Sex differences in associations between birth characteristics and childhood cancers: a five-state registry-linkage study.

BACKGROUND: There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. METHODS: Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction < 0.01) by sex was evaluated for each characteristic in each cancer. RESULTS: Males comprised > 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction < 0.01) including gestational age for ALL (female, 40 vs. 37-39 weeks OR: 0.84, 95% CI 0.73-0.97) and ependymoma (female, 40 vs. 37-39 OR: 1.78, 95% CI 1.14-2.79; female, ≥ 41 OR: 2.01. 95% CI 1.29-3.14), birth order for AML (female, ≥ 3rd vs. 1st OR: 1.39, 95% CI 1.01-1.92), maternal education for Hodgkin lymphoma (male, any college vs. < high school[HS] OR: 1.47, 95% CI 1.03-2.09) and Wilms tumor (female, any college vs. HS OR: 0.74, 95% CI 0.59-0.93), maternal race/ethnicity for neuroblastoma (male, black vs. white OR: 2.21, 95% CI 1.21-4.03; male, Hispanic vs. white OR: 1.86, 95% CI 1.26-2.75; female, Asian/Pacific Islander vs. white OR: 0.28, 95% CI 0.12-0.69), and paternal age (years) for hepatoblastoma in males (< 24 vs. 25-29 OR: 2.17, 95% CI 1.13-4.19; ≥ 35 vs. 25-29 OR: 2.44, 95% CI 1.28-4.64). CONCLUSIONS: These findings suggest etiologic heterogeneity by sex for childhood cancers for gestational age, maternal education, and race/ethnicity and paternal age.

Parental Age and Risk of Infant Leukaemia: A Pooled Analysis.

BACKGROUND: Infant leukaemia (IL) is extremely rare with fewer than 150 cases occurring each year in the United States. Little is known about its causes. However, recent evidence supports a role of de novo mutations in IL aetiology. Parental age has been associated with several adverse outcomes in offspring, including childhood cancers. Given the role of older parental age in de novo mutations in offspring, we carried out an analysis of parental age and IL. METHODS: We evaluated the relationship between parental age and IL in a case-control study using registry data from New York, Minnesota, California, Texas, and Washington. Records from 402 cases [219 acute lymphoblastic leukaemia (ALL), 131 acute myeloid leukaemia (AML), and 52 other] and 45 392 controls born during 1981-2004 were analysed. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Estimates were adjusted for infant sex, birth year category, maternal race, state, and mutually adjusted for paternal or maternal age, respectively. RESULTS: Infants with mothers' age ≥40 years had an increased risk of developing AML (OR 4.80, 95% CI 1.80, 12.76). In contrast, paternal age <20 was associated with increased risk of ALL (OR 3.69, 95% CI 1.62, 8.41). CONCLUSION: This study demonstrates increased risk of infant ALL in relation to young paternal age. Given record linkage, there is little concern with recall or selection bias, although data are lacking on MLL gene status and other potentially important variables. Parent of origin effects, de novo mutations, and/or carcinogenic exposures may be involved in IL aetiology.

Congenital anomalies associated with oil and gas development and resource extraction: a population-based retrospective cohort study in Texas.

BACKGROUND: Oil and gas extraction-related activities produce air and water pollution that contains known and suspected teratogens. To date, health impacts of in utero exposure to these activities is largely unknown. OBJECTIVE: We investigated associations between in utero exposure to oil and gas extraction activity in Texas, one of the highest producers of oil and gas, and congenital anomalies. METHODS: We created a population-based birth cohort between 1999 and 2009 with full maternal address at delivery and linked to the statewide congenital anomaly surveillance system (n = 2,234,138 births, 86,315 cases). We examined extraction-related exposures using tertiles of inverse distance-squared weighting within 5 km for drilling site count, gas production, oil production, and produced water. In adjusted logistic regression models, we calculated odds of any congenital anomaly and 10 specific organ sites using two comparison groups: 1) 5 km of future drilling sites that are not yet operating (a priori main models), and 2) 5-10 km of an active well. RESULTS: Using the temporal comparison group, we find increased odds of any congenital anomaly in the highest tertile exposure group for site count (OR: 1.25; 95% CI: 1.21, 1.30), oil production (OR: 1.08; 95% CI: 1.04, 1.12), gas production (1.20; 95% CI: 1.17, 1.23), and produced water (OR: 1.17; 95% CI: 1.14, 1.20). However, associations did not follow a consistent exposure-response pattern across tertiles. Associations are highly attenuated, but still increased, with the spatial comparison group in the highest tertile exposure group. Cardiac and circulatory defects are strongly and consistently associated with all exposure metrics. SIGNIFICANCE: Increased odds of congenital anomalies, particularly cardiac and circulatory defects, were associated with exposures related to oil and gas extraction in this large population-based study. Future research is needed to confirm findings, examine specific exposure pathways, and identify potential avenues to reduce exposures among local populations. IMPACT: About 5% of the U.S. population (~17.6 million people) resides within 1.6 km of an active oil or gas extraction site, yet the influence of this industry on population health is not fully understood. In this analysis, we examined associations between oil and gas extraction-related exposures and congenital anomalies by organ site using birth certificate and congenital anomaly surveillance data in Texas (1999-2009). Increased odds of congenital anomalies, particularly cardiac and circulatory defects, were associated with exposures related to oil and gas extraction in this large population-based study. Future research is needed to confirm these findings.

Are children with birth defects at higher risk of childhood cancers?

Birth defects may influence the risk of childhood cancer development through a variety of mechanisms. The rarity of both birth defects and childhood cancers makes it challenging to study these associations, particularly for the very rare instances of each. To address this limitation, the authors conducted a record linkage-based cohort study among Texas children born between 1996 and 2005. Birth defects in the cohort were identified through the Texas Birth Defects Registry, and children who developed cancer were identified by using record linkage with Texas Cancer Registry data. Over 3 million birth records were included; 115,686 subjects had birth defects, and there were 2,351 cancer cases. Overall, children with a birth defect had a 3-fold increased risk of developing cancer (incidence rate ratio (IRR) = 3.05, 95% confidence interval (CI): 2.65, 3.50), with germ cell tumors (IRR = 5.19, 95% CI: 2.67, 9.41), retinoblastomas (IRR = 2.34, 95% CI: 1.21, 4.16), soft-tissue sarcomas (IRR = 2.12, 95% CI: 1.09, 3.79), and leukemias (IRR = 1.39, 95% CI: 1.09, 1.75) having statistically significant elevated point estimates. All birth defect groups except for musculoskeletal had increased cancer incidence. Untangling the strong relation between birth defects and childhood cancers could lead to a better understanding of the genetic and environmental factors that affect both conditions.

Associations between residential proximity to oil and gas extraction and hypertensive conditions during pregnancy: a difference-in-differences analysis in Texas, 1996-2009.

BACKGROUND: Oil and gas extraction produces air pollutants that are associated with increased risks of hypertension. To date, no study has examined residential proximity to oil and gas extraction and hypertensive conditions during pregnancy. This study quantifies associations between residential proximity to oil and gas development on gestational hypertension and eclampsia. METHODS: We utilized a population-based retrospective birth cohort in Texas (1996-2009), where mothers reside <10 km from an active or future drilling site (n = 2 845 144.) Using full-address data, we linked each maternal residence at delivery to assign exposure and evaluate this exposure with respect to gestational hypertension and eclampsia. In a difference-in-differences framework, we model the interaction between maternal health before (unexposed) or after (exposed) the start of drilling activity (exposed) and residential proximity near (0-1, >1-2 or >2-3 km) or far (≥3-10 km) from an active or future drilling site. RESULTS: Among pregnant women residing 0-1 km from an active oil or gas extraction site, we estimate 5% increased odds of gestational hypertension [95% confidence interval (CI): 1.00, 1.10] and 26% increased odds of eclampsia (95% CI: 1.05, 1.51) in adjusted models. This association dissipates in the 1- to 3-km buffer zones. In restricted models, we find elevated odds ratios among maternal ages ≤35 years at delivery, maternal non-Hispanic White race, ≥30 lbs gained during pregnancy, nulliparous mothers and maternal educational attainment beyond high school. CONCLUSIONS: Living within 1 km of an oil or gas extraction site during pregnancy is associated with increased odds of hypertensive conditions during pregnancy.

Birth order and risk of childhood cancer: a pooled analysis from five US States.

The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case-control dataset. The subjects were drawn from population-based registries of cancers and births in California, Minnesota, New York, Texas and Washington. We included 17,672 cases <15 years of age who were diagnosed from 1980 to 2004 and 57,966 randomly selected controls born 1970-2004, excluding children with Down syndrome. We calculated odds ratios and 95% confidence intervals using logistic regression, adjusted for sex, birth year, maternal race, maternal age, multiple birth, gestational age and birth weight. Overall, we found an inverse relationship between childhood cancer risk and birth order. For children in the fourth or higher birth order category compared to first-born children, the adjusted OR was 0.87 (95% CI: 0.81, 0.93) for all cancers combined. When we examined risks by cancer type, a decreasing risk with increasing birth order was seen in the central nervous system tumors, neuroblastoma, bilateral retinoblastoma, Wilms tumor and rhabdomyosarcoma. We observed increased risks with increasing birth order for acute myeloid leukemia but a slight decrease in risk for acute lymphoid leukemia. These risk estimates were based on a very large sample size, which allowed us to examine rare cancer types with greater statistical power than in most previous studies, however the biologic mechanisms remain to be elucidated.

Assessing the effectiveness of vehicle emission regulations on improving perinatal health: a population-based accountability study.

BACKGROUND: Since the 1990s, extensive regulations to reduce traffic-related air pollution (TRAP) have been implemented, yet the effectiveness of these regulations has not been assessed with respect to improving infant health. In this study, we evaluate how infant health risks associated with maternal residences near highways during pregnancy have changed over time. METHODS: We created a population-based retrospective birth cohort with geocoded residential addresses in Texan metropolitan areas from 1996 through 2009 (n = 2 259 411). We compared term birthweight (37-42 weeks of gestation) among maternal residences <300 m from a highway (high TRAP exposure) (n = 394 346) and 500-3500 m from a highway (comparison group) (n = 1 865 065). We implemented linear regressions to evaluate interactions between high TRAP exposure and birth year, adjusting for demographics, socioeconomic status and neighbourhood context. In addition, we used propensity score matching to further reduce residual confounding. RESULTS: From 1996 to 2009, outdoor NO2 decreased by 51.3%, based on regulatory monitoring data in Texas. Among pregnant women who resided in the high TRAP zone during pregnancy, interaction terms between residential location and birth year show that birthweight increased by 1.1 g [95% confidence interval CI): 0.7, 1.5) in unadjusted models and 0.3 g (95% CI: 0.0, 0.6) in matched models. Time-stratified models also show decreasing impacts of living in high TRAP areas on birthweight when comparing infants born in 1996-97 with 2008-09. Sensitivity analyses with alternative exposure and control groups show consistent results. CONCLUSIONS: Infant health risks associated with maternal residence near highways have reduced over time, paralleling regulatory measures to improve exhaust pipe emissions.

Associations between Residential Proximity to Oil and Gas Drilling and Term Birth Weight and Small-for-Gestational-Age Infants in Texas: A Difference-in-Differences Analysis.

BACKGROUND: Oil and natural gas extraction may produce environmental pollution at levels that affect reproductive health of nearby populations. Available studies have primarily focused on unconventional gas drilling and have not accounted for local population changes that can coincide with drilling activity. OBJECTIVE: Our study sought to examine associations between residential proximity to oil and gas drilling and adverse term birth outcomes using a difference-in-differences study design. METHODS: We created a retrospective population-based term birth cohort in Texas between 1996 and 2009 composed of mother-infant dyads (n=2,598,025) living <10km from an oil or gas site. We implemented a difference-in-differences approach to estimate associations between drilling activities and infant health: term birth weight and term small for gestational age (SGA). Using linear and logistic regression, we modeled interactions between births before (unexposed) or during (exposed) drilling activity and residential proximity near (0-1, 1-2, or 2-3km) or far (3-10km) from an active or future drilling site, adjusting for individual- and neighborhood-level characteristics. RESULTS: The adjusted mean difference in term birth weight for mothers living 0-1 vs. 3-10km from a current or future drilling site was -7.3g [95% confidence interval (CI): -11.6, -3.0] for births during active vs. future drilling. The corresponding adjusted odds ratio for SGA was 1.02 (95% CI: 0.98, 1.06). Negative associations with term birth weight were observed for the 1-2 and 2-3km near groups, and no consistent differences were identified by type of drilling activity. Larger, though imprecise, adverse associations were found for infants born to Hispanic women, women with the lowest educational attainment, and women living in cities. CONCLUSIONS: Residing near oil and gas drilling sites during pregnancy was associated with a small reduction in term birth weight but not SGA, with some evidence of environmental injustices. Additional work is needed to investigate specific drilling-related exposures that might explain these associations. https://doi.org/10.1289/EHP7678.

Risks of childhood cancer among Texas watersheds, based on mothers' living locations at the time of birth.

Cancer is the most common fatal disease among US children. The fetus has reduced resistance to toxic injury and is especially prone to mutagenic injury because of the high rate of cell division. A fetus can be exposed to environmental toxins through maternal consumption of contaminated water. The objective of this study was to estimate the incidence risk for childhood cancers within each watershed in Texas. The approach modeled risk for 19 cancer histotypes incorporating correlations among the cancer types and spatial correlation. Several watersheds in a very large area known as the Central Great Plains of North Texas were associated with increased risk for astrocytoma. Two watersheds near Houston, Buffalo-San Jacinto and West Galveston Bay, had increased risk for renal cancer and acute lymphoid leukemia, respectively. A watershed in South Texas, the South Laguna Madre, had increased risk for atypical leukemias. The possibility that waterborne toxins cause these childhood cancers should be investigated further.

Childhood cancer among twins and higher order multiples.

Although several studies have found no change or a decreased risk of childhood cancer in twins, few have controlled for potential confounders such as birth weight. We examined the association of birth plurality and childhood cancer in pooled data from five U.S. states (California, Minnesota, New York, Texas, and Washington) using linked birth-cancer registry data. The data, excluding children with Down syndrome or who died before 28 days of life, included 17,672 cases diagnosed from 1980 to 2004 at ages 28 days to 14 years and 57,966 controls with all cases and controls born from 1970 to 2004. Analyses were restricted to children weighing

Reproductive factors and hormone use and risk of adult gliomas.

Previous research suggests there may be a hormonal influence on glioma risk as evidenced by lower rates in females, change in incidence rates around ages at menarche and menopause, and presence of hormone receptors in glial tumors. Using the large San Francisco Bay Area Adult Glioma Study, we investigated whether reported reproductive factors and hormone use were associated with gliomas overall or with histologic subtypes among female cases (n = 619) and controls (n = 650). We found that reproductive factors were generally not associated with gliomas. Weak to moderately elevated odds ratios were observed for self-reported later age at menarche (14+ vs. 12-13 years old: adjusted odds ratio (AOR) = 1.39, 95% confidence interval (CI): 1.02-1.89), particularly for non-glioblastoma histologies (AOR = 1.64, 95% CI: 1.11-2.43). Inverse associations were observed for ever self-reported use of exogenous hormones (oral contraceptive use: AOR = 0.72, 95% CI: 0.53-0.99; postmenopausal hormone use: AOR = 0.56, CI: 0.37-0.84). However, cumulative hormone exposure defined multiple ways demonstrated no clear pattern of association. The results of this study suggest that any protective effect of hormones on gliomas may be limited to exogenous hormones, but a more detailed history of exogenous hormone use is needed to confirm findings.

Parental age and risk of childhood cancer: a pooled analysis.

BACKGROUND: Few risk factors for childhood cancer are well-established. We investigated whether advancing parental age increases childhood cancer risk. METHODS: We assessed the relationship between parental age and childhood cancer in a case-control study using pooled population-based data. Our pooling was based on linked cancer and birth registry records from New York, Washington, Minnesota, Texas, and California. Subjects included 17,672 cancer cases diagnosed at ages 0-14 years during 1980-2004 and 57,966 controls born during 1970-2004. Individuals with Down syndrome were excluded. Odds ratios and 95% confidence intervals were calculated by logistic regression for the association between parental age and childhood cancer after adjustment for sex, birth weight, gestational age, birth order, plurality, maternal race, birth year, and state. RESULTS: Positive linear trends per 5-year maternal age increase were observed for childhood cancers overall (odds ratio = 1.08 [95% confidence interval = 1.06-1.10]) and 7 of the 10 most frequent diagnostic groups: leukemia (1.08 [1.05-1.11]), lymphoma (1.06 [1.01-1.12]), central nervous system tumors (1.07 [1.03-1.10]), neuroblastoma (1.09 [1.04-1.15]), Wilms' tumor (1.16 [1.09-1.22]), bone tumors (1.10 [1.00-1.20]), and soft tissue sarcomas (1.10 [1.04-1.17]). No maternal age effect was noted for retinoblastoma, germ cell tumors, or hepatoblastoma. Paternal age was not independently associated with most childhood cancers after adjustment for maternal age. CONCLUSIONS: Our results suggest that older maternal age increases risk for most common childhood cancers. Investigation into possible mechanisms for this association is warranted.

Urban versus rural residence and occurrence of septal heart defects in Texas.

BACKGROUND: There is conflicting information on the association between urban/rural residence of mothers and atrial septal defect (ASD) or ventricular septal defect (VSD) in their offspring. Few studies have compared multiple measures of urban/rural residence. METHODS: Data were taken from the Texas Birth Defects Registry, 1999-2003. Poisson regression was used to compare crude and adjusted birth prevalence. RESULTS: Three broad urban/rural measures, namely, the rural urban continuum code (RUCC), urban influence code (UIC), and rural urban commuting area (RUCA), were correlated with each other, but much less correlated with percentage of land in crops. ASD showed few consistent patterns with RUCC, UIC, and RUCA but was more prevalent in counties with higher cropland percentage. For example, counties with > or =50% cropland had a prevalence ratio (PR) for isolated ASD of 3.49 (95% confidence interval [CI]: 2.85-4.24) compared to counties with <15% cropland. VSD was less prevalent in rural areas using RUCC, UIC, and RUCA. For example, for isolated VSD, small towns/rural areas had a PR of 0.64 (95% CI: 0.51-0.78) compared to urban core areas using RUCA. The pattern was seen among mild cases of VSD but not among severe cases. VSD was not associated with percentage cropland. CONCLUSIONS: The measure of urban/rural status can greatly affect associations with certain birth defects. More prevalent ASD in areas with greater percentage cropland suggests that agricultural chemicals may be relevant. Mild cases of VSD but not severe cases were less prevalent in rural areas, suggesting that variation in detection may be largely responsible.

Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.

IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

Risk of childhood cancers associated with residence in agriculturally intense areas in the United States.

BACKGROUND: The potential for widespread exposure to agricultural pesticides through drift during application raises concerns about possible health effects to exposed children living in areas of high agricultural activity. OBJECTIVES: We evaluated whether residence in a county with greater agricultural activity was associated with risk of developing cancer in children < 15 years of age. METHODS: Incidence data for U.S. children 0-14 years of age diagnosed with cancer between 1995 and 2001 were provided by member registries of the North American Association of Central Cancer Registries. We determined percent cropland for each county using agricultural census data, and used the overall study distribution to classify agriculturally intense counties. We estimated odds ratios and 95% confidence intervals for all ages and 5-year age groups for total cancers and selected cancer sites using logistic regression. RESULTS: Our study results showed statistically significant increased risk estimates for many types of childhood cancers associated with residence at diagnosis in counties having a moderate to high level of agricultural activity, with a remarkably consistent dose-response effect seen for counties having >or= 60% of the total county acreage devoted to farming. Risk for different cancers varied by type of crop. CONCLUSIONS: Although interpretation is limited by the ecologic design, in this study we were able to evaluate rarer childhood cancers across a diverse agricultural topography. The findings of this exploratory study support a continued interest in the possible impact of long-term, low-level pesticide exposure in communities located in agriculturally intense areas.

Geographic risk modeling of childhood cancer relative to county-level crops, hazardous air pollutants and population density characteristics in Texas.

BACKGROUND: Childhood cancer has been linked to a variety of environmental factors, including agricultural activities, industrial pollutants and population mixing, but etiologic studies have often been inconclusive or inconsistent when considering specific cancer types. More specific exposure assessments are needed. It would be helpful to optimize future studies to incorporate knowledge of high-risk locations or geographic risk patterns. The objective of this study was to evaluate potential geographic risk patterns in Texas accounting for the possibility that multiple cancers may have similar geographic risks patterns. METHODS: A spatio-temporal risk modeling approach was used, whereby 19 childhood cancer types were modeled as potentially correlated within county-years. The standard morbidity ratios were modeled as functions of intensive crop production, intensive release of hazardous air pollutants, population density, and rapid population growth. RESULTS: There was supportive evidence for elevated risks for germ cell tumors and "other" gliomas in areas of intense cropping and for hepatic tumors in areas of intense release of hazardous air pollutants. The risk for Hodgkin lymphoma appeared to be reduced in areas of rapidly growing population. Elevated spatial risks included four cancer histotypes, "other" leukemias, Central Nervous System (CNS) embryonal tumors, CNS other gliomas and hepatic tumors with greater than 95% likelihood of elevated risks in at least one county. CONCLUSION: The Bayesian implementation of the Multivariate Conditional Autoregressive model provided a flexible approach to the spatial modeling of multiple childhood cancer histotypes. The current study identified geographic factors supporting more focused studies of germ cell tumors and "other" gliomas in areas of intense cropping, hepatic cancer near Hazardous Air Pollutant (HAP) release facilities and specific locations with increased risks for CNS embryonal tumors and for "other" leukemias. Further study should be performed to evaluate potentially lower risk for Hodgkin lymphoma and malignant bone tumors in counties with rapidly growing population.

DNA repair polymorphisms XRCC1 and MGMT and risk of adult gliomas.

X-ray cross complementing group 1 (XRCC1) and O6-methylguanine-DNA methyltransferase (MGMT) are pivotal repair genes focused on repairing lesions due to ionizing radiation, alkylating agents, and oxidative DNA damage, risk factors previously linked to gliomas. Using the population based San Francisco Adult Glioma study, we evaluated associations between XRCC1 Arg399Gln, MGMT Leu84Phe, and MGMT Ile143Val polymorphisms with glioma risk among white cases (n = 441 to 453) and controls (n = 487 to 526). We found no evidence of an association between XRCC1 genotypes and glioma. We observed a weak positive association for the MGMT Leu84Phe polymorphism (Leu or Phe/Phe versus Leu/Leu: adjusted OR = 1.26; CI 0.90-1.75) and the MGMT Ile143Val polymorphism (Ile or Val/Val versus Ile/Ile: adjusted OR = 1.20; CI 0.85-1.71).

Associations between multiple green space measures and birth weight across two US cities.

INTRODUCTION: Several measures of green space exposure have been used in epidemiological research, but their relevance to health, and representation of exposure pathways, remains unclear. Here we examine the relationships between multiple urban green space metrics and associations with term birth weight across two diverse US cities. METHODS: We used Vital Statistics data to create a birth cohort from 2005 to 2009 in the cities of Portland, Oregon (n = 90,265) and Austin, Texas (n = 88,807). These cities have similar green space levels but very different population and contextual characteristics. Green space metrics derived from mother's full residential address using multiple buffer distances (50-1000m) included: Landsat Normalized Difference Vegetation Index (NDVI), % tree cover, % green space, % street tree buffering, and access to parks (using US EPA EnviroAtlas Data). Correlation between green space metrics were assessed and mixed models were used to determine associations with term birth weight, controlling for a comprehensive set of individual and neighborhood factors. City-specific models were run to determine how contextual and population differences affected green space associations with birth weight. RESULTS: We observed moderate to high degrees of correlation between different green space metrics (except park access), with similar patterns between cities. Unadjusted associations demonstrated consistent protective effects of NDVI, % green space, % tree cover, and % street tree buffering for most buffer sizes on birth weight; however, in fully adjusted models most metrics were no longer statistically significant and no clear patterns remained. For example, in Austin the difference in birth weight for the highest versus lowest quartile of % green space within 50m was 38.3g (95% CI: 30.4, 46.1) in unadjusted and -1.5g (98% CI: -8.8, 6.3) in adjusted models compared to 55.7g (95%CI: 47.9, -63.6) and 12.9g (95% CI: 4.4, 21.4) in Portland. Maternal race, ethnicity and education had the largest impact on reducing green space and birth weight associations. However, consistent positive associations were observed for the high density areas of both cities using several green space metrics at small buffer distances. CONCLUSIONS: This study highlights the importance of understanding the individual and contextual factors that may confound and/or modify green space and birth weight associations.