Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified. METHODS: An association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN. RESULTS: We first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10-7 for rs2517611 at 6p22.1, p=1.76×10-9 for rs2524182 at 6p21.33 and p=2.17×10-10 for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1 to the promoter of TCF19. In addition, experiments revealed that the inhibition of TCF19 may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN. CONCLUSION: These findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that TCF19 may function as a putative susceptibility gene for SCCHN.

[Comparison of pretreatment methods in lipid analysis and ultra-performance liquid chromatography-mass spectrometry analysis of archaea].

Archaea are single-cell microorganisms, structurally and biochemically similar to bacteria and fungi. Most of them live in extreme environments, such as high salt, extremely acidic, extremely hot, and anaerobicenvironments. The membrane structure and related metabolic pathways of archaea are different from those of other microorganisms. Therefore, studying the lipid metabolism of archaea is of great significance for exploring the life activities in extreme environments. As the first step in lipidomic analysis, lipid extraction and pretreatment methods play an important role, as they influence the accuracy and reliability of the final results. We harnessed ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) to detect the total normal lipids. The hyperthermophilic archaeon Pyrococcus yayanosii was selected as the model. The Bligh-Dyer acidic method, Folch method, methyl tert-butyl ether (MTBE) method, and solid-phase extraction (SPE) method were compared by multi-component analysis in terms of extraction efficiency, reproducibility, and extraction discrimination. Comprehensive analysis revealed that the SPE and MTBE methods showed the best extraction repeatability and extraction efficiency, and were suitable for high-throughput microbial lipid extraction. Finally, normal lipid components of P. yayanosii were comprehensively analyzed by SPE coupled with UPLC-HRMS. A total of 1402 lipid components were identified. This article aims to provide a reference for non-targeted lipidomic analysis of archaea and other microorganisms towards understanding their lipid metabolism.

ATG12 expression quantitative trait loci associated with head and neck squamous cell carcinoma risk in a Chinese Han population.

Autophagy is an essential process to maintain cellular homeostasis and functions, which has been demonstrated to play an important role in the different stages of tumorigenesis. To evaluate whether the genetic variants in autophagy-related genes influence the head and neck squamous cell carcinoma (HNSCC) risk, we conducted a case-control study to analyze 11 tagging single nucleotide polymorphisms (SNPs) of three core autophagosome formation genes (ATG5, ATG12, and ATG16L1) with 576 HNSCC cases and 1552 healthy controls among Chinese population. Finally, we identified that rs26537 of ATG12 (additive model: adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.03-1.37, P = 0.017) and rs4663402 in ATG16L1 (additive model: adjusted OR = 1.39, 95%CI = 1.08-1.80, P = 0.010) were significantly associated with the increased risk of HNSCC. However, no association was detected between other SNPs and HNSCC risk. The results of expression quantitative trait loci (eQTL) analysis based on Genotype-Tissue Expression (GTEx) accessible data, showed that the risk allele of rs26537 was significantly associated with up-regulated expression of ATG12 (P = 0.0021). Further luciferase activity assay indicated that rs26537 T > C in ATG12 intron one region significantly enhanced transcription activity. These results suggested that ATG12 eQTL SNP rs26537 might contribute to an allele-specific effect on the expression of host gene ATG12 and explain a fraction of HNSCC genetic susceptibility.