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1.  Epstein-Barr virus patterns in U.S. Burkitt lymphoma tumors from the SEER Residual Tissue Repository during 1979-2009 
Background
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.
Results
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).
Conclusions
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.
doi:10.1111/apm.12078
PMCID: PMC3723754  PMID: 23607450
2.  An exploratory study of ambient air toxics exposure in pregnancy and the risk of neuroblastoma in offspring 
Environmental research  2013;127:1-6.
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.
doi:10.1016/j.envres.2013.09.002
PMCID: PMC3960946  PMID: 24139061
Air pollution; Benzene; Embryonal neoplasms; Neuroblastoma; Prenatal Exposure; Childhood cancer epidemiology; Risk factors
3.  Trends in Childhood Brain Tumor Incidence, 1973-2009 
Journal of neuro-oncology  2013;115(2):153-160.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1007/s11060-013-1212-5
PMCID: PMC4056769  PMID: 23925828
childhood brain tumors; gender; histology; incidence rates; pediatric cancer; secular trends; SEER
4.  Prenatal Exposure to Traffic-related Air Pollution and Risk of Early Childhood Cancers 
American Journal of Epidemiology  2013;178(8):1233-1239.
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.
doi:10.1093/aje/kwt129
PMCID: PMC3792733  PMID: 23989198
air pollution; epidemiology; leukemia; neoplasms; retinoblastoma
5.  Pesticides that Inhibit the Ubiquitin-Proteasome System: Effect Measure Modification by Genetic Variation in SKP1 in Parkinson’s Disease 
Environmental research  2013;126:10.1016/j.envres.2013.08.001.
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.
doi:10.1016/j.envres.2013.08.001
PMCID: PMC3832349  PMID: 23988235
epidemiology; gene-environment interaction; Parkinson’s disease; pesticides; ubiquitin-proteasome system
6.  Alterations of DNA methylome in human bladder cancer 
Epigenetics  2013;8(10):1013-1022.
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.
doi:10.4161/epi.25927
PMCID: PMC3891681  PMID: 23975266
aberrant DNA methylation; animal models; epigenetics; transitional cell carcinoma; tumorigenesis
7.  Childhood Infections and Adult Height in Monozygotic Twin Pairs 
American Journal of Epidemiology  2013;178(4):551-558.
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.
doi:10.1093/aje/kwt012
PMCID: PMC3736755  PMID: 23585330
body height; case-control studies; growth; infection; pediatrics; twins
8.  A simple intervention to reinforce awareness of tanning bed use and skin cancer in non-medical skin care professionals in Southern California 
International journal of dermatology  2012;51(11):1307-1312.
Background
(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.
Methods
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.
Results
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]).
Conclusion
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.
doi:10.1111/j.1365-4632.2011.05425.x
PMCID: PMC4127415  PMID: 23067078
9.  Case-control study of birth characteristics and the risk of hepatoblastoma 
Cancer epidemiology  2013;37(4):390-395.
Background
Hepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.canep.2013.03.004
PMCID: PMC3679264  PMID: 23558166
hepatoblastoma; birth weight; preterm labor; fetal distress; gestational age; pre-eclampsia; multiple birth offspring; risk factors; epidemiology; etiology
10.  Solar UV radiation and cancer in young children 
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Impact
This study shows protective associations of UVR with some childhood cancers.
doi:10.1158/1055-9965.EPI-12-1316
PMCID: PMC3690302  PMID: 23585515
11.  Epidemiology of Rhabdoid Tumors of Early Childhood 
Pediatric blood & cancer  2012;60(1):77-81.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1002/pbc.24141
PMCID: PMC3399923  PMID: 22434719
rhabdoid tumors; birth characteristics; birthweight; social class; maternal age; multiple birth offspring; premature labor; neonatal intensive care
12.  Comorbidites and endometrial cancer survival in Hispanics and non-Hispanic whites 
Cancer causes & control : CCC  2012;24(1):61-69.
Purpose
We investigated comorbidities and endometrial cancer survival by ethnicity because Hispanic whites (HWs) have worse survival than non-Hispanic whites (NHWs).
Methods
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).
Results
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).
Conclusions
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.
doi:10.1007/s10552-012-0090-z
PMCID: PMC3529816  PMID: 23109171
endometrial neoplasms; comorbidities; survival; SEER; Medicare
13.  Childhood Cancer and Traffic-Related Air Pollution Exposure in Pregnancy and Early Life 
Environmental Health Perspectives  2013;121(11-12):1385-1391.
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
doi:10.1289/ehp.1306761
PMCID: PMC3855517  PMID: 24021746
14.  Moderated Mediation Regarding the Sun-Safe Behaviors of U.S. Latinos: Advancing the Theory and Evidence for Acculturation-Focused Research and Interventions 
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.
doi:10.1007/s10903-009-9302-3
PMCID: PMC3810164  PMID: 19937384
Acculturation; Sun-safe behaviors; Latinos; Moderated mediation; Sociodemographic factors
15.  Perinatal characteristics and retinoblastoma 
Cancer causes & control : CCC  2012;23(9):1567-1575.
Purpose
The etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California children.
Methods
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.
Results
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.
Conclusions
This study supports the findings of previous investigations reporting associations between parental age, HPV infection and retinoblastoma.
doi:10.1007/s10552-012-0034-7
PMCID: PMC3429932  PMID: 22843021
Anemia; Assisted Reproductive Techniques; Human papillomavirus; Mexican Americans; Rhesus blood group system; Risk factors; Social class
16.  Treatment and Mortality in Men with Localized Prostate Cancer: A Population-Based Study in California 
Purpose
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.
Methods
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.
Results
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%)].
Conclusion
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.
PMCID: PMC3758138  PMID: 23997838
Prostate cancer; treatment; mortality; cohort study; California Cancer Registry
17.  Assessing the Influence of Traffic-related Air Pollution on Risk of Term Low Birth Weight on the Basis of Land-Use-based Regression Models and Measures of Air Toxics 
American Journal of Epidemiology  2012;175(12):1262-1274.
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.
doi:10.1093/aje/kwr469
PMCID: PMC3372317  PMID: 22586068
air pollution; benzene; fetal growth retardation; hydrocarbons, aromatic; infant, low birth weight; pregnancy
18.  The Effect of Administrative Boundaries and Geocoding Error on Cancer Rates in California 
Geocoding is often used to produce maps of disease rates from the diagnosis addresses of incident cases to assist with disease surveillance, prevention, and control. In this process, diagnosis addresses are converted into latitude/longitude pairs which are then aggregated to produce rates at varying geographic scales such as Census tracts, neighborhoods, cities, counties, and states. The specific techniques used within geocoding systems have an impact on where the output geocode is located and can therefore have an effect on the derivation of disease rates at different geographic aggregations. This paper investigates how county-level cancer rates are affected by the choice of interpolation method when case data are geocoded to the ZIP code level. Four commonly used areal unit interpolation techniques are applied and the output of each is used to compute crude county-level five-year incidence rates of all cancers in California. We found that the rates observed for 44 out of the 58 counties in California vary based on which interpolation method is used, with rates in some counties increasing by nearly 400% between interpolation methods.
doi:10.1016/j.sste.2012.02.005
PMCID: PMC3324674  PMID: 22469490
19.  Ambient Air Pollution and Autism in Los Angeles County, California 
Environmental Health Perspectives  2012;121(3):380-386.
Background: The prevalence of autistic disorder (AD), a serious developmental condition, has risen dramatically over the past two decades, but high-quality population-based research addressing etiology is limited.
Objectives: We studied the influence of exposures to traffic-related air pollution during pregnancy on the development of autism using data from air monitoring stations and a land use regression (LUR) model to estimate exposures.
Methods: Children of mothers who gave birth in Los Angeles, California, who were diagnosed with a primary AD diagnosis at 3–5 years of age during 1998–2009 were identified through the California Department of Developmental Services and linked to 1995–2006 California birth certificates. For 7,603 children with autism and 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. We used conditional logistic regression, adjusting for maternal and perinatal characteristics including indicators of SES.
Results: Per interquartile range (IQR) increase, we estimated a 12–15% relative increase in odds of autism for ozone [odds ratio (OR) = 1.12, 95% CI: 1.06, 1.19; per 11.54-ppb increase] and particulate matter ≤ 2.5 µm (OR = 1.15; 95% CI: 1.06, 1.24; per 4.68-μg/m3 increase) when mutually adjusting for both pollutants. Furthermore, we estimated 3–9% relative increases in odds per IQR increase for LUR-based nitric oxide and nitrogen dioxide exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education.
Conclusion: Measured and estimated exposures from ambient pollutant monitors and LUR model suggest associations between autism and prenatal air pollution exposure, mostly related to traffic sources.
doi:10.1289/ehp.1205827
PMCID: PMC3621187  PMID: 23249813
air pollution; autism; land-use regression; pregnancy; traffic
20.  e-Health Tools for Targeting and Improving Melanoma Screening: A Review 
Journal of Skin Cancer  2012;2012:437502.
The key to improved prognosis for melanoma is early detection and diagnosis, achieved by skin surveillance and secondary prevention (screening). However, adherence to screening guidelines is low, with population-based estimates of approximately 26% for physician-based skin cancer screening and 20–25% for skin self-examination. The recent proliferation of melanoma detection “e-Health” tools, digital resources that facilitate screening in patients often outside of the clinical setting, may offer new strategies to promote adherence and expand the proportion and range of individuals performing skin self-examination. The purpose of this paper is to catalog and categorize melanoma screening e-Health tools to aid in the determination of their efficacy and potential for adoption. The availability and accessibility of such tools, their costs, target audience, and, where possible, information on their efficacy, will be discussed with potential benefits and limitations considered. While e-Health tools targeting melanoma screening are widely available, little has been done to formally evaluate their efficacy and ability to aid in overcoming screening barriers. Future research needs to formally evaluate the potential role of e-Health tools in melanoma prevention.
doi:10.1155/2012/437502
PMCID: PMC3530856  PMID: 23304515
21.  Association between cutaneous melanoma incidence rates among white U.S. residents and county-level estimates of solar ultraviolet exposure 
Background
Recent U.S. studies have raised questions as to whether geographic differences in cutaneous melanoma incidence rates are associated with differences in solar ultraviolet (UV) exposure.
Objectives
To assess the association of solar UV exposure with melanoma incidence rates among U.S. non-Hispanic whites.
Methods
We assessed the association between county-level estimates of average annual solar UV exposure for 1961–1990 and county-level melanoma incidence rates during 2004–2006. We used Poisson multilevel mixed models to calculate incidence density ratios by cancer stage at diagnosis while controlling for individuals' age and sex and for county-level estimates of solar UV exposure, socioeconomic status, and physician density.
Results
Age-adjusted rates of early- and late-stage melanoma were both significantly higher in high solar UV counties than in low solar UV counties. Rates of late-stage melanoma incidence were generally higher among men, but younger women had a higher rate of early-stage melanoma than their male counterparts. Adjusted rates of early-stage melanoma were significantly higher in high solar UV exposure counties among men aged 35 or older and women aged 65 or older.
Limitations
The relationship between individual-level UV exposure and risk for melanoma was not evaluated.
Conclusions
County-level solar UV exposure was associated with the incidence of early-stage melanoma among older U.S. adults but not among younger U.S. adults. Additional studies are needed to determine whether exposure to artificial sources of UV exposure or other factors might be mitigating the relationship between solar UV exposure and risk for melanoma.
doi:10.1016/j.jaad.2011.04.035
PMCID: PMC3206292  PMID: 22018067
solar ultraviolet rays/adverse effects; melanoma/epidemiology; skin neoplasms/epidemiology; population surveillance; incidence; registries; socioeconomic factors; dermatology/manpower
22.  Challenges in Identifying Native Hawaiians and Pacific Islanders in Population-Based Cancer Registries in the U.S 
Lack of disaggregated data for Native Hawaiians and Pacific Islanders (NHPIs) in the U.S. has resulted in severe gaps in understanding health disparities and unique health needs of NHPIs. Telephone interviews were conducted with 272 cancer patients identified by a population-based cancer registry. The self-reported NHPIs status was compared with that identified by the registry. Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated. Alternative NHPIs identification methods were explored. The registry had acceptable sensitivity (89%), specificity (96%) and NPV (99%), but low PPV (62%) in identifying NHPIs. Using additional information on surname and birthplace from the registry improved the identification of NHPIs, but either increased the false positive or decreased the counts of true NHPIs cases. Improved data collection methods and practices in identifying NHPIs in population-based cancer registries are needed and caution in interpreting cancer data for NHPIs is warranted.
doi:10.1007/s10903-010-9381-1
PMCID: PMC3191111  PMID: 20803254
Native Hawaiians and Pacific Islanders; Cancer registry; Birthplace; Surnames
23.  Prostate Cancer and Ambient Pesticide Exposure in Agriculturally Intensive Areas in California 
American Journal of Epidemiology  2011;173(11):1280-1288.
In a population-based case-control study in California's intensely agricultural Central Valley (2005–2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. Cases (n = 173) were obtained from a population-based cancer registry, and controls (n = 162) were obtained from Medicare listings and tax assessor mailings. Past ambient exposures to pesticides/fungicides were derived from residential history and independently recorded pesticide and land-use data, using a novel geographic information systems approach. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide (odds ratio = 1.62, 95% confidence interval: 1.02, 2.59) and a group of organochlorines (odds ratio = 1.64, 95% confidence interval: 1.02, 2.63)) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride). The authors assessed the possibility of selection bias due to less-than-100% enrollment of eligible cases and controls (a critical methodological concern in studies of this kind) and determined that there was little evidence of bias affecting the estimated effect size. This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis.
doi:10.1093/aje/kwr003
PMCID: PMC3121318  PMID: 21447478
fungicides, industrial; hydrocarbons, brominated; pesticides; prostatic neoplasms; selection bias
24.  The expanding melanoma burden in California Hispanics: Importance of socioeconomic distribution, histologic subtype and anatomic location 
Cancer  2010;117(1):152-161.
Background
The incidence patterns and socioeconomic distribution of cutaneous melanoma among Hispanics are poorly understood.
Methods
We obtained population-based incidence data for all Hispanic and Non-Hispanic White (NHW) patients diagnosed with invasive cutaneous melanoma from 1988-2007 in the state of California. Using a neighborhood-level measure of socioeconomic status (SES), we investigated incidence, thickness at diagnosis, histologic subtype, and anatomic site and the relative risk (RR) for thicker (>2mm) versus thinner (≤2mm) tumors at diagnosis for groups categorized by SES.
Results
Age-adjusted melanoma incidence rates per million were higher in NHWs (P <.0001); tumor thickness at diagnosis was greater in Hispanics (P <.0001). Sixty-one percent of melanomas in NHWs occurred in the High SES group. Among Hispanics, only 35% occurred in the High SES group; 22% were of Low SES. Lower SES was associated with thicker tumors (P <.0001); this association was stronger in Hispanics. The relative risk (RR) for thicker versus thinner (≤2mm) tumors in Low-SES versus High-SES NHW men was 1.48 (95% CI, 1.37-1.61); it was 2.18 (95% CI, 1.73-2.74) in Hispanic men. Lower-SES patients had less superficial spreading melanoma subtype (especially among Hispanic men) and more nodular melanoma subtype. Leg/hip melanomas were associated with higher SES in NHW males but with lower SES in Hispanic males.
Conclusions
The socioeconomic distribution of melanoma incidence and tumor thickness differed substantially between Hispanic and NHW Californians, particularly among males. Melanoma prevention efforts targeted to lower-SES Hispanics and increased physician awareness of melanoma patterns among Hispanics are needed.
doi:10.1002/cncr.25355
PMCID: PMC3000884  PMID: 20737564
Melanoma; social class; tumor thickness; Hispanic Americans; race; ethnicity
25.  Traffic-Related Air Toxics and Term Low Birth Weight in Los Angeles County, California 
Environmental Health Perspectives  2011;120(1):132-138.
Background: Numerous studies have linked criteria air pollutants with adverse birth outcomes, but there is less information on the importance of specific emission sources, such as traffic, and air toxics.
Objectives: We used three exposure data sources to examine odds of term low birth weight (LBW) in Los Angeles, California, women when exposed to high levels of traffic-related air pollutants during pregnancy.
Methods: We identified term births during 1 June 2004 to 30 March 2006 to women residing within 5 miles of a South Coast Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. Pregnancy period average exposures were estimated for air toxics, including polycyclic aromatic hydrocarbons (PAHs), source-specific particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) based on a chemical mass balance model, criteria air pollutants from government monitoring data, and land use regression (LUR) model estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of term LBW (< 2,500 g) were examined using logistic regression.
Results: Odds of term LBW increased approximately 5% per interquartile range increase in entire pregnancy exposures to several correlated traffic pollutants: LUR measures of NO, NO2, and NOx, elemental carbon, and PM2.5 from diesel and gasoline combustion and paved road dust (geological PM2.5).
Conclusions: These analyses provide additional evidence of the potential impact of traffic-related air pollution on fetal growth. Particles from traffic sources should be a focus of future studies.
doi:10.1289/ehp.1103408
PMCID: PMC3261935  PMID: 21835727
air pollution; air toxics; intrauterine growth retardation; low birth weight; traffic

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