The Effect of <i>XPD</i> Polymorphisms on Digestive Tract Cancers Risk: A Meta-Analysis

<div><p>Background</p><p>The Xeroderma pigmento-sum group D gene (<i>XPD</i>) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that <i>XPD</i> polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between <i>XPD</i> Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer.</p><p>Methods</p><p>We searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.</p><p>Results</p><p>The results showed that <i>XPD</i> Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln <i>vs.</i> LysLys): OR = 1.12, 95% CI = 1.01–1.24, <i>P</i> = 0.029, <i>P</i><sub>heterogeneity</sub> = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01–1.63, <i>P</i> = 0.045, <i>P</i><sub>heterogeneity</sub> = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous.</p><p>Conclusions</p><p>Our meta-analysis suggested that the <i>XPD</i> 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.</p></div>