| 1. |
- Ji, Xinyu, et al.
(författare)
-
Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC
- 2022
-
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:3, s. 717-731
-
Tidskriftsartikel (refereegranskat)abstract
- The interaction between DNA methylation of tripartite motif containing 27 (cg05293407TRIM27) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early-stage non-small-cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three-way interactions. A two-phase study was adopted to identify three-way interactions in the form of pack-year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407TRIM27 × epigenome-wide DNA methylation CpG probe. Two CpG probes were identified with FDR-q ≤ 0.05 in the discovery phase and P ≤ 0.05 in the validation phase: cg00060500KIAA0226 and cg17479956EXT2. Compared to a prediction model with only clinical information, the model added 42 significant three-way interactions using a looser criterion (discovery: FDR-q ≤ 0.10, validation: P ≤ 0.05) had substantially improved the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model for both 3-year and 5-year survival. Our research identified the complex interaction effects among multiple environment and epigenetic factors, and provided therapeutic target for NSCLC patients.
|
|
| 2. |
- Zhang, Ruyang, et al.
(författare)
-
A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians
- 2022
-
Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 17:8, s. 974-990
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).Methods: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms (SNPs). Then, the top interactions were further tested by demographically adjusted logistic regression models. Finally, we used the selected interactions to build lung cancer screening models of NSCLC, separately, for never and ever smokers.Results: With the Bonferroni correction, we identified eight statistically significant pairs of SNPs, which predominantly appeared in the 6p21.32 and 5p15.33 regions (e.g., rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.17, p = 6.57 × 10−13; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.17, p = 2.43 × 10−13; rs2858859HLA-DQA1 and rs9275572HLA-DQA2, ORinteraction = 1.15, p = 2.84 × 10−13; rs2853668TERT and rs62329694CLPTM1L, ORinteraction = 0.73, p = 2.70 × 10−13). Notably, even with much genetic heterogeneity across ethnicities, three pairs of SNPs in the 6p21.32 region identified from the European-ancestry population remained significant among an Asian population from the Nanjing Medical University Global Screening Array project (rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.13, p = 0.008; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.11, p = 5.23 × 10−4; rs3135369BTNL2 and rs9271300HLA-DQA1, ORinteraction = 0.89, p = 0.006). The interaction-empowered polygenetic risk score that integrated classical polygenetic risk score and G × G information score was remarkable in lung cancer risk stratification.Conclusions: Important G × G interactions were identified and enriched in the 5p15.33 and 6p21.32 regions, which may enhance lung cancer screening models.
|
|
