We determined the association between charred meat consumption, cigarette smoking, microsomal epoxide hydrolase (mEH) polymorphisms (rs1051740 and rs2234922), and colorectal adenomas and hyperplastic polyps (HPs) and explored gene–environment interactions. Men and women with colorectal adenomas (n = 519), HPs (n = 691), or concurrently with both types of polyps (n = 227) and polyp-free controls (n = 772) receiving a colonoscopy from December 2004 to September 2007 were recruited. Participants completed telephone interviews and provided buccal cell samples; genotyping of mEH was completed using Taqman assays. We conducted polytomous regression and calculated odd ratios (OR) and 95% confidence intervals. Interactions were evaluated using Wald chi-square tests. Consumption of >3 servings of charred meat per week was associated with distal HPs (OR = 2.0, 1.2–3.4) but not adenomas nor either type of proximal polyp. Heavy cigarette smoking (≥ 22 pack-years) was associated with an increased risk for colorectal adenomas (OR = 1.7, 95% CI: 1.2–2.4), HPs (OR = 2.4, 95% CI: 1.7–3.3), and both types (OR = 2.8, 95% CI: 1.8–4.3) with the strongest association for distal polyps. There was no association between mEH genotype and colorectal polyps, nor were any statistically significant gene–environment interactions identified. Future investigation of BaP exposure and colorectal neoplasia should analyze whether associations are dependent upon anatomic location.