Skip to main content
. 2015 Jun 13;107(9):djv160. doi: 10.1093/jnci/djv160

Table 1.

Summary of the three-step candidate-pathway gene-environment interaction approach*

Analysis step Interaction of interest Variable of interest Model Specific procedures Product
Colon cancer risk analysis steps
Step 1: Summarize gene effects SNP-set interaction within gene SNPs on each gene separately Logic regression with logit link Cross-validation to determine optimal model size Gene-specific trees
Step 2: Summarize pathway effects Gene-gene interaction within pathway All GSTs on the pathway Logic regression with logit link Cross-validation to determine optimal model size Pathway trees
Step 3: Test gene- environment interaction Gene-environment interaction within pathway a. Subpathway- specific GSTxEb. Full pathway GSTxE Logistic regression model† Statistical significance testing Pathway GEIs
Colon cancer survival analysis steps
Step 1: Summarize gene effects SNP-set interaction within gene SNPs on each gene separately Logic regression fitting exponential survival models Cross-validation to determine optimal model size Gene-specific trees
Step 2: Summarize pathway effects Gene-gene interaction within pathway All GSTs on the pathway Logic regression fitting exponential survival models Cross-validation to determine optimal model size Pathway trees
Step 3: Test gene- environment interaction Gene-environment interaction within pathway a. Subpathway- specific GSTxEb. Full pathway GSTxE Cox proportional hazards model‡ Statistical significance testing Pathway GEIs

* GEI = gene-environment interaction; GST = gene-specific tree; GSTxE = gene-specific tree–environment interaction; SNP = single nucleotide polymorphism.

† Models adjusted for age, sex, race, study center, and pathway tree.

‡ Models adjusted for age, sex, race, study center, and pathway trees, stratified by cancer stage.