Computational protocol: Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients

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Protocol publication

[…] Seven SNPs in 4 genes (OCT2, ABCB1, ABCC2, and MATE1) were selected from the National Center for Biotechnology Information (NCBI) database. All of the SNPs satisfied the following criteria: (1) SNPs that were reported to be associated with lung cancer occurrence or development according to the results of existing research; (2) minor allele frequency (MAF) ≥5% in the Chinese Han population; and (3) tagging SNPs selected by Haploview (version 4.2 Cambridge, MA, USA) using pair-wise tagging with default settings (pair-wise r2 threshold = 0.8).All blood samples were stored at −20°C until DNA extraction. Within 2 months after the collection of blood samples, genomic DNA was isolated using a Genomic DNA Purification Kit (Promega, Madison, WI, USA) and stored at −20°C before use. Genotyping was conducted using the Sequenom Mass Array Genotype Platform (Sequenom, San Diego, CA, USA). [...] Patients were dichotomized according to the outcomes of toxicity and response. The allele frequencies of all the SNPs conforming to Hardy–Weinberg equilibrium (HWE) were analyzed with a χ2 test (P > 0.05). Sex, age, smoking status, tumor histology, clinical stage, and Eastern Cooperative Oncology Group (ECOG) performance status were considered as potential covariates for the logistic regression analysis. The call rate was defined as the percentage of successfully genotyped patients for each SNP. All analyses were performed using PLINK (version 1.07, http://www.pngu.mgh.harvard.edu/purcell/plink/) and SPSS 13.0 (SPSS Inc, Chicago, IL, USA) with three models: (1) additive model for comparing carriers of the minor allele with major allele subjects; (2) dominant model for comparing carriers of the minor allele with the major homozygous subjects; and (3) recessive model for comparing carriers of the major allele with the minor homozygous subjects. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the associations between outcomes and gene polymorphisms. A value of P < 0.05 was considered statistically significant. […]

Pipeline specifications

Software tools Haploview, PLINK, SPSS
Applications Miscellaneous, GWAS
Organisms Homo sapiens
Diseases Carcinoma, Non-Small-Cell Lung, Neoplasms, Drug-Related Side Effects and Adverse Reactions
Chemicals Adenosine Triphosphate, Nucleotides, Platinum