Several polymorphisms (Lys(939)Gln, PAT+/- and Ala(499)Val) in the DNA nuclear excision repair gene xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on cancer risk. In this meta-analysis, we assessed reported studies of associations between three XPC polymorphisms and risk of cancers from 16 studies with 6797 cases and 9018 controls for Lys(939)Gln, from 11 studies with 5581 cases and 6351 controls for Ala(499)Val and from 16 studies with 4514 cases and 5538 controls for PAT+/-. We found an increased overall cancer risk for variant homozygotes of Lys(939)Gln (OR=1.16, 95% CI, 1.05-1.28) and Ala(499)Val (OR=1.24, 95% CI, 1.08-1.42) compared with their corresponding wild-type homozygotes. When stratified by cancer type, the variant (939)Gln homozygous genotype was a risk factor for lung cancer (OR=1.28, 95% CI, 1.07-1.53), whereas the (499)Val variant homozygous genotype was a risk factor for bladder cancer (OR=1.33, 95% CI, 1.06-1.68) compared with their corresponding wild-type homozygous genotypes. For the XPC-PAT polymorphism, we found a decreased cancer risk associated with the PAT+/- genotype only in Asians compared with the PAT-/- genotype. Five studies were pooled for stratification analysis to explore the gene-smoking interaction. There was a joint effect of PAT +/+ and smoking in cancer risk. These analyses suggest that XPC Lys(939)Gln, PAT+/- and Ala(499)Val likely contribute to susceptibility to cancers. However, single larger studies with subjects of the same ethnic background and tissue-specific biochemical and biological characterisation are warranted to validate these findings.