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

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 sFRP4 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 sFRP4 and DKK2 with cross validation consistency of 9/10 and prediction error = 0.40. In classification and regression tree analysis, DKK2 came out to be a significant factor; DKK2 (M)/DKK2 (M) showed a tenfold risk of acquiring lung cancer, p = 0.0001. DKK2 (M)/AhR (W)/AhR (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.