471 research outputs found

    Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

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    Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. IMPACT: These findings can guide potential prevention treatments

    Measurement of the top-quark mass using a leptonic invariant mass in pp collisions at s√ = 13 TeV with the ATLAS detector

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    A measurement of the top-quark mass (mt) in the ttÂŻ → lepton + jets channel is presented, with an experimental technique which exploits semileptonic decays of b-hadrons produced in the top-quark decay chain. The distribution of the invariant mass mâ„“ÎŒ of the lepton, ℓ (with ℓ = e, ÎŒ), from the W-boson decay and the muon, ÎŒ, originating from the b-hadron decay is reconstructed, and a binned-template profile likelihood fit is performed to extract mt. The measurement is based on data corresponding to an integrated luminosity of 36.1 fb−1 of s√ = 13 TeV pp collisions provided by the Large Hadron Collider and recorded by the ATLAS detector. The measured value of the top-quark mass is mt = 174.41 ± 0.39 (stat.) ± 0.66 (syst.) ± 0.25 (recoil) GeV, where the third uncertainty arises from changing the PYTHIA8 parton shower gluon-recoil scheme, used in top-quark decays, to a recently developed setup

    Whole-genome sequencing reveals host factors underlying critical COVID-19