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- Gao, Y, et al.
(författare)
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Leisure Sedentary Behavior and Risk of Lung Cancer: A Two-Sample Mendelian Randomization Study and Mediation Analysis
- 2021
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Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 12, s. 763626-
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Tidskriftsartikel (refereegranskat)abstract
- Leisure sedentary behavior, especially television watching, has been previously reported as associated with the risk of lung cancer in observational studies. This study aims to evaluate the causal association with two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms associated with leisure television watching, computer use, and driving were extracted from genome-wide association studies. Summary-level results of lung cancer overall and histological types were obtained from International Lung Cancer Consortium (ILCCO). In univariable MR using inverse-variance-weighted method, we observed causal effects of television watching on lung cancer [OR, 1.89, 95% confidence interval (CI), 1.41, 2.54; p = 2.33 × 10−5], and squamous cell lung cancer (OR, 2.37, 95% CI, 1.58, 3.55; p = 3.02 × 10−5), but not on lung adenocarcinoma (OR, 1.40, 95% CI, 0.94, 2.09; p = 0.100). No causal effects of computer use and driving on lung cancer were observed. Television watching significantly increased the exposure to several common risk factors of lung cancer. The associations of television watching with lung cancer and squamous cell lung cancer were compromised after adjusting for smoking quantity with multivariable MR. Our mediation analyses estimated indirect effects of television watching on lung cancer (beta, 0.31, 95% CI, 0.13, 0.52; p = 6.64 × 10−4) and squamous cell lung cancer (beta, 0.33, 95% CI, 0.14, 0.53, p = 4.76 × 10−4) mediated by smoking quantity. Our findings indicate that television watching is positively correlated with the risk of lung cancer, potentially mediated through affecting smoking quantity.
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- He, YQ, et al.
(författare)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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- Ji, Q, et al.
(författare)
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Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1211-
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Tidskriftsartikel (refereegranskat)abstract
- Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor–stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.
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