Genetic variation of XPA gene and risk of cancer: a systematic review and pooled analysis.

XPA, a zinc-finger DNA-binding protein, play an important role in both global genome and transcription-coupled repair pathways. XPA -4G>A polymorphism was identified in the 5' noncoding region, located four nucleotides upstream of the ATG start codon. Previous studies have shown that this polymorphism may affect mRNA tertiary structure and stability and play a role in susceptibility to cancer. However, the results remained controversial. To derive a more precise estimation of association between this polymorphism and risk of different types of cancer, we performed a meta-analysis based on 36 case-control or case-cohort studies, including a total of 11,700 cases and 15,033 controls. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, no significantly elevated cancer risk was found in all genetic models when eligible studies were pooled into the meta-analysis. In the stratified analyses, we found that individuals with A-allele had a higher risk of lung cancer (AA versus GG: OR = 1.25, 95% CI = 1.09-1.43; recessive model: OR = 1.31, 95% CI = 1.16-1.48). When stratified by ethnicity, significantly elevated risks were observed among Asian populations (AA versus GG: OR = 1.31, 95% CI = 1.01-1.70; dominant model: OR = 1.14, 95% CI = 1.00-1.30). This meta-analysis suggests that XPA -4G>A polymorphism is associated with increased lung cancer risk and may be a low-penetrant risk factor in Asian ethnicity for cancer development.