CYP1A1 plays an essential role in pathogenesis of head and neck cancers. Functional CYP1A1 Ile462Val and MspI single nucleotide polymorphisms (SNP) are considered to have significant effects on risk of head and neck cancers. Several case-control studies have examined how these genetic polymorphisms are involved in development of this group of malignancies, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the associations between these functional genetic variants and head and neck cancer risk. A total of 28 studies are eligible for CYP1A1 Ile462Val SNP (4639 patients and 4701 controls), and 22 studies for MspI SNP (4168 patients and 4638 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model. There was no association between Ile462Val polymorphism and head and neck cancer risk (OR = 1.23, 95% CI = 0.99-1.53, P = 0.062). However, in a stratified analysis, a statistically significant correlation between this SNP and pharyngeal cancer risk was observed (OR = 1.76, 95% CI = 1.32-2.33, P < 0.001). For MspI SNP, our data indicated that carriers of TC and CC genotypes had a 34% increased risk to develop head and neck cancers compared to TT carriers (95% CI = 1.15-1.57, P < 0.001). This effect was even more pronounced in smokers (OR = 2.98, 95% CI = 1.69-5.26, P < 0.001), demonstrating that gene-smoking interaction intensifying carcinogenesis may exist. These findings reveal that the functional CYP1A1 MspI genetic variant, alone and in combination with smoking, plays a more important role in pathogenesis of head and neck cancers. (C) 2013 Elsevier Ltd. All rights reserved.