RESUMO
BACKGROUND: The Melanocortin 1 Receptor (MC1R) contributes to pigmentation, an important risk factor for developing melanoma. Evaluating SNPs in MC1R and association with race/ethnicity, skin type, and perceived cancer risk in a New Mexico (NM) population will elucidate the role of MC1R in a multicultural population. METHODS: We genotyped MC1R in 191 NMs attending a primary care clinic in Albuquerque. We obtained individuals' self-identified race/ethnicity, skin type, and perceived cancer risk. We defined genetic risk as carriage of any one or more of the nine most common SNPs in MC1R. RESULTS: We found that one MC1R SNP, R163Q (rs885479), was identified in 47.6% of self-identified Hispanics and 12.9% of non-Hispanic whites (NHW), making Hispanics at higher "genetic risk" (as defined by carrying one of the MC1R common variants). When we deleted R163Q from analyses, Hispanics were no longer at higher genetic risk (33.3%) compared with NHW (48.3%), consistent with melanoma rates, tanning ability, and lower perceived risk. Hispanics had a perceived risk significantly lower than NHW and a nonsignificant better tanning ability than NHW. CONCLUSIONS: The R163Q variant in MC1R may not be a risk factor for melanoma among NM Hispanics. This suggestion points to the need to carefully interpret genetic risk factors among specific populations. IMPACT: Genetic risk cannot be extrapolated from Northern European populations directly to non-European populations.
Assuntos
Receptor Tipo 1 de Melanocortina/genética , Variação Genética , Genótipo , Humanos , New MexicoRESUMO
We examined the relationship between continental-level genetic ancestry and racial and ethnic identity in an admixed population in New Mexico with the goal of increasing our understanding of how racial and ethnic identity influence genetic substructure in admixed populations. Our sample consists of 98 New Mexicans who self-identified as Hispanic or Latino (NM-HL) and who further categorized themselves by race and ethnic subgroup membership. The genetic data consist of 270 newly-published autosomal microsatellites from the NM-HL sample and previously published data from 57 globally distributed populations, including 13 admixed samples from Central and South America. For these data, we 1) summarized the major axes of genetic variation using principal component analyses, 2) performed tests of Hardy Weinberg equilibrium, 3) compared empirical genetic ancestry distributions to those predicted under a model of admixture that lacked substructure, 4) tested the hypotheses that individuals in each sample had 100%, 0%, and the sample-mean percentage of African, European, and Native American ancestry. We found that most NM-HL identify themselves and their parents as belonging to one of two groups, conforming to a region-specific narrative that distinguishes recent immigrants from Mexico from individuals whose families have resided in New Mexico for generations and who emphasize their Spanish heritage. The "Spanish" group had significantly lower Native American ancestry and higher European ancestry than the "Mexican" group. Positive FIS values, PCA plots, and heterogeneous ancestry distributions suggest that most Central and South America admixed samples also contain substructure, and that this substructure may be related to variation in social identity. Genetic substructure appears to be common in admixed populations in the Americas and may confound attempts to identify disease-causing genes and to understand the social causes of variation in health outcomes and social inequality.
Assuntos
Etnicidade/genética , Grupos Populacionais/genética , Identificação Social , Feminino , Humanos , América Latina , Masculino , Repetições de Microssatélites/genética , New Mexico , Análise de Componente PrincipalAssuntos
Comportamento de Redução do Risco , População Rural , Neoplasias Cutâneas/etnologia , População Branca , Estudos Transversais , Feminino , Humanos , Indígenas Norte-Americanos , Masculino , Pessoa de Meia-Idade , New Mexico/epidemiologia , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/psicologiaRESUMO
Cases of cutaneous melanoma and controls were enrolled in a New Mexico population-based study; subjects were administered questionnaires concerning ultraviolet (UV) and inorganic arsenic (iAs) exposure. Historical iAs exposure was estimated. UV exposure estimates were also derived using geospatial methods. Drinking water samples were collected for iAs analysis. Blood samples were collected for DNA repair (Comet) and DNA repair gene polymorphism assays. Arsenic concentrations were determined in urine and toenail samples. UV exposures during the previous 90 days did not vary significantly between cases and controls. Mean (±SD) current home iAs drinking water was not significantly different for cases and controls [3.98 µg/L (±3.67) vs. 3.47 µg/L (±2.40)]. iAs exposure showed no effect on DNA repair or association with melanoma. Results did not corroborate a previously reported association between toenail As and melanoma risk. Arsenic biomarkers in urine and toenail were highly significantly correlated with iAs in drinking water. A UV-DNA repair interaction for UV exposure over the previous 7-90 days was shown; cases had higher DNA damage than controls at low UV values. This novel finding suggests that melanoma cases may be more sensitive to low-level UV exposure than are controls. A UV-APEX1 interaction was shown. Subjects with the homozygous rare APEX1 DNA repair gene allele had a higher risk of early melanoma diagnosis at low UV exposure compared with those with the homozygous wild type or the heterozygote. Notably, a UV-arsenic interaction on inhibition of DNA repair was not observed at iAs drinking water concentrations below 10 ppb (µg/L).
Assuntos
Arsênio/análise , Arsênio/toxicidade , Cocarcinogênese , Melanoma/epidemiologia , Raios Ultravioleta/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Arsênio/urina , Estudos de Casos e Controles , Reparo do DNA , Água Potável/análise , Feminino , Humanos , Masculino , Melanoma/etiologia , Pessoa de Meia-Idade , Unhas/química , New Mexico , Neoplasias Cutâneas , Vitamina D/sangue , População Branca , Melanoma Maligno CutâneoRESUMO
Chronic exposure to urban traffic pollution is documented to promote atherosclerosis in adults but little is known about its potential effects in children. Our study examined the association of long-term exposure to traffic with carotid intima-media thickness (cIMT) in 287 healthy children. Residential proximity and distance-weighted traffic density (DWTD) were used as proximity markers for traffic-related air pollution exposure. The multivariable analyses revealed that children residing <100 meters from the nearest heavily trafficked road had cIMT mean and maximum measurements that were increased by 15% and 11% compared to those living ≥ 200 meters away (P = 0.0001). Similar increases in cIMT were identified for children in the highest versus lowest DWTD tertile. Children who resided 100-199 meters from traffic or in the middle DWTD tertile also exhibited increased cIMT but these differences were not statistically significant. No statistically significant differences were identified between residential distance to traffic or DWTD and systemic inflammation indicators (CRP, IL-6). The study results suggest that exposure to urban traffic promotes arterial remodeling in children. This finding is important since even small increases in cIMT over time can potentially lead to earlier progression to atherosclerosis. It is also important because traffic-related pollution is potentially modifiable.
Assuntos
Poluentes Atmosféricos/toxicidade , Proteína C-Reativa/metabolismo , Artérias Carótidas/efeitos dos fármacos , Espessura Intima-Media Carotídea , Exposição Ambiental , Inflamação/epidemiologia , Interleucina-6/sangue , Emissões de Veículos/toxicidade , Poluentes Atmosféricos/análise , Espessura Intima-Media Carotídea/estatística & dados numéricos , Criança , Equador/epidemiologia , Feminino , Humanos , Inflamação/induzido quimicamente , Masculino , Emissões de Veículos/análiseRESUMO
OBJECTIVES: A cross-sectional epidemiological study explored genetic susceptibility to oral precancer and cancer in Puerto Rico (PR). MATERIALS AND METHODS: Three hundred three individuals with a benign oral condition, oral precancer (oral epithelial hyperplasia/hyperkeratosis, oral epithelial dysplasia), or oral squamous cell carcinoma (SCCA) were identified via PR pathology laboratories. A standardized, structured questionnaire obtained information on epidemiological variables; buccal cells were collected for genetic analysis. Genotyping was performed using Taqman® assays. Allelic frequencies of single nucleotide polymorphisms (SNPs) were evaluated in cytokine genes and genes influencing tumor metastasis. Risk estimates for a diagnosis of oral precancer or SCCA while having a variant allele were generated using logistic regression. Adjusted models controlled for age, gender, ancestry, education, smoking and alcohol consumption. RESULTS: Relative to persons with a benign oral lesion, individuals with homozygous recessive allelic variants of tumor necrosis factor (TNF-α) -238 A/G SNP had a reduced odds of having an oral precancer (ORadjustedâ=â0.15; 95% CI 0.03-0.70). The transforming growth factor beta-1 (TGFß-1 -509 C/T) polymorphism was inversely associated with having an oral SCCA among persons homozygous for the recessive variant (ORcrudeâ=â0.27; 95% CI 0.09-0.79). The matrix metalloproteinase gene (MMP-1) variant, rs5854, was associated with oral SCCA; participants with even one variant allele were more likely to have oral SCCA (ORadjustedâ=â2.62, 95% CI 1.05-6.53) compared to people with ancestral alleles. CONCLUSION: Our exploratory analyses suggest that genetic alterations in immune system genes and genes with metastatic potential are associated with oral precancer and SCCA risk in PR.
Assuntos
Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Adulto , Idoso , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interleucina-10/genética , Interleucina-1beta/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Polimorfismo de Nucleotídeo Único/genética , Porto RicoRESUMO
BACKGROUND: Hispanics are known to be an extremely diverse and genetically admixed ethnic group. The lack of methodologies to control for ethnicity and the unknown admixture in complex study populations of Hispanics has left a gap in understanding certain cancer disparity issues. Incidence rates for oral and pharyngeal cancer (OPC) in Puerto Rico are among the highest in the Western Hemisphere. We conducted an epidemiological study to examine risk and protective factors, in addition to possible genetic susceptibility components, for oral cancer and precancer in Puerto Rico. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 310 Puerto Rico residents who had been diagnosed with either an incident oral squamous cell carcinoma, oral precancer, or benign oral condition. Participants completed an in-person interview and contributed buccal cells for DNA extraction. ABI Biosystem Taqman™ primer sets were used for genotyping 12 ancestry informative markers (AIMs). Ancestral group estimates were generated using maximum likelihood estimation software (LEADMIX), and additional principal component analysis was carried out to detect population substructures. We used unconditional logistic regression to assess the contribution of ancestry to the risk of being diagnosed with either an oral cancer or precancer while controlling for other potential confounders. The maximum likelihood estimates showed that study participants had a group average ancestry contribution of 69.9% European, 24.5% African, and 5.7% detectable Native American. The African and Indigenous American group estimates were significantly higher than anticipated. Neither self-identified ethnicity nor ancestry markers showed any significant associations with oral cancer/precancer risk in our study. CONCLUSIONS/SIGNIFICANCE: The application of ancestry informative markers (AIMs), specifically designed for Hispanics, suggests no hidden population substructure is present based on our sampling and provides a viable approach for the evaluation and control of ancestry in future studies involving Hispanic populations.
Assuntos
Neoplasias Bucais/etnologia , Neoplasias Bucais/genética , Filogenia , Lesões Pré-Cancerosas/etnologia , Lesões Pré-Cancerosas/genética , Autorrelato , Adulto , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Porto Rico/etnologiaRESUMO
Among New Mexican Hispanic women, breast cancer is detected at a more advanced stage than compared to Non-Hispanic White women. One central factor that has been little studied is the role of critical cytokines. We genotyped incident breast cancer cases and their age-, gender- and smoking-matched controls (N=40 matched pairs) for 25 single nucleotide polymorphisms (SNPs) in cytokine genes. We measured corresponding serum cytokine levels as well. Five cytokines (IL-1beta, IL-5, TNF-alpha, IL-6 and IL-2) were significantly associated with disease and based on their serum levels, concentrations were higher in the cases than in the controls. Disease odds ratios corresponding to one standard deviation change in log-transformed concentrations of these cytokines were 18.87, 4.10, 3.61, 3.27 and 2.52. Three most statistically significant SNPs were rs2069705, located in the promoter region of the interferon gamma gene (INF-gamma); rs2243248, in the promoter of IL-4 (rs2243248); and rs1800925, in the promoter of the IL-13 gene. Increased serum cytokine levels at diagnosis are indicative for immunological alterations and possibly related to genetic susceptibility markers as well. These findings might guide us to understand the presence of SNPs in cytokine genes and serum concentrations among breast cancer patients and potentially in other cancers.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Citocinas/sangue , Citocinas/genética , Polimorfismo Genético , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , New Mexico , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Particulate matter less than 10 microm (PM10) has been shown to be associated with aggravation of asthma and respiratory and cardiopulmonary morbidity. There is also great interest in the potential health effects of PM2.5. Particulate matter (PM) varies in composition both spatially and temporally depending on the source, location and seasonal condition. El Paso County which lies in the Paso del Norte airshed is a unique location to study ambient air pollution due to three major points: the geological land formation, the relatively large population and the various sources of PM. In this study, dichotomous filters were collected from various sites in El Paso County every 7 days for a period of 1 year. The sampling sites were both distant and near border crossings, which are near heavily populated areas with high traffic volume. Fine (PM2.5) and Coarse (PM10-2.5) PM filter samples were extracted using dichloromethane and were assessed for biologic activity and polycyclic aromatic (PAH) content. Three sets of marker genes human BEAS2B bronchial epithelial cells were utilized to assess the effects of airborne PAHs on biologic activities associated with specific biological pathways associated with airway diseases. These pathways included in inflammatory cytokine production (IL-6, IL-8), oxidative stress (HMOX-1, NQO-1, ALDH3A1, AKR1C1), and aryl hydrocarbon receptor (AhR)-dependent signaling (CYP1A1). Results demonstrated interesting temporal and spatial patterns of gene induction for all pathways, particularly those associated with oxidative stress, and significant differences in the PAHs detected in the PM10-2.5 and PM2.5 fractions. Temporally, the greatest effects on gene induction were observed in winter months, which appeared to correlate with inversions that are common in the air basin. Spatially, the greatest gene expression increases were seen in extracts collected from the central most areas of El Paso which are also closest to highways and border crossings.