Determination of the SNP-SNP Interaction between Breast Cancer Related Genes to Analyze the Disease Susceptibility

 Abstract—Investigation of the single nucleotide polymorphism (SNP)-SNP interaction model can facilitate the analysis of the susceptibility to disease. The model explains the risk of association between the genotypes and the disease in case-control study. Thus, many mathematic methods are widely applied to identify the statistically significant model such as odds ratio (OR), chi-square test, and error rate. However, a huge number of data sets have been found to limit the statistical methods to identify the significant model. In this study, we propose a novel statistical method, complementary-logic particle swarm optimization (CLPSO), to increase the efficiency of significant model identification in case-control study. The complementary-logic is implemented to improve the PSO search ability and identify a better SNP-SNP interaction model. Six important breast cancer genes including 23 SNPs and simulated huge number of data sets were selected as the test data sets. The methods of PSO and CLPSO were applied on the identification of SNP-SNP interactions in the two-way to five-way. In results, the OR evaluates the breast cancer risk of the identified SNP-SNP interaction model. Compared to the corresponding non-interaction model, if the OR value is greater than 1 that indicates the model is significant risk between cases and controls. The results showed that CLPSO is able to identify the significant models for specific SNP-SNP interaction of two-way to five-way (OR value: 1.153-1.391; confidence interval (CI): 1.05-1.79; p-value: 0.01-0.003). The model suggests that the genes ESR1, PGR, and SHBG may be an important role in the interactive effects to breast cancer. In addition, we compared the search abilities of PSO and CLPSO for identification of the significant model. Results revealed that CLPSO can identify better model with difference values between cases and controls than PSO; it suggests CLPSO can be used to identify a better SNP-SNP interaction models.

[1]  Stephen J. Chanock,et al.  Polymorphism Interaction Analysis (PIA): a method for investigating complex gene-gene interactions , 2008, BMC Bioinformatics.

[2]  Habtom W. Ressom,et al.  Analysis of mass spectral serum profiles for biomarker selection , 2005, Bioinform..

[3]  A D Roses,et al.  Complex disease-associated pharmacogenetics: drug efficacy, drug safety, and confirmation of a pathogenetic hypothesis (Alzheimer's disease) , 2007, The Pharmacogenomics Journal.

[4]  Li-Yeh Chuang,et al.  Generating SNP barcode to evaluate SNP-SNP interaction of disease by particle swarm optimization , 2009, Comput. Biol. Chem..

[5]  Yang Cheng-Hong,et al.  Odds ratio-based genetic algorithms for generating SNP barcodes of genotypes to predict disease susceptibility. , 2008 .

[6]  Li-Yeh Chuang,et al.  Chaotic particle swarm optimization for detecting SNP–SNP interactions for CXCL12-related genes in breast cancer prevention , 2012, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[7]  Li-Yeh Chuang,et al.  Novel generating protective single nucleotide polymorphism barcode for breast cancer using particle swarm optimization. , 2009, Cancer epidemiology.

[8]  I. Gray,et al.  Single nucleotide polymorphisms as tools in human genetics. , 2000, Human molecular genetics.

[9]  Charles R Cantor,et al.  The Use of Genetic SNPs as New Diagnostic Markers in Preventive Medicine , 2005, Annals of the New York Academy of Sciences.

[10]  Alison M Dunning,et al.  Association between Common Variation in 120 Candidate Genes and Breast Cancer Risk , 2007, PLoS genetics.

[11]  Hsueh-Wei Chang,et al.  Computational analysis of simulated SNP interactions between 26 growth factor-related genes in a breast cancer association study. , 2011, Omics : a journal of integrative biology.