High-order gene interactions between the genetic polymorphisms in Wnt and AhR pathway in modulating lung cancer susceptibility

Abstract

Aim: Genetic variations present within Wnt and AhR pathway might be related to the lung cancer susceptibility. Methods: A total of 555 subjects were genotyped using PCR-RFLP technique for polymorphic sites in DKK4, DKK3, DKK2, sFRP3, sFRP4, Axin2 and AhR. Multifactor dimensionality reduction method and classification and regression tree analysis was used. Results: Overall sFRP4rs1802073 which has a cross validation consistency of 10/10, prediction error = 0.43 (p > 0.0001) is the best factor model. The second best model was sFRP4rs1802073 and DKK2rs419558 with cross validation consistency of 9/10 and prediction error = 0.40. In classification and regression tree analysis, DKK2 rs419558 came out to be a significant factor; DKK2rs17037102 (M)/DKK2rs419558 (M) showed a tenfold risk of acquiring lung cancer, p = 0.0001. DKK2rs17037102 (M)/AhRrs2066853 (W)/AhRrs10250822 (M) showed an 11-fold risk of developing lung cancer, p = 0.00001. Conclusion: Both DKK2 and sFRP4 polymorphisms are found to play a crucial role; especially for smokers towards modulating risk for lung cancer. AhR variants are contributing maximally toward lung cancer risk.