Background-Genetic variation plays an important role in the development of non-small cell lung cancer (NSCLC). However, major genetic factors for lung cancer have not been fully identified, especially in Chinese populations, which deters us from using a polygenic risk score (PRS) to identify sub-populations at high-risk of lung cancer for prevention.Methods-To systematically identify genetic variants for NSCLC risk, we newly genotyped 19,546 samples and conducted a meta-analysis of genome-wide association studies (GWASs) of Dai et al.

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.

Accurate imaging of glutathione (GSH) in vivo is able to provide real-time visualization of physiological and pathological conditions. Herein, we successfully synthesize bimetallic oxide MnMoO nanorods as an intelligent nanoprobe for in vivo GSH detection via photoacoustic (PA) imaging. The obtained MnMoO nanoprobe with no near-infrared (NIR) absorption in the absence of GSH would exhibit strong GSH-responsive NIR absorbance, endowing PA imaging detection of GSH. Due to the up-regulated GSH concentration in the tumor microenvironment, our MnMoO nanoprobe could be utilized for in vivo tumor-specific PA imaging. Moreover, MnMoO nanorods with GSH-responsive NIR absorbance could also be employed to achieve tumor-specific photothermal therapy (PTT). Importantly, such MnMoO nanorods show inherent biodegradability and could be rapidly cleared out from the body, minimizing their long-term body retention and potential toxicity. Our work presents a new type of GSH-responsive nanoprobe based on bimetallic oxide nanostructures, promising for tumor-specific imaging and therapy.

We newly genotyped 6,483 cases and 5,488 controls using the Illumina Global Screening Array (GSA), which included two studies (East-GWAS: 4,872 cases and 3,397 controls from Jiangsu province and Shanghai; North-GWAS: 1,611 cases and 2,091 controls from Shandong province, Hebei province and Tianjin). We consecutively recruited histopathologically confirmed gastric cancer cases from hospitals. Cancer-free controls were selected from individuals receiving routine physical examination at hospitals or those participating in community screening for non-communicable diseases. Demographic characteristics of all participants were displayed in Table S1. Onco-GWAS:Histopathologically confirmed gastric cancer cases were consecutively recruited from hospitals in Jiangsu province, China. The cancer-free control subjects were selected from individuals receiving routine physical examination at hospitals or those participating in community screening for non-communicable diseases in Jiangsu province. A total of 1,140 cases and 345 controls were genotyped using the Illumina OncoArray, and 708 controls were genotyped using the Illumina OmniZhongHua chips (Table S1). Detailed study design and genotype calling was provided previously. 1 NJ-GWAS and BJ-GWAS:For the NJ-GWAS and BJ-GWAS, individuals were derived from separate casecontrol studies conducted in Nanjing (565 cases and 1,162 controls) and Beijing (468 cases and 1,123 controls) (Table S1). Individuals were genotyped using the Affymetrix Genome-Wide Human SNP Array (V.6.0), which consisting ~ 900,000 markers. The details of study design and relevant data were reported previously. 2 1.4 SX-GWAS: A total of 1625 gastric cancer cases and 2100 controls were from the Shanxi Upper Gastrointestinal Cancer Genetics Project and the Linxian Nutrition Intervention Trial (Table S1). All participants were genotyped using the Illumina 660W Quad chip. The study was reported elsewhere 3 and the genotype data was downloaded from dbGap (study accession: phs00361.v1.p1). Quality control.The same protocol of quality control procedures on genotyping data was applied for all six GWAS datasets. The genotyped variants were excluded if they had a call rate of <95%, a P value for Hardy-Weinberg Equilibrium (HWE) in controls ≤1.0×10 −6 or a minor allele frequency (MAF) of <1% in controls; and samples were removed if they were with call rates of <95%, outliers (>6 s.d. from the mean) in population stratification analysis and heterozygosity analysis, or duplicated or related individuals (PI_HAT > 0.25).A total of 100,641 samples in the CKB cohort were genotyped with a customized Affymetrix Axiom® CKB array. Samples with call rate < 98% or gender discrepancy, or samples with extreme heterozygosity (F statistic S.D. score <5) were excluded. Variants with call rate <95% were excluded. Variants with call rate ≥ 95% and < 98%, or deviation from the expected frequency as observed in the 1000 Genomes project (the Phase III integrated variant set release, 504 East Asians), or deviation from Hardy-Weinberg disequil...