1. Predictive model for risk of gastric cancer using genetic variants from genome‐wide association studies and high‐evidence meta‐analysis
- Author
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Jiucun Wang, Weijian Guo, Ruoxin Zhang, Jing He, Yajun Yang, Mengyun Wang, Li-Xin Qiu, Xiaofei Qu, Xiao-Dong Zhu, Menghong Sun, and Lei Cheng
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Genome-wide association study ,Logistic regression ,susceptibility ,predictive model ,0302 clinical medicine ,Risk Factors ,immune system diseases ,skin and connective tissue diseases ,Original Research ,genome‐wide association study ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Phenotype ,030220 oncology & carcinogenesis ,Meta-analysis ,Female ,Cancer Prevention ,China ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Risk Assessment ,lcsh:RC254-282 ,03 medical and health sciences ,Meta-Analysis as Topic ,Predictive Value of Tests ,Stomach Neoplasms ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Radiology, Nuclear Medicine and imaging ,Genetic Testing ,Retrospective Studies ,Genetic association ,Models, Genetic ,Multifactor dimensionality reduction ,Receiver operating characteristic ,gastric cancer ,Reproducibility of Results ,030104 developmental biology ,Gene-Environment Interaction ,prognosis ,Genome-Wide Association Study - Abstract
Genome‐wide association studies (GWAS) have identified some single nucleotide polymorphisms (SNPs) associated with the risk of gastric cancer (GCa). However, currently, there is no published predictive model to assess the risk of GCa. In the present study, risk‐associated SNPs derived from GWAS and large meta‐analyses were selected to construct a predictive model to assess the risk of GCa. A total of 1115 GCa cases and 1172 controls from the eastern Chinese population were included. Logistic regression models were used to identify SNPs that correlated with the risk of GCa. A predictive model to assess the risk of GCa was established by receiver operating characteristic curve analysis. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) were applied to calculate the effect of high‐order gene‐environment interactions on risk of the cancer. A total of 42 SNPs were selected for further analysis. The results revealed that ASH1L rs80142782, PKLR rs3762272, PRKAA1 rs13361707, MUC1 rs4072037, PSCA rs2294008, and PLCE1 rs2274223 polymorphisms were associated with a risk of GCa. The area under curve considering both genetic factors and BMI was 3.10% higher than that of BMI alone. MDR analysis revealed that rs13361707 and rs4072307 variants and BMI had interaction effects on susceptibility to GCa, with the highest predictive accuracy (61.23%) and cross‐validation consistency (100/100). CART analysis also supported this interaction model that non‐overweight status and a six SNP panel could synergistically increase the susceptibility to GCa. The six SNP panel for predicting the risk of GCa may provide new tools for prevention of the cancer based on GWAS and large meta‐analyses derived genetic variants., We identifed a six‐SNPs panel from GWAS and large meta‐analysis for predicting risk of gastric cancer, which may provide new tools for gastric cancer prevention.
- Published
- 2020