Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with ...inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 ...tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%) or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.
The surface topography of noble metal particles is a significant factor in tailoring surface-enhanced Raman scattering （SERS） properties. Here, we present a simple fabrication route to hexagonally ...arranged arrays of surface-roughened urchin- like Ag hemispheres （Ag-HSs） decorated with Ag nanoparticles （Ag-NPs） for highly active and reproducible SERS substrates. The urchin-like Ag-HS arrays are achieved by sputtering Ag onto the top surface of a highly ordered porous anodic aluminum oxide （AAO） template to form ordered arrays of smooth Ag-HSs and then by electrodepositing Ag-NPs onto the surface of each Ag-HS. Owing to the ordered arrangement of the Ag-HSs and the improved surface roughness, the urchin-like hierarchical Ag-HS arrays can provide sufficient and uniform ＂hot spots＂ for reproducible and highly active SERS effects. Using the urchin-like Ag-HS arrays as SERS substrates, 10-7 M dibutyl phthalate （a member of plasticizers family） and 1.5 × 10-5 M PCB-77 （one congener of polychlorinated biphenyl, a notorious class of pollutants） are identified, showing promising potential for these substrates in the rapid recognition of organic pollutants.
Based on regional geology, 2D seismic and ocean drilling data, the formation of the Eratosthenes Seamount (ESM) and its surrounding isolated platforms, types of organic reefs and hydrocarbon ...accumulation conditions in the eastern Mediterranean were analyzed through fine tectonic interpretation and seismic facies study, and the future exploration targets were pointed out. The formation and evolution of the ESM and its peripheral isolated platforms are highly related to the open and close of the Neotethyan ocean. The precursors of the ESM and its peripheral isolated platforms are both horst-type fault blocks formed in the Middle Triassic–Early Jurassic intracontinental rift stage. The ESM and its peripheral isolated platforms underwent continued and inherited carbonate build-ups during the Middle Jurassic intercontinental rift stage, the Late Jurassic–Late Cretaceous Turonian passive drift stage, and Late Cretaceous Senonian–Miocene subduction stage, as well as medium-slight inversion transformation beginning in the Late Miocene Messinian caused by the closure of the Neotethyan ocean. Three types of isolated platforms formed controlled by variant paleo-tectonic settings: the first type is composed of a single patch-like reef controlled by a small-scale and narrow horst-type fault block, the second type consists of a single atoll controlled by a middle-scale and wide horst-type fault block, and the third type is comprised of multiple reef-beach complexes controlled by a large-scale and broad paleo-high. The first two types universally developed in the highs of the alternate sag-uplift structural zones on the south and west of Eratosthenes, and the third type only developed in the ESM. As a result of fluctuation of sea level, two sequences of reef build-ups, i.e. the Middle Jurassic Bajocian–Upper Cretaceous Turonian and the Miocene, developed in the ESM as well as the highs in the alternate sag-uplift structural zones on the south and west of Eratosthenes. Drillings have confirmed that the first two types of isolated platforms with a single patch-like reef and a single circle-like reef have good conditions for natural gas accumulations. The isolated platform of reef-beach complexes in the ESM also has accumulation potentials of natural gas and is worth prospecting.
Past history of gallstones is associated with increased risk of gallbladder cancer in observational studies. We conducted complementary observational and Mendelian randomization (MR) analyses to ...determine whether history of gallstones is causally related to development of gallbladder cancer in an Indian population.
To investigate associations between history of gallstones and gallbladder cancer, we used questionnaire and imaging data from a gallbladder cancer case-control study conducted at Tata Memorial Hospital, Mumbai, Maharashtra, India (cases = 1,170; controls = 2,525). We then used 26 genetic variants identified in a genome-wide association study of 27,174 gallstone cases and 736,838 controls of European ancestry in an MR approach to assess causality. The association of these genetic variants with both gallstones and gallbladder cancer was examined in the gallbladder cancer case-control study. Various complementary MR approaches were used to evaluate the robustness of our results in the presence of pleiotropy and heterogeneity, and to consider the suitability of the selected SNPs as genetic instruments for gallstones in an Indian population.
We found a strong observational association between gallstones and gallbladder cancer using self-reported history of gallstones OR = 4.5; 95% confidence interval (CI) = 3.5-5.8 and with objective measures of gallstone presence using imaging techniques (OR = 2.0; 95% CI = 1.5-2.7). We found consistent causal estimates across all MR techniques, with ORs for gallbladder cancer in the range of 1.3-1.6.
Our findings indicate a causal relationship between history of gallstones and increased risk of gallbladder cancer, albeit of a smaller magnitude than those found in observational analysis.
Our findings emphasize the importance of gallstone treatment for preventing gallbladder cancer in high-risk individuals.
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP ...markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.
The East African Rift System (EARS) is the youngest rift with the eastern and western branches, consisting of multiple secondary rifts. It is generally characterized by low extent of exploration and ...great exploration potential. Identifying the differences in hydrocarbon accumulation conditions in various rifts is very important in providing guidance for hydrocarbon exploration and selecting favorable exploration targets in this area. Based on the interpretation of first-hand seismic-geological data, and combining other materials such as commercial databases and open access literature, the structural characteristics of the main rifts in the eastern and western branches of the EARS are comparatively analyzed; based on the anatomy of the discovered hydrocarbon reservoirs, the rifts of the EARS are classified into four types depending on their structural styles, including double-fault type, simple single-fault type, single-fault transfer type, and single-fault terrace type, and the control of structural style over hydrocarbon accumulation in the EARS is discussed. In the Western Branch of the EARS, large rifts such as the Albertine Rift and the Tanganyika Rift are mainly of double-fault type and single-fault transfer type, and only some small rifts are of the simple single-fault type. The rifts in the Eastern Branch of the EARS are generally small; the rifts in the northern section of the Western Branch are mainly of the simple single-fault type, and those in the southern section are mainly of the single-fault terrace type. The hydrocarbon potential of double-fault rifts is the greatest, followed by that of simple single-fault rifts and single-fault transfer rifts, and the hydrocarbon potential of single-fault terrace rifts is relatively limited. The results obtained from a comparative analysis of the structures, sediment fills, and reservoir elements of various rifts show that the west side of the Albertine Rift, the southeast of the Tanganyika Rift, the Kerio Rift, and the land in the northwest of the Turkana Rift have great exploration potential.
The genetic regulation of the human epigenome is not fully appreciated. Here we describe the effects of genetic variants on the DNA methylome in human lung based on methylation-quantitative trait ...loci (meQTL) analyses. We report 34,304 cis- and 585 trans-meQTLs, a genetic-epigenetic interaction of surprising magnitude, including a regulatory hotspot. These findings are replicated in both breast and kidney tissues and show distinct patterns: cis-meQTLs mostly localize to CpG sites outside of genes, promoters and CpG islands (CGIs), while trans-meQTLs are over-represented in promoter CGIs. meQTL SNPs are enriched in CTCF-binding sites, DNaseI hypersensitivity regions and histone marks. Importantly, four of the five established lung cancer risk loci in European ancestry are cis-meQTLs and, in aggregate, cis-meQTLs are enriched for lung cancer risk in a genome-wide analysis of 11,587 subjects. Thus, inherited genetic variation may affect lung carcinogenesis by regulating the human methylome.
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