Current evidence on the relationship between two common polymorphisms in NPAS2 gene and cancer risk

The relationship between neuronal PAS domain protein 2 (NPAS2) gene polymorphisms and cancer risk has been widely investigated. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation on the relationship. We searched Pubmed, and Web of Knowledge databases until Dec, 2014 to identify eligible studies. Case-control studies containing available genotype frequencies of the NPAS2 polymorphisms were chosen. The odds ratios (ORs) with 95% confidence interval (CI) were used to assess the strength of association. Eight independent case-control studies with 3,857 cancer patients and 4,525 cancer-free controls were selected for this meta-analysis. Two NPAS2 gene polymorphisms were identified (rs2305160 and rs17024926). The results showed statistically significant associations of rs2305160 with cancer risk (AA+GA vs. GG: OR = 0.84, 95% CI = 0.72-0.98, P = 0.02; AG vs. GG: OR = 0.81, 95% CI = 0.68-0.96, P = 0.02). Stratified analysis by cancer type indicated that rs2305160 may decrease the risk of breast cancer (A vs. G: OR = 0.87, 95% CI = 0.76-0.96, P = 0.006; AA+GA vs. GG: OR = 0.77, 95% CI = 0.67-0.88, P<0.001; AG vs. GG: OR = 0.74, 95% CI = 0.64-0.86, P<0.001), whereas negative results were obtained for prostate cancer. For rs17024926 polymorphism, there was no significant association in any genetic model. This meta-analysis suggests that NPAS2 rs2305160 polymorphism may reduce cancer susceptibility, especially in breast cancer.