Comprehensive Evaluation of One-Carbon Metabolism Pathway Gene Variants and Renal Cell Cancer Risk

Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer.Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes.The strongest associations with RCC risk were observed for SLC19A1 (P(min-P) = 0.03) and MTHFR (P(min-P) = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake.To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings

Cancer Pharmacogenomics and Pharmacoepidemiology: Setting a Research Agenda to Accelerate Translation

Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled “Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation” on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice

A hot old time in Dixie: characteristic cake-walk and two-step

(Published By New York Music Pub. Co.

Uso de analgésicos y ácido acetilsalicílico en un estudio multicéntrico en España Use of analgesics and aspirin in a Spanish multicenter study

Objetivo: Evaluar el consumo de paracetamol, metamizol y ácido acetilsalicílico (AAS) en un estudio multicéntrico. Pacientes y método: Se analizaron los controles de un estudio de casos y controles hospitalarios (n = 1.029) sobre cáncer vesical mediante la aplicación de una matriz de medicamentos y principios activos. El motivo de ingreso de los controles no se asociaba con el uso crónico de analgésicos. Se utilizó un modelo de regresión logística. Resultados: El uso crónico de AAS fue del 8%, el de paracetamol, del 5% y el de metamizol, del 2%. El AAS fue más usado por personas con educación secundaria o superior (odds ratio [OR] = 2,0, intervalo de confianza [IC] del 95%, 1,52-2,93). Las mujeres usaron más paracetamol (OR = 1,91; IC del 95%, 1,30-2,80) y metamizol (OR = 2,80; IC del 95%, 1,49-4,47). Los menores de 65 años usaron más metamizol. Conclusión: El uso crónico de AAS y paracetamol es bajo comparado con el de Estados Unidos o el norte de Europa, aunque es parecido al del sur de Europa. Hay diferencias en el uso de analgésicos en función de las variables sociodemográficas.Objective: To evaluate the use of acetaminophen (paracetamol), aspirin and dipyrone (metamizol) in a multicenter study. Patients and method: We analyzed the controls of a hospital-based case-control study (n = 1029) of bladder cancer using a matrix of drugs and active principles. The admission diagnosis of the study controls was not associated with chronic analgesic use. A logistic regression model was used. Results: Eight percent of the controls were regular users of aspirin, 5% regularly used acetaminophen and 2% regularly used dipyrone. Aspirin was more frequently used by subjects with at least secondary education (OR = 2.0; 95% CI, 1.52-2.93). Women more frequently used acetaminophen (OR = 1.91; 95% CI, 1.30-2.80) and dipyrone (OR = 2.80; 95% CI, 1.49-4.47). Subjects under 65 years old more frequently used dipyrone. Conclusion: Chronic use of aspirin and acetaminophen is lower than that reported in North America or northern Europe and is similar to that seen in southern Europe. Differences in the pattern of analgesic use were found among sociodemographic population groups

Polycyclic aromatic hydrocarbon exposure in household air pollution from solid fuel combustion among the female population of Xuanwei and Fuyuan counties, China

Exposure to polycyclic aromatic hydrocarbons (PAHs) from burning "smoky" (bituminous) coal has been implicated as a cause of the high lung cancer incidence in the counties of Xuanwei and Fuyuan, China. Little is known about variations in PAH exposure from throughout the region nor how fuel source and stove design affects exposure. Indoor and personal PAH exposure resulting from solid fuel combustion in Xuanwei and Fuyuan was investigated using repeated 24 h particle bound and gas-phase PAH measurements, which were collected from 163 female residents of Xuanwei and Fuyuan. 549 particle bound (283 indoor and 266 personal) and 193 gas phase (all personal) PAH measurements were collected. Mixed effect models indicated that PAH exposure was up to 6 times higher when burning smoky coal than smokeless coal and varied by up to a factor of 3 between different smoky coal geographic sources. PAH measurements from unventilated firepits were up to 5 times that of ventilated stoves. Exposure also varied between different room sizes and season of measurement. These findings indicate that PAH exposure is modulated by a variety of factors, including fuel type, coal source, and stove design. These findings may provide valuable insight into potential causes of lung cancer in the area

Heterogeneity in coal composition and implications for lung cancer risk in Xuanwei and Fuyuan counties, China

Background: Xuanwei and Fuyuan counties in Yunnan Province, China have among the highest lung cancer rates in the country. This has been associated with the domestic combustion of bituminous coal (referred to as "smoky" coal). Additionally, significant geographical variation in cancer rates among smoky coal users has been observed, suggesting heterogeneity in fuel source composition and/or combustion characteristics. Research thus far has indicated that smoky coal emits high levels of polycyclic aromatic hydrocarbons (PAHs) and contains high concentrations of fine grained crystalline quartz, however, much of this research is limited in terms of sample size and geographic scope. In order to more fully characterise geochemical and elemental compositions of smoky and smokeless coal use in Xuanwei and Fuyuan, we carried out a large exposure assessment study in households in this region. Methods: Fuel samples representing smoky and "smokeless" (anthracite, the major alternative coal type in the region) coals were collected from 137 homes in Xuanwei and Fuyuan. Rock-Eval, Leco-CS, XRF analysis and electron microscopy were used to establish hydrocarbon content (to represent volatile organic compounds), major and trace element composition and mineral composition respectively. Heterogeneity in coal characteristics between and within coal types was assessed by the Kruskal-Wallis test. Results: 145 coal samples (116 smoky and 29 smokeless coals) were analysed. Statistically significant differences between smoky and smokeless coals with regard to hydrocarbon content, sulfur, trace elements and mineral composition were observed. Of note, smoky coal contained between 5 and 15 times the amount of volatile organic matter and twice the amount of quartz (including respirable quartz) than smokeless coal. Smoky coal generally had lower levels of trace elements (plus aluminium) than smokeless coal. Significant variation was also observed between smoky coal samples from different geographical areas with regard to hydrocarbon content and elemental composition (including aluminium and silicon). Discussion: This paper has identified compositional differences between and within smoky and smokeless coals sourced from Xuanwei and Fuyuan counties. A decreased ratio of aluminium to silicon in smoky coal suggests elevated free silica, a finding consistent with observed higher levels of quartz. Elevated volatile organic matter content in smoky coal (when compared to smokeless coal) is consistent with the geochemical expectations for smoky and smokeless coals. These findings also reflect previous observations of elevated volatile compound emissions (notably PAHs) from smoky coal in the area. The observed heterogeneity in coal composition between and within coal types may provide leads to the observed heterogeneity in cancer risk observed in this area

Heterogeneity in coal composition and implications for lung cancer risk in Xuanwei and Fuyuan counties, China

Background: Xuanwei and Fuyuan counties in Yunnan Province, China have among the highest lung cancer rates in the country. This has been associated with the domestic combustion of bituminous coal (referred to as "smoky" coal). Additionally, significant geographical variation in cancer rates among smoky coal users has been observed, suggesting heterogeneity in fuel source composition and/or combustion characteristics. Research thus far has indicated that smoky coal emits high levels of polycyclic aromatic hydrocarbons (PAHs) and contains high concentrations of fine grained crystalline quartz, however, much of this research is limited in terms of sample size and geographic scope. In order to more fully characterise geochemical and elemental compositions of smoky and smokeless coal use in Xuanwei and Fuyuan, we carried out a large exposure assessment study in households in this region. Methods: Fuel samples representing smoky and "smokeless" (anthracite, the major alternative coal type in the region) coals were collected from 137 homes in Xuanwei and Fuyuan. Rock-Eval, Leco-CS, XRF analysis and electron microscopy were used to establish hydrocarbon content (to represent volatile organic compounds), major and trace element composition and mineral composition respectively. Heterogeneity in coal characteristics between and within coal types was assessed by the Kruskal-Wallis test. Results: 145 coal samples (116 smoky and 29 smokeless coals) were analysed. Statistically significant differences between smoky and smokeless coals with regard to hydrocarbon content, sulfur, trace elements and mineral composition were observed. Of note, smoky coal contained between 5 and 15 times the amount of volatile organic matter and twice the amount of quartz (including respirable quartz) than smokeless coal. Smoky coal generally had lower levels of trace elements (plus aluminium) than smokeless coal. Significant variation was also observed between smoky coal samples from different geographical areas with regard to hydrocarbon content and elemental composition (including aluminium and silicon). Discussion: This paper has identified compositional differences between and within smoky and smokeless coals sourced from Xuanwei and Fuyuan counties. A decreased ratio of aluminium to silicon in smoky coal suggests elevated free silica, a finding consistent with observed higher levels of quartz. Elevated volatile organic matter content in smoky coal (when compared to smokeless coal) is consistent with the geochemical expectations for smoky and smokeless coals. These findings also reflect previous observations of elevated volatile compound emissions (notably PAHs) from smoky coal in the area. The observed heterogeneity in coal composition between and within coal types may provide leads to the observed heterogeneity in cancer risk observed in this area