Table 1.

Summary of the 3-step candidate pathway gene-environment interaction approach.

Analysis Step	Interaction of Interest	Variable of Interest	Model	Specific Procedures	Product
Step 1: Summarize gene effects	SNP-set interaction within gene	SNPs on each gene separately	Logic regression with logit link/fitting exponential survival models	Cross-validation to determine optimal model size	Gene-specific trees (GSTs)
Step 2: Summarize pathway effects	Gene-set interaction within pathway	All GSTs on the pathway	Logic regression with logit link/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. Sub-pathway specific GSTxE * b. Full pathway GSTxE *,§	Logistic regression model §/Cox Proportional Hazards model ¥	Statistical significance testing	Pathway GEIs

* GSTxE, gene-specific tree—environment interaction; ^§ Models adjusted for age, sex, race, study center, pathway trees; ^¥ Models adjusted for age, sex, race, study center, pathway tree, stratified by cancer stage.