Association between the XPD/ERCC2 Lys751Gln polymorphism and risk of cancer: evidence from 224 case-control studies

Genetic variations in the xeroderma pigmentosum group D (XPD) gene may increase cancer susceptibility by affecting the capacity for DNA repair. A lot of studies have reported the association of XPD Lys751Gln polymorphism with risk of cancer, but the results remained controversial. Hence, we performed a systematic review and conducted a meta-analysis to explore association of the XPD Lys751Gln polymorphism with risk of cancer (78,398 cases and 103,178 controls from 224 studies). Overall, a significantly increased cancer risk was found in all genetic models (dominant model: odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.06-1.14; recessive model: OR = 1.10, 95% CI = 1.05-1.15; homozygous model: OR = 1.14, 95% CI = 1.08-1.21; heterozygous model: OR = 1.09, 95% CI = 1.05-1.12; additive model: OR = 1.08, 95% CI= 1.05-1.11) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk of cancer remained for subgroups of breast cancer, esophageal cancer, hepatocellular cancer, leukemia, lung cancer, and melanoma. In summary, this meta-analysis suggests the XPD Lys751Gln polymorphism is a genetic susceptibility for some cancer types. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the Lys751Gln on some cancer risk. In addition, our work also points out the importance of new studies for Lys751Gln association in endometrial cancer and ovarian cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the Lys751Gln polymorphism in cancer development.