiene, ortho-xylene, and toluene increased risk for AML and exposure to selenium increased risk for ALL. Benzene is an established cause of leukemia in adults; this study supports that ambient exposures to this and other chemicals in pregnancy and early life may also increase leukemia risk in children.
Childhood leukemia; pregnancy; polycyclic aromatic hydrocarbons; benzene; toluene; lead; chloroform; xylenes; arsenic; childhood cancer epidemiology
Epidemiologic studies indicate that infections in early childhood may protect against pediatric acute lymphoblastic leukemia (ALL).
We identified 3,402 ALL cases among children 0–5 years using the California Cancer Registry. From California birth records we randomly selected controls in a 20:1 ratio and frequency matched them to cases by birth year. We investigated markers of exposure to infections, including month of birth, timing of birth in relation to influenza and respiratory syncytial virus (RSV) seasons, and birth order based on data from California birth certificates and national infection surveillance systems.
We observed an increased risk of ALL for spring and summer births, and for those first exposed to an influenza or RSV season at nine to twelve months of age compared to those exposed during the first three months of life, and this association was stronger among first born children (OR and 95% CI 1.44 [1.13, 1.82] for influenza exposure at nine to twelve months of age). Decreased risk was observed with increasing birth order among non-Hispanic whites but not Hispanics (OR and 95% CI 0.76 [0.59, 096] for fourth or higher birth order among whites).
Our results support the hypothesis that infections in early childhood decrease risk of ALL.
Our findings implicate early life exposure to infections as protective factors for ALL in young children.
Children; Epidemiology; Infant; Influenza; Human; Leukemia; Lymphoid; Respiratory Syncytial Virus
To study prenatal air toxics exposure and Wilms’ tumor in children.
We identified 337 Wilms’ tumor cases among children <6 years (1988-2008) from the California Cancer Registry, randomly selected 96,514 controls from California birth rolls in 20:1 ratio matched to all cancer cases, then linked birth addresses to air monitors within 15 miles to assess exposures. Multiple logistic regressions were applied to estimate effects.
Children prenatally exposed to formaldehyde, polycyclic aromatic hydrocarbons, perchloroethylene, or acetaldehyde in the third trimester had an increased odds of Wilms’ tumor per interquartile increase in concentration (OR [95%CI]: 1.28 [1.12, 1.45], 1.10 [0.99, 1.22], 1.09 [1.00, 1.18], 1.25 [1.07, 1.45] respectively).
We found positive associations for four air toxics. This is the first study of this kind. Future studies are needed to confirm our findings.
The relationship between neighborhood/individual characteristics and pediatric intensive care unit (PICU) outcomes is largely unexplored. We hypothesized that individual- level racial/ethnic minority status and neighborhood-level low socioeconomic status and minority concentration would adversely affect children’s severity of illness on admission to the PICU. Retrospective analyses (1/1/2007–5/ 23/2011) of clinical, geographic, and demographic data were conducted at an academic, tertiary children’s hospital PICU. Clinical data included age, diagnosis, insurance, race/ethnicity, Pediatric Index of Mortality 2 score on presentation to the PICU (PIM2), and mortality. Residential addresses were geocoded and linked with 2010 US Census tract data using geographic information systems geocoding techniques. Repeated measures models to predict PIM2 and mortality were constructed using three successive models with theorized covariates including the patient’s race/ethnicity, the predominant neighborhood racial/ethnic group, interactions between patient race/ethnicity and neighborhood race/ethnicity, neighborhood socioeconomic status, and insurance type. Of the 5,390 children, 57.8 %were Latino and 70.1 %possessed government insurance. Latino children (β = 0.31; p < 0.01), especially Latino children living in a Latino ethnic enclave (β = 1.13; p < 0.05), had higher PIM2 scores compared with non-Latinos. Children with government insurance (β = 0.29; p < 0.01) had higher PIM2 scores compared to children with other payment types and median neighborhood income was inversely associated with PIM2 scores (β = −0.04 per $10,000/year of income; p < 0.05). Lower median neighborhood income, Latino ethnicity, Latino children living in a predominantly Latino neighborhood, and children possessing government insurance were associated with a higher severity of illness on PICU admission. The reasons why these factors affect critical illness severity require further exploration.
Neighborhood; Geocoding; Pediatric; Intensive care; Health care disparities
Research is limited on the independent and joint effects of individual- and neighborhood-level socioeconomic status (SES) on breast cancer survival across different racial/ethnic groups.
We studied individual-level SES, measured by self-reported education, and a composite neighborhood SES (nSES) measure in females (1,068 non-Hispanic whites, 1,670 Hispanics, 993 African-Americans, and 674 Asian-Americans), aged 18–79 years and diagnosed 1995–2008, in the San Francisco Bay Area. We evaluated all-cause and breast cancer-specific survival using stage-stratified Cox proportional hazards models with cluster adjustment for census block groups.
In models adjusting for education and nSES, lower nSES was associated with worse all-cause survival among African-Americans (p-trend=0.03), Hispanics (p-trend=0.01) and Asian-Americans (p-trend=0.01). Education was not associated with all-cause survival. For breast cancer-specific survival, lower nSES was associated with poorer survival only among Asian-Americans (p-trend=0.01). When nSES and education were jointly considered, women with low education and low nSES had 1.4 to 2.7-times worse all-cause survival than women with high education and high nSES across all races/ethnicities. Among African-Americans and Asian-Americans, women with high education and low nSES had 1.6 to 1.9-times worse survival, respectively. For breast cancer-specific survival, joint associations were found only among Asian-Americans with worse survival for those with low nSES regardless of education.
Both neighborhood and individual SES are associated with survival after breast cancer diagnosis, but these relationships vary by race/ethnicity.
A better understanding of the relative contributions and interactions of SES with other factors will inform targeted interventions towards reducing long-standing disparities in breast cancer survival.
breast cancer survival; neighborhood socioeconomic status; education; race/ethnicity
There is a general consensus that pesticides are involved in the etiology of Parkinson’s disease (PD), although associations between specific pesticides and the risk of developing Parkinson’s disease have not been well studied. This study examines the risk of developing PD associated with specific organophosphate pesticides and their mechanisms of toxicity.
This case-control study uses a geographic information system (GIS)-based exposure assessment tool to estimate ambient exposure to 36 commonly used organophosphates (OPs) from 1974-1999. All selected OPs were analyzed individually and also in groups formed according to their presumed mechanisms of toxicity.
The study included 357 incident PD cases and 752 population controls living in the Central Valley of California. Ambient exposure to each OP evaluated separately increased the risk of developing PD. However, most participants were exposed to combinations of OPs rather than a single pesticide. Risk estimates for OPs grouped according to different presumed functionalities and toxicities were similar and did not allow us to distinguish between them. However, we observed exposure-response patterns with exposure to an increasing number of OPs.
This study adds strong evidence that OPs are implicated in the etiology of idiopathic PD. However, studies of OPs at low doses reflective of real-world ambient exposure are needed to determine the mechanisms of neurotoxicity.
To identify and test mediators of the relationship between acculturation and sun-safe behaviors among Latinos in the United States. We hypothesized that the effect of acculturation on use of sunscreen, shade, and sun-protective clothing would be mediated by perceived health status, educational level, access to healthcare, and contact with social networks regarding health matters.
The 2005 Health Information National Trends Survey, implemented by the National Cancer Institute.
A probability-based sample of the US civilian, noninstitutionalized adult population, comprising 496 Latino respondents.
Main outcome measures
Use of sunscreen, shade, and sun-protective clothing when outdoors on sunny days, assessed by self-reports on frequency scales.
The positive association between acculturation and sunscreen use and the negative association between acculturation and use of sun-protective clothing were mediated by educational level (P<0.05 for both). Perceived health status and contact with social networks regarding health matters were supported as mediators only for sunscreen use (P<0.05). Health care access was not supported as a mediator for any of the outcomes.
Structural equation models revealed distinct direct and indirect paths between acculturation and each sun-safe practice. Our findings place an emphasis on behavior-specific mediated associations and could inform sun safety programming for Latinos with low and high levels of acculturation. The models support education level, contact with social networks regarding health matters, and perceived health status as mediators primarily for sunscreen use. Future research should test different mediators for use of shade or sun-protective clothing.
Human immunodeficiency virus (HIV) infection substantially elevates diffuse large B-cell lymphoma (DLBCL) risk, but its impact on the distinct DLBCL subtypes defined by cell of origin is unclear. We compared DLBCL molecular characteristics and prognosis in 51 HIV-infected and 116 HIV-uninfected cases diagnosed during 1977-2003. Using immunohistochemistry to classify cell of origin based on the Tally algorithm, activated B-cell (ABC)-DLBCL was substantially more common in HIV-infected (83%) than in HIV-uninfected (54%) cases (p< 0.001). Epstein-Barr virus (EBV) was detected in 63% of DLBCLs in HIV-infected cases, occurring almost exclusively in ABC-DLBCL (74% vs. 13% of germinal center B-cell [GCB]-DLBCL, p=0.002), but was rarely detected in DLBCLs among HIV-uninfected cases (3%). Among HIV-uninfected cases, MYC/IgH[t(8;14)(q24;q32)] and IgH/BCL2[t(14;18)(q32;q21)] translocations were significantly more common and BCL6/IgH[t(3;14)(q27;q32)] significantly less common in GCB-DLBCL than in ABC-DLBCL (p= 0.010, < 0.001 and = 0.039, respectively). Among HIV-infected cases, translocations other than MYC/IgH[t(8;14)(q24;q32)] (21%) were rare (≤6%) and unrelated to cell of origin. ABC-DLBCL was associated with adverse overall survival compared with GCB-DLBCL regardless of HIV status (pHIV-infected= 0.066;pHIV-uninfected= 0.038). Our data demonstrate key differences in the molecular characteristics, cell of origin and prognosis of DLBCL by HIV status in the pre-highly active antiretroviral therapy (HAART) and pre-rituximab era, supporting biologic differences in lymphomagenesis in the presence of HIV.
Diffuse large B-cell lymphoma; Epstein-Barr virus; activated B-cell; germinal center B-cell
Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored.
Design and methods
BL tissues from residual tissue repositories, and 2 academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV early RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student’s t-test.
Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age-group 0-19 to 55% in age-group 20-34, and fell to 25% in age-group 60+ years, P=0.08); with race (56% in Blacks/Hispanics versus 21% in Whites/Asians/Pacific Islanders, P=0.006); and by HIV status (64% in HIV positive versus 22% in HIV negative cases, P=0.03).
EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group.
Little is known about the etiology of neuroblastoma, the most common cancer in infancy. In this study, we examined maternal exposure to ambient air toxics in pregnancy in relation to neuroblastoma in the child. We ascertained all cases of neuroblastoma listed in the California Cancer Registry 1990-2007 that could be linked to a California birth certificate, and controls were selected at random from California birth records. Average air toxics exposures during pregnancy were determined based upon measures from community-based air pollution monitors. The study included 75 cases and 14,602 controls who lived with 5 kilometers of an air pollution monitor, and we additionally examined results for those living within a smaller radius around the monitor (2.5 km). Logistic regression was used to determine the risk of neuroblastoma with one interquartile range increase in air toxic exposure. Neuroblastoma risk was increased with higher maternal exposure to carbon tetrachloride (OR=2.65, 95%CI 1.07, 6.53) and polycyclic aromatic hydrocarbons (OR=1.39, 95%CI 1.05, 1.84), particularly indeno(1,2,3-cd)pyrene and dibenz(a,h)anthracene. Hexavalent chromium was associated with neuroblastoma at the 5 km distance (OR=1.32, 95%CI 1.00, 1.74) but not at the 2.5 km distance. This is one of the first studies to report associations between neuroblastoma and these air toxics.
Air pollution; Benzene; Embryonal neoplasms; Neuroblastoma; Prenatal Exposure; Childhood cancer epidemiology; Risk factors
In the mid 1980s, there was a rise in incidence rates of childhood brain tumors (CBT) in the United States that appeared to stabilize at a higher rate in the early 1990s. An updated analysis of the pattern of CBT over the past 2 decades, with commentary on whether the elevated incidence rate has continued, is past due.
We used Surveillance Epidemiology and End Results (SEER) data to examine trends in incidence of CBT from 1973 through 2009. We examined age-adjusted incidence rates (AAIRs) and secular trends for all malignant brain tumors combined (SEER classification) by histologic tumor type and anatomic site.
The incidence of CBT remained stable from 1987-2009 (annual percent change (APC)=0.10; 95% confidence intervals (CI): −0.39, 0.61) with an AAIR for all CBT of 3.32 (95%CI: 3.22, 3.42). The stability of rates in these two decades contrast the change that occurred in the mid-1980s (1983-1986), when the incidence of CBT increased by 53% (APC=14.06; 95%CI: 4.05, 25.0). From 1983-1986, statistically significant rate increases were observed for pilocytic astrocytoma, PNET/medulloblastoma, and mixed glioma. Further, the rate of increase in pilocytic astrocytoma was similar to the rate of decrease for astrocytomas NOS from 1981-2009, suggesting a change from a more general to more specific classification.
After the increase in rates in the mid-1980s, rates of CBT over the past two decades have stabilized. Changes in incidence rates of subtypes of tumors over this time period reflect changes both in classification of CBT and in diagnostic techniques.
childhood brain tumors; gender; histology; incidence rates; pediatric cancer; secular trends; SEER
Exposure to air pollution during pregnancy has been linked to the risk of childhood cancer, but the evidence remains inconclusive. In the present study, we used land use regression modeling to estimate prenatal exposures to traffic exhaust and evaluate the associations with cancer risk in very young children. Participants in the Air Pollution and Childhood Cancers Study who were 5 years of age or younger and diagnosed with cancer between 1988 and 2008 were had their records linked to California birth certificates, and controls were selected from birth certificates. Land use regression–based estimates of exposures to nitric oxide, nitrogen dioxide, and nitrogen oxides were assigned based on birthplace residence and temporally adjusted using routine monitoring station data to evaluate air pollution exposures during specific pregnancy periods. Logistic regression models were adjusted for maternal age, race/ethnicity, educational level, parity, insurance type, and Census-based socioeconomic status, as well as child's sex and birth year. The odds of acute lymphoblastic leukemia increased by 9%, 23%, and 8% for each 25-ppb increase in average nitric oxide, nitrogen dioxide, and nitrogen oxide levels, respectively, over the entire pregnancy. Second- and third-trimester exposures increased the odds of bilateral retinoblastoma. No associations were found for annual average exposures without temporal components or for any other cancer type. These results lend support to a link between prenatal exposure to traffic exhaust and the risk of acute lymphoblastic leukemia and bilateral retinoblastoma.
air pollution; epidemiology; leukemia; neoplasms; retinoblastoma
Cytoplasmic inclusions known as Lewy bodies, a hallmark of Parkinson’s disease (PD) pathology, may protect against cytotoxic proteins. Since the ubiquitin-proteasome system (UPS) degrades cytotoxic proteins, dysfunction in the UPS may contribute to PD etiology. Our goal in this study was to screen pesticides for proteasome inhibition and investigate (i) whether ambient exposures to pesticides that inhibit the UPS increase PD risk and (ii) whether genetic variation in candidate genes of the UPS pathway modify those increased risks. We assessed 26S UPS activity in SK-N-MCu cells by fluorescence. We recruited idiopathic PD cases (n=360) and population-based controls (n=816) from three counties in California with considerable commercial agriculture. We determined ambient pesticide exposure by our validated GIS-based model utilizing residential and workplace address histories. We limited effect measure modification assessment to Caucasians (287 cases, 453 controls). 11 of 28 pesticides we screened inhibited 26S UPS activity at 10μM. Benomyl, cyanazine, dieldrin, endosulfan, metam, propargite, triflumizole, and ziram were associated with increased PD risk. We estimated an odds ratio of 2.14 (95%CI: 1.42,3.22) for subjects with ambient exposure to any UPS-inhibiting pesticide at both residential and workplace addresses; this association was modified by genetic variation in the s-phase kinase-associated protein 1 gene (SKP1; interaction p-value=0.005). Our results provide evidence that UPS-inhibiting pesticides play a role in the etiology of PD and suggest that genetic variation in candidate genes involved in the UPS pathway might exacerbate the toxic effects of pesticide exposures.
epidemiology; gene-environment interaction; Parkinson’s disease; pesticides; ubiquitin-proteasome system
Bladder cancer is the fourth most common cancer in men in the United States, and its recurrence rate is highest among all malignancies. The unmet need for improved strategies for early detection, treatment, and monitoring of the progression of this disease continues to translate into high mortality and morbidity. The quest for advanced diagnostic, therapeutic, and prognostic approaches for bladder cancer is a high priority, which can be achieved by understanding the molecular mechanisms of the initiation and progression of this malignancy. Aberrant DNA methylation in single or multiple cancer-related genes/loci has been found in human bladder tumors and cancer cell lines, and urine sediments, and correlated with many clinicopathological features of this disease, including tumor relapse, muscle-invasiveness, and survival. The present review summarizes the published research on aberrant DNA methylation in connection with human bladder cancer. Representative studies are highlighted to set forth the current state of knowledge, gaps in the knowledgebase, and future directions in this prime epigenetic field of research. Identifying the potentially reversible and ‘drugable’ aberrant DNA methylation events that initiate and promote bladder cancer development can highlight biological markers for early diagnosis, effective therapy and accurate prognosis of this malignancy.
aberrant DNA methylation; animal models; epigenetics; transitional cell carcinoma; tumorigenesis
Adult height is determined by genetics and childhood nutrition, but childhood infections may also play a role. Monozygotic twins are genetically matched and offer an advantage when identifying environmental determinants. In 2005–2007, we examined the association of childhood infections with adult height in 140 height-discordant monozygotic twin pairs from the California Twin Program. To obtain information on childhood infections and growth, we interviewed the mothers of monozygotic twins who differed in self-reported adult height by at least 1-inch (2.5 cm). Within-pair differences in the relative frequency of childhood infections were highly correlated, especially within age groups. A conditional logistic regression analysis demonstrated that more reported episodes of febrile illness occurred in the twin with shorter stature (odds ratio = 2.00, 95% confidence interval: 1.18, 3.40). The association was strongest for differences in the relative frequency of infection during the toddler years (ages 1–5: odds ratio = 3.34, 95% confidence interval: 1.47, 7.59) and was similar when restricted to twin pairs of equal birth length. The association was not explained by differential nutritional status. Measures of childhood infection were associated with height difference in monozygotic twin pairs, independent of genome, birth length, and available measures of diet.
body height; case-control studies; growth; infection; pediatrics; twins
(i) To assess the baseline knowledge of non-medical skin care professionals (estheticians, cosmetologists, massage therapists) on tanning bed use and its association with melanoma; and (ii) to provide preliminary evidence of the potential impact of a fast and simple educational intervention on tanning beds and melanoma on the awareness of non-medical skin care professionals towards skin cancer prevention.
A pre-intervention survey was administered to non-medical skin care professional at salons or spas in Southern California to assess baseline knowledge on tanning and skin cancer. This was followed immediately by a 10-minute oral presentation on tanning bed use and its association with melanoma. One month later, a post-intervention survey was distributed to individuals who attended the initial oral presentation.
Significant changes pre- and post-intervention were found in non-medical skin care professionals’ answer responses to the following: (i) increased speaking to clients about cancer risk with tanning bed use 42–66% (OR 2.44; 95% CI 1.39, 4.30)]; (ii) decreased personal tanning bed use (23–15% [OR 0.61; 95% CI 0.37, 1.00]); and (iii) decreased belief that tanning beds are an excellent cosmetic tool (29–20% [OR 0.60; 95% CI 0.38, 0.96]).
This study provides preliminary evidence that non-medical skin care professionals could be an important source of primary prevention information for reducing the burden of melanoma.
Hepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology.
We matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988–2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n=218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates.
We observed increased risks for hepatoblastoma among children with low [1500–2499 g, Odds Ratio (OR)=2.02, 95% confidence interval (CI) 1.29–3.15] and very low birthweight (<1500 g, OR=15.4, 95% CI 10.7–22.3), preterm birth <33 weeks (OR=7.27, 95% CI 5.00, 10.6), small size for gestational age (OR=1.75, 95% CI 1.25–2.45), and with multiple birth pregnancies (OR=2.52, 95% CI 1.54–4.14). We observed a number of pregnancy and labor complications to be related to hepatoblastoma, including preeclampsia, premature labor, fetal distress, and congenital anomalies.
These findings confirm previously reported associations with low birthweight and preeclampsia. The relation with multiple birth pregnancies has been previously reported and may indicate a relation to infertility treatments.
hepatoblastoma; birth weight; preterm labor; fetal distress; gestational age; pre-eclampsia; multiple birth offspring; risk factors; epidemiology; etiology
Studies have shown that higher solar UV radiation exposure (UVR) may be related to lower risk of some cancers in adults. Recently an ecological study reported lower risks of some cancers among children living in higher UVR cities and countries. In a large population-based case-control study in California we tested the hypothesis that childhood cancers may be influenced by UVR.
Cancers in children ages 0 to 5 years were identified from California Cancer Registry records for 1986–2007 and linked to birth certificate data. Controls were sampled from the birth certificates at a ratio of 20:1. Based on birth address, we assigned UVR exposure in units of Watt-hours/m2 using a geostatistical exposure model developed with data from the National Solar Radiation Database.
For cases with UVR exposure of 5111 Watt-hrs/m2 or above we estimated a reduction in odds of developing acute lymphoblastic leukemia (OR: 0.89, 95% CI: 0.81, 0.99), hepatoblastoma (OR: 0.69, 95% CI: 0.48, 1.00), and non-Hodgkin’s lymphoma (OR: 0.71, 95% CI: 0.50, 1.02) adjusting for mother’s age, mother’s race and child’s year of birth. We also observed a small increase in odds for intracranial/intraspinal embryonal tumors (OR: 1.29, 95% CI: 1.01, 1.65).
Our findings suggest that UVR during pregnancy may decrease the odds of some childhood cancers. Future studies should explore additional factors that may be correlated with UVR exposure and possibly include biomarkers of immune function and vitamin D.
This study shows protective associations of UVR with some childhood cancers.
Rhabdoid tumors are a rare and aggressive cancer subtype which is usually diagnosed in early childhood. Little is known about their etiology. The purpose of this study was to describe the epidemiology of rhabdoid tumors and examine their relation to perinatal characteristics.
We identified 44 atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS) and 61 rhabdoid sarcomas (renal and extra-renal non-CNS tumors) from California Cancer Registry records of diagnoses 1988-2007 among children <6 years of age. We randomly selected 208,178 controls from California birthrolls. Multivariable logistic regression was used to examine associations between rhabdoid tumors and perinatal characteristics.
After adjustment for demographic characteristics, low birthweight (<2500g) strongly increased risk for developing both rhabdoid sarcomas (OR=2.43, 95% CI 1.09, 5.41) and AT/RT (OR=2.99, 95% CI 1.31, 6.84). Both preterm delivery (<37 weeks gestation, OR=2.63, 95% CI 1.34, 5.17) and late term delivery (>42 weeks, OR=3.66, 95% CI 1.54, 8.71) also increased risk of rhabdoid sarcomas. Rhabdoid sarcoma cases (OR=3.08, 95% CI 1.11, 8.55) and AT/RT cases (OR=3.16, 95% CI 1.23, 8.13) also were more likely to be multiple births.
The excess of twin pregnancies may suggest an association with infertility treatments. This is the first population-based epidemiologic study to examine these rare tumors.
rhabdoid tumors; birth characteristics; birthweight; social class; maternal age; multiple birth offspring; premature labor; neonatal intensive care
We investigated comorbidities and endometrial cancer survival by ethnicity because Hispanic whites (HWs) have worse survival than non-Hispanic whites (NHWs).
An endometrial cancer cohort (1992–2004) established with the Surveillance, Epidemiology and End Results-Medicare linked database (n=3286) was followed through 2007. Endometrial cancer-specific and other cause mortality were evaluated with multivariate hazard ratios (mHRs).
HWs were more likely than NHWs to have regional/distant disease (31.7% vs. 24.8%), diabetes (31.7% vs. 11.0%), and hypertension (49.4% vs. 37.6%). HWs had poorer endometrial cancer-specific survival than NHWs (age-adjusted HR=1.28; 95%CI 1.01–1.61), but not after adjustment for tumor characteristics and treatment (mHR=1.02; 95%CI 0.81–1.29). In contrast, even after adjustment for cancer-related factors, other cause mortality in HWs was elevated (mHR=1.27; 95%CI 1.01–1.59), but not after further adjustment for comorbid conditions (mHR=1.07; 95%CI 0.85–1.35).
Comorbidities, particularly diabetes, were more common in HWs than NHWs and impacted other cause mortality. Improving diabetes management may be an effective means of improving other cause mortality. This may be particularly true for HWs, given their particularly high prevalence of diabetes.
endometrial neoplasms; comorbidities; survival; SEER; Medicare
Background: The literature on traffic-related air pollution and childhood cancers is inconclusive, and little is known on rarer cancer types.
Objectives: We sought to examine associations between childhood cancers and traffic-related pollution exposure.
Methods: The present study included children < 6 years of age identified in the California Cancer Registry (born 1998–2007) who could be linked to a California birth certificate (n = 3,590). Controls were selected at random from California birthrolls (n = 80,224). CAlifornia LINE Source Dispersion Modeling, version 4 (CALINE4) was used to generate estimates of local traffic exposures for each trimester of pregnancy and in the first year of life at the address indicated on the birth certificate. We checked our findings by additionally examining associations with particulate matter (≤ 2.5 μm in aerodynamic diameter; PM2.5) pollution measured by community-based air pollution monitors, and with a simple measure of traffic density.
Results: With unconditional logistic regression, a per interquartile range increase in exposure to traffic-related pollution during the first trimester (0.0538 ppm carbon monoxide, estimated using CALINE4) was associated with acute lymphoblastic leukemia [ALL; first trimester odds ratio (OR) = 1.05; 95% CI: 1.01, 1.10]; germ cell tumors (OR = 1.16; 95% CI: 1.04, 1.29), particularly teratomas (OR = 1.26; 95% CI: 1.12, 1.41); and retinoblastoma (OR = 1.11; 95% CI: 1.01, 1.21), particularly bilateral retinoblastoma (OR = 1.16; 95% CI: 1.02, 1.33). Retinoblastoma was also associated with average PM2.5 concentrations during pregnancy, and ALL and teratomas were associated with traffic density near the child’s residence at birth.
Conclusions: We estimated weak associations between early exposure to traffic pollution and several childhood cancers. Because this is the first study to report on traffic pollution in relation to retinoblastoma or germ cell tumors, and both cancers are rare, these findings require replication in other studies.
Citation: Heck JE, Wu J, Lombardi C, Qiu J, Meyers TJ, Wilhelm M, Cockburn M, Ritz B. 2013. Childhood cancer and traffic-related air pollution exposure in pregnancy and early life. Environ Health Perspect 121:1385–1391; http://dx.doi.org/10.1289/ehp.1306761
Recent studies revealed a negative association between acculturation and sun-safe behaviors, possibly mediated by education level, health status, and social networks. We sought to elucidate this relationship by exploring the moderating effects of gender and health insurance on each mediated path. We used data from 496 Latino respondents to the 2005 Health Information National Trends Survey. Acculturation, assessed by a four-item index, was the primary predictor; use of sunscreen and protective clothing were the primary outcomes, assessed by frequency scales. Moderated mediation was tested with an established causal moderation method. The mediated association between acculturation, education level and sunscreen use might be stronger among women than men (P < 0.08). We found no evidence of moderated mediation for use of protective clothing. The findings suggest ways of refining the theoretical and empirical rationale for sun safety research and interventions with Latinos. Studies should replicate these models with longitudinal data.
Acculturation; Sun-safe behaviors; Latinos; Moderated mediation; Sociodemographic factors
The etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California children.
We identified 609 retinoblastoma cases (420 unilateral, 187 bilateral, and 2 with laterality unknown) from California Cancer Registry records of diagnoses 1988–2007 among children <6 years of age. We randomly selected 209,051 controls from California birthrolls. The source of most study data was birth certificates. Multivariable logistic regression was used to examine associations between retinoblastoma and perinatal characteristics.
Bilateral retinoblastoma was associated with greater paternal age [for fathers over 35, crude Odds Ratio (OR)=1.73, 95% Confidence Interval (CI) 1.20, 2.47] and with twin births (OR=1.93, 95% CI 0.99, 3.79). Among unilateral cases, we observed an increased risk among children of US-born Hispanic mothers (OR=1.34, 95% CI 1.01, 1.77) while a decreased risk was observed for infants born to mothers with less than 9 years of education (OR=0.70, 95% CI 0.49–1.00), a group that consisted primarily of mothers born in Mexico. We observed that maternal infection in pregnancy with any STD (OR=3.59, 95% CI 1.58, 8.15) was associated with bilateral retinoblastoma.
This study supports the findings of previous investigations reporting associations between parental age, HPV infection and retinoblastoma.
Anemia; Assisted Reproductive Techniques; Human papillomavirus; Mexican Americans; Rhesus blood group system; Risk factors; Social class
To provide patients and physicians with population-based estimates of mortality from prostate cancer or other causes depending upon the primary treatment modality, stratified by patient age, tumor stage and grade.
We conducted a 10-year competing-risk analysis of 45,440 men diagnosed with clinically localized (T1 or T2) prostate cancer in California during 1995–1998. Information on patient characteristics, primary treatment and cause of death was obtained from the California Cancer Registry.
In this population-based cohort, the most common primary treatment was surgery (40.4%), followed by radiotherapy (29.1%), conservative management (20.8%), and androgen deprivation therapy (ADT) monotherapy (9.8%). Prostate cancer mortality differed significantly (p < 0.0001) across treatment groups among patients <80 years at diagnosis with moderately or poorly differentiated disease; the 10-year disease-specific mortality rates were generally highest for men treated with ADT monotherapy [range: 3.3% (95% CI=0.8–12.5%) to 53.8% (95% CI=34.4–72.2%)], intermediate for men treated with conservative management [range: 1.7% (95% CI=0.7–4.6%) to 30.0% (95% CI=16.2–48.8%] or radiotherapy [range: 3.2% (95% CI=1.8–5.5%) to 18.3% (95% CI=15.1–22.0%)], and lowest for men treated with surgery [range: 1.2% (95% CI=0.8–1.7%) to 11.0% (95% CI=8.4–14.2%)].
The cause-specific mortality estimates provided by this observational study can help patients and physicians better understand the expected long-term outcomes of localized prostate cancer given the initial treatment choice and practice patterns in the general population.
Prostate cancer; treatment; mortality; cohort study; California Cancer Registry
Few studies have examined associations of birth outcomes with toxic air pollutants (air toxics) in traffic exhaust. This study included 8,181 term low birth weight (LBW) children and 370,922 term normal-weight children born between January 1, 1995, and December 31, 2006, to women residing within 5 miles (8 km) of an air toxics monitoring station in Los Angeles County, California. Additionally, land-use-based regression (LUR)-modeled estimates of levels of nitric oxide, nitrogen dioxide, and nitrogen oxides were used to assess the influence of small-area variations in traffic pollution. The authors examined associations with term LBW (≥37 weeks’ completed gestation and birth weight <2,500 g) using logistic regression adjusted for maternal age, race/ethnicity, education, parity, infant gestational age, and gestational age squared. Odds of term LBW increased 2%–5% (95% confidence intervals ranged from 1.00 to 1.09) per interquartile-range increase in LUR-modeled estimates and monitoring-based air toxics exposure estimates in the entire pregnancy, the third trimester, and the last month of pregnancy. Models stratified by monitoring station (to investigate air toxics associations based solely on temporal variations) resulted in 2%–5% increased odds per interquartile-range increase in third-trimester benzene, toluene, ethyl benzene, and xylene exposures, with some confidence intervals containing the null value. This analysis highlights the importance of both spatial and temporal contributions to air pollution in epidemiologic birth outcome studies.
air pollution; benzene; fetal growth retardation; hydrocarbons, aromatic; infant, low birth weight; pregnancy