Potentially functional variants of Wnt signaling pathway genes predict risk of primary lung cancer in Chinese Han population

Wnt signaling is a highly conserved pathway that regulates cell proliferation, differentiation, apoptosis and stem cell self-renewal, which has implications for embryonic development and tumorigenesis. We investigated the potential role of candidate single nucleotide polymorphisms (SNPs) of Wnt signaling pathway genes with computational evidence of regulatory potential on lung cancer in Chinese Han patients. The case–control study included 1,143 diagnosed primary lung cancer patients and 1,172 healthy controls. It was identified that Wnt2 rs4730775, Axin1 rs1981492 and Dvl2 rs222851 were associated with increased risk of lung cancer (adjusted Odds Ratio [ORadj] = 1.227, 95% confidence interval [CI] = 1.020–1.477; ORadj = 1.460, 95% CI = 1.019–2.090; ORadj = 1.477, 95% CI = 1.200–1.819, respectively). Dvl2 rs222851 was associated with a noticeably increased risk of lung cancer using dominant model by multi-classification logistic regression analysis (ORadj = 1.437, 95% CI = 1.178–1.754). Meanwhile, it enhanced the predictive ability of lung cancer incidence with the area under the Receiver Operating Characteristic Curve (AUROC) increased to 0.742 (95% CI = 0.721–0.762). Additionally, the crossover analysis revealed that Dvl2 rs222851 risk genotypes along with cooking oil fume exposure increased lung cancer risk by 1.514-fold (ORadj = 2.514, 95% CI = 1.647–3.839). There was positive multiplicative interaction between rs222851 and cooking oil fume exposure (ORadj = 1.174, 95% CI = 1.055–1.306). Our findings indicated that the genetic mutation of Wnt2 rs4730775, Axin1 rs1981492 and Dvl2 rs222851 on Wnt signaling pathway could promote the occurrence of lung cancer in Chinese Han population. Additionally, the Dvl2 rs222851 variant was significantly associated with exposure to cooking oil fumes.