High-order gene interactions between the genetic polymorphisms in Wnt and AhR pathway in modulating lung cancer susceptibility. (November 2017)

• Record Type: Journal Article
• Authors: Bahl, Charu; Singh, Navneet; Behera, Digambar; Sharma, Siddharth
• Is Part Of: Personalized medicine. Volume 14:Number 6(2017)
• Page Start: 487
• Page End: 502
• Publication Date: 2017-11
• Subjects: aryl hydrocarbon receptor -- interaction -- lung cancer -- polymorphisms -- risk -- Wnt; Pharmacogenomics -- Periodicals; Pharmacogenetics -- Periodicals; 615.19
• DOI: 10.2217/pme-2017-0018
• Languages: English
• ISSNs: 1741-0541

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, DKK2rs419558 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.