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
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.
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.
air pollution; autism; land-use regression; pregnancy; traffic
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.
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.
To assess the association of solar UV exposure with melanoma incidence rates among U.S. non-Hispanic whites.
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.
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.
The relationship between individual-level UV exposure and risk for melanoma was not evaluated.
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.
solar ultraviolet rays/adverse effects; melanoma/epidemiology; skin neoplasms/epidemiology; population surveillance; incidence; registries; socioeconomic factors; dermatology/manpower
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.
Native Hawaiians and Pacific Islanders; Cancer registry; Birthplace; Surnames
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.
fungicides, industrial; hydrocarbons, brominated; pesticides; prostatic neoplasms; selection bias
The incidence patterns and socioeconomic distribution of cutaneous melanoma among Hispanics are poorly understood.
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.
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.
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.
Melanoma; social class; tumor thickness; Hispanic Americans; race; ethnicity
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.
air pollution; air toxics; intrauterine growth retardation; low birth weight; traffic
Melanoma incidence has been correlated strongly and positively with both socioeconomic status (SES) and lower latitude and other measures of ambient ultraviolet radiation (UVR). However, because high SES populations may be co-located in areas of high UVR, we assessed their joint influences on melanoma occurrence, so as to better target subpopulations for melanoma education and screening.
We obtained from the California Cancer Registry information regarding 23,564 incident cases of invasive cutaneous melanoma among non-Hispanic white residents between January 1, 1998 and December 31, 2002. We geocoded each case based on residence at diagnosis and linked previously tested neighborhood measures of SES and average annual UVR to calculate age-adjusted incidence rates, rate ratios, and corresponding 95% confidence intervals (CI). Poisson regression was used to calculate multivariately adjusted rate ratios.
UVR was significantly and positively associated with melanoma incidence only among persons living in the top 40% of California neighborhoods ranked by SES. People in neighborhoods of the highest SES and UVR categories had 60% higher rates of melanoma than those from neighborhoods in the lowest categories (rate ratio 1.60; 95% CI 1.02–2.51).
Our findings indicate that UVR and SES interact to influence melanoma occurrence, and suggest that socioeconomic gradients in melanoma incidence are not explained entirely by UVR.
Cancer prevention and early detection educational efforts should be targeted to high SES groups in areas of high UVR exposure. Contextual measures of both SES and UVR should be considered important determinants of melanoma occurrence in future studies.
Melanoma; SES; UV; geocode; risk; model
Numerous studies have associated air pollutant exposures with adverse birth outcomes, but there is still relatively little information to attribute effects to specific emission sources or air toxics. We used three exposure data sources to examine risks of preterm birth in Los Angeles women when exposed to high levels of traffic-related air pollutants - including specific toxics - during pregnancy.
We identified births during 6/1/04-3/31/06 to women residing within five miles of a Southern California Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. We identified preterm cases and, using a risk set approach, matched cases to controls based on gestational age at birth. Pregnancy period exposure averages were estimated for a number of air toxics including polycyclic aromatic hydrocarbons (PAHs), source-specific PM2.5 (fine particulates with aerodynamic diameter less than 2.5 μm) based on a Chemical Mass Balance model, criteria air pollutants based on government monitoring data, and land use regression (LUR) estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of preterm birth were estimated using conditional logistic regression.
Odds of preterm birth increased 6-21% per inter-quartile range increase in entire pregnancy exposures to organic carbon (OC), elemental carbon (EC), benzene, and diesel, biomass burning and ammonium nitrate PM2.5, and 30% per inter-quartile increase in PAHs; these pollutants were positively correlated and clustered together in a factor analysis. Associations with LUR exposure metrics were weaker (3-4% per inter-quartile range increase).
These latest analyses provide additional evidence of traffic-related air pollution's impact on preterm birth for women living in Southern California and indicate PAHs as a pollutant of concern that should be a focus of future studies. Other PAH sources besides traffic were also associated with higher odds of preterm birth, as was ammonium nitrate PM2.5, the latter suggesting potential importance of secondary pollutants. Future studies should focus on accurate modeling of both local and regional spatial and temporal distributions, and incorporation of source information.
Although of great interest and suggested in prior reports, possible α-synuclein (SNCA) gene-environment interactions have not been well investigated in humans.
We used a population-based approach to examine whether the risk of Parkinson's disease (PD) depended on the combined presence of SNCA variations and two important environmental factors, pesticide exposures and smoking.
Similar to recent meta- and pooled analyses, our data suggest a lower PD risk in subjects who were either homozygous or heterozygous for the SNCA REP1 259 genotype, and a higher risk in subjects who were either homozygous or heterozygous for the REP1 263 genotype, especially among subjects with an age of onset ≤68 years. More importantly, while analyses of interactions were limited by small cell sizes, risk due to SNCA variations seemed to vary with pesticide exposure and smoking, especially in younger onset cases, suggesting an age-of-onset effect.
α-Synuclein; Pesticides; Parkinson's disease; Smoking; Age of onset; Paraquat; Interaction; REP1
Human, animal and cell models support a role for pesticides in the etiology of Parkinson disease. Susceptibility to pesticides may be modified by genetic variants of xenobiotic enzymes, such as paraoxonase, that play a role in metabolizing some organophosphates.
We examined associations between Parkinson disease and the organophosphates diazinon, chlorpyrifos, and parathion, and the influence of a functional polymorphism at position 55 in the coding region of the PON1 gene (PON1-55). From 1 January 2001 through 1 January 2008, we recruited 351 incident cases and 363 controls from three rural California counties in a population-based case-control study. Participants provided a DNA sample, and residential exposure to organophosphates was determined from pesticide usage reports and a geographic information system (GIS) approach. We assessed the main effects of both genes and pesticides in unconditional logistic regression analyses, and evaluated the effect of carrying a PON1-55 MM variant on estimates of effects for diazinon, chlorpyrifos, and parathion exposures.
Carriers of the variant MM PON1-55 genotype exposed to organophosphates exhibited a greater than 2-fold increase in Parkinson disease risk compared with persons who had the wildtype or heterozygous genotype and no exposure (for diazinon, odds ratio = 2.2 [95% confidence interval = 1.1–4.5]; for chlorpyrifos, 2.6 [1.3–5.4]). The effect estimate for chlorpyrifos, was more pronounced in younger-onset cases and controls (≤60 years) (5.3 [1.7–16]). No increase in risk was noted for parathion.
The increase in risk we observed among PON1-55 variant carriers for specific organophosphates metabolized by PON1 underscores the importance of considering susceptibility factors when studying environmental exposures in Parkinson disease.
Life expectancy, or the estimated average age of death, is among the most basic measures of a population's health. However, monitoring differences in life expectancy among sociodemographically defined populations has been challenging, at least in the United States (US), because death certification does not include collection of markers of socioeconomic status (SES). In order to understand how SES and race/ethnicity independently and jointly affected overall health in a contemporary US population, we assigned a small area-based measure of SES to all 689,036 deaths occurring in California during a three-year period (1999-2001) overlapping the most recent US census. Residence at death was geocoded to the smallest census area available (block group) and assigned to a quintile of a multifactorial SES index. We constructed life tables using mortality rates calculated by age, sex, race/ethnicity and neighborhood SES quintile, and produced corresponding life expectancy estimates. We found a 19.6 (±0.6) year gap in life expectancy between the sociodemographic groups with the longest life expectancy (highest SES quintile of Asian females; 84.9 years) and the shortest (lowest SES quintile of African-American males; 65.3 years). A positive SES gradient in life expectancy was observed among whites and African-Americans but not Hispanics or Asians. Age-specific mortality disparities varied among groups. Race/ethnicity and neighborhood SES had substantial and independent influences on life expectancy, underscoring the importance of monitoring health outcomes simultaneously by these factors. African-American males living in the poorest 20% of California neighborhoods had life expectancy comparable to that reported for males living in developing countries. Neighborhood SES represents a readily available metric for ongoing surveillance of health disparities in the US.
racial disparities; social class disparities; life expectancy; California; population-based; USA; socioeconomic status (SES)
We estimated trends in breast cancer incidence rates for specific Asian populations in California to determine if disparities exist by immigrant status and age.
To calculate rates by ethnicity and immigrant status, we obtained data for 1998 through 2004 cancer diagnoses from the California Cancer Registry and imputed immigrant status from Social Security Numbers for the 26% of cases with missing birthplace information. Population estimates were obtained from the 1990 and 2000 US Censuses.
Breast cancer rates were higher among US- than among foreign-born Chinese (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] = 1.72, 1.96) and Filipina women (IRR = 1.32; 95% CI=1.20, 1.44), but similar between US- and foreign-born Japanese women. US-born Chinese and Filipina women who were younger than 55 years had higher rates than did White women of the same age. Rates increased over time in most groups, as high as 4% per year among foreign-born Korean and US-born Filipina women. From 2000–2004, the rate among US-born Filipina women exceeded that of White women.
These findings challenge the notion that breast cancer rates are uniformly low across Asians and therefore suggest a need for increased awareness, targeted cancer control, and research to better understand underlying factors.
Neuropeptide Y (NPY) interacts with the Y1 receptor, NPY1R, to control adrenergic activity and BP. We asked whether naturally occurring genetic variation at the human NPY1R locus alters autonomic traits that might predispose individuals to cardiovascular disease.
Methods and Results:
We identified polymorphisms in NPY1R by resequencing the gene in ethnically diverse people. 376 twins/siblings were evaluated for heritable autonomic traits: baroreflex function and pressor response to stress. Common NPY1R variant A+1050G in the 3′-untranslated region (3′-UTR) predicted baroreceptor (p=0.014-0.047) and BP change to environmental (cold) stress (p=0.0091-0.016), with minor allele homozygotes displaying blunted baroreceptor function and exaggerated pressor responses. In 936 individuals with the most extreme BPs in the population, not only 3′-UTR A+1050G (p=1.2E-4) but also promoter A-585T (p=0.001) affected both SBP and DBP, in interactive fashion (p=0.007), with combined homozygotes showing the highest DBP (>20 mmHg). 3′-UTR variant +1050G decreased reporter expression by a transfected luciferase reporter/NPY1R 3′-UTR expression plasmid, while promoter variant A-585 also decreased expression by an NPY1R promoter/luciferase reporter. Thus, the alleles that increased BP in vivo (3′-UTR +1050G, promoter A-585) also decreased NPY1R expression in cella. Computational alignment showed that A+1050G disrupted a microRNA motif.
Our results indicate that naturally occurring genetic variation at the NPY1R locus has implications for heritable autonomic control of the circulation, and ultimately for systemic hypertension. The findings suggest novel pathophysiological links between the NPY1R locus, autonomic activity and blood pressure, and suggest new strategies to approach the mechanism, diagnosis and treatment of systemic hypertension.
hypertension; neuropeptide; genetics
It is controversial whether worldwide increases in melanoma incidence represent a true epidemic. Dramatic increases in incidence in the setting of relatively stable mortality trends have also been attributed to expanded skin screening and detection of biologically indolent tumors with low metastatic potential. To better understand how melanoma incidence trends varied by severity at diagnosis and factors relevant to screening access, we assessed recent United States incidence and mortality trends by histologic type, tumor thickness and area-level socioeconomic status (SES). We obtained population-based data regarding diagnoses of invasive melanoma among non-hispanic whites from nearly 291 million person-years of observation by the Surveillance Epidemiology and End Results (SEER) program (1992–2004). Age-adjusted incidence and mortality rates were calculated for SEER and a subset (California) for which small-area SES measure was available. Overall, melanoma incidence increased at 3.1% (p<0.001) per year. Statistically significant rises occurred for tumors of all histologic subtypes and thicknesses, including those >4mm. Melanoma incidence rates doubled in all SES groups over a 10-year period while melanoma mortality rates did not increase significantly. We conclude that screening-associated diagnosis of thinner melanomas cannot explain the increasing rates of thicker melanomas among low SES populations with poorer access to screening.
Evidence from animal and cell models suggests that pesticides cause a neurodegenerative process leading to Parkinson's disease (PD). Human data are insufficient to support this claim for any specific pesticide, largely because of challenges in exposure assessment. The authors developed and validated an exposure assessment tool based on geographic information systems that integrated information from California Pesticide Use Reports and land-use maps to estimate historical exposure to agricultural pesticides in the residential environment. In 1998–2007, the authors enrolled 368 incident PD cases and 341 population controls from the Central Valley of California in a case-control study. They generated estimates for maneb and paraquat exposures incurred between 1974 and 1999. Exposure to both pesticides within 500 m of the home increased PD risk by 75% (95% confidence interval (CI): 1.13, 2.73). Persons aged ≤60 years at the time of diagnosis were at much higher risk when exposed to either maneb or paraquat alone (odds ratio = 2.27, 95% CI: 0.91, 5.70) or to both pesticides in combination (odds ratio = 4.17, 95% CI: 1.15, 15.16) in 1974–1989. This study provides evidence that exposure to a combination of maneb and paraquat increases PD risk, particularly in younger subjects and/or when exposure occurs at younger ages.
case-control studies; fungicides, industrial; geographic information systems; herbicides; maneb; paraquat; Parkinson disease; pesticides
Pancreatic cancer is the fourth leading cause of cancer death in the United States. Prognostic biomarkers are lacking, and treatment has limited effect on survival. Tissues from Surveillance, Epidemiology, and End Results registries (Iowa, Hawaii, and Los Angeles) were used to build a tissue microarray of 161 pancreatic tumors (113 resections and 48 biopsies). Proportional hazard models adjusted for age, race, sex, stage, time-period of diagnosis, and treatment. Associations were examined between markers (MUC1, MUC2, MUC5AC, synaptophysin, chromogranin, neuron specific enolase, epidermal growth factor receptor, HER2, CD5, CD138, CK5/6, CK19, CK20, and p53) and survival time from diagnosis. After adjusting for covariates, borderline statistically significant associations were seen between expression of each of the three mucins (MUC1, MUC2, and MUC5AC) and shorter survival time. The associations strengthened for 154 (96%) adenocarcinomas, particularly the 120 (75%) well-differentiated to moderately differentiated ductal adenocarcinomas, a tumor type that occurred more often in the cohort among White cases than cases of other racial origin (P < 0.01). For differentiated ductal adenocarcinomas, associations with shorter survival time were seen for expression of all three mucins combined versus other mucin expression patterns (adjusted hazard ratio, 1.8; 95% confidence interval, 1.2–2.6) and for MUC2(+) versus MUC2(−) expression (adjusted hazard ratio, 1.6; 95% confidence interval, 1.1–2.4). Mucin gene expression, particularly MUC2 expression, may have prognostic value for differentiated adenocarcinomas. Tumor histologies differed in this and Japanese cohorts. The tissue microarray is available to evaluate other biomarkers. Tissue-based surveillance can be used to monitor tumor histology in populations and facilitate applied research.
Investigators have hypothesized that consuming pesticide-contaminated well water plays a role in Parkinson’s disease (PD), and several previous epidemiologic studies support this hypothesis.
We investigated whether consuming water from private wells located in areas with documented historical pesticide use was associated with an increased risk of PD.
We employed a geographic information system (GIS)–based model to estimate potential well-water contamination from agricultural pesticides among 368 cases and 341 population controls enrolled in the Parkinson’s Environment and Genes Study (PEG). We separately examined 6 pesticides (diazinon, chlorpyrifos, propargite, paraquat, dimethoate, and methomyl) from among 26 chemicals selected for their potential to pollute groundwater or for their interest in PD, and because at least 10% of our population was exposed to them.
Cases were more likely to have consumed private well water and to have consumed it on average 4.3 years longer than controls (p = 0.02). High levels of possible well-water contamination with methomyl [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.00–2.78]), chlorpyrifos (OR = 1.87; 95% CI, 1.05–3.31), and propargite (OR = 1.92; 95% CI, 1.15–3.20) resulted in approximately 70–90% increases in relative risk of PD. Adjusting for ambient pesticide exposures only slightly attenuated these increases. Exposure to a higher number of water-soluble pesticides and organophosphate pesticides also increased the relative risk of PD.
Our study, the first to use agricultural pesticide application records, adds evidence that consuming well water presumably contaminated with pesticides may play a role in the etiology of PD.
agriculture; contamination; Parkinson’s; pesticide; well water
Determination whether common variation at the CHGA locus increases susceptibility to hypertension.
Chromogranin A (CHGA) regulates catecholamine storage and release. Previously we systematically identified genetic variants across CHGA.
Dense genotyping across the CHGA locus in >1000 individuals with the most extreme BPs in the population, as well twin pairs with autonomic phenotypes. Characterizing function of a trait-associated 3'-UTR variant with transfected CHGA 3'-UTR/luciferase reporter plasmids.
CHGA was overexpressed in patients with hypertension, especially hypertensive men, and CHGA predicted catecholamines. In individuals with extreme BPs, CHGA genetic variants predicted BP, especially in men, with a peak association occurred in the 3'-UTR at C+87T, accounting for up to ~12/~9 mmHg. The C+87T genotype predicted CHGA secretion in vivo, with the +87T allele (associated with lower BP) also diminishing plasma CHGA by ~10%. The C+87T 3'-UTR variant also predicted the BP response to environmental (cold) stress; the same allele (+87T) that diminished basal BP in the population also decreased the SBP response to stress by ~12 mmHg, and the response was smaller in women (by ~6 mmHg). In a chromaffin cell-transfected CHGA 3'-UTR/luciferase reporter plasmid, the +87T allele associated with lower BP also decreased reporter expression by ~30%. In cultured chromaffin cells, reducing endogenous Chga expression by si-RNA caused ~2/3 depletion of catecholamine storage vesicles.
Common variant C+87T in the CHGA 3'-UTR is a functional polymorphism causally associated with hypertension especially in men of the population, and propose steps ("intermediate phenotypes") whereby in sex-dependent fashion this genetic variant influences the ultimate disease trait. These observations suggest new molecular strategies to probe the pathophysiology, risk, and rational treatment of hypertension.
hypertension; chromaffin; catecholamine; adrenal; sympathetic