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 sFRP4_rs1802073 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_rs1802073 and DKK2_rs419558 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; DKK2_rs17037102 (M)/DKK2_rs419558 (M) showed a tenfold risk of acquiring lung cancer, p = 0.0001. DKK2_rs17037102 (M)/AhR_rs2066853 (W)/AhR_rs10250822 (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.

Keywords::

• aryl hydrocarbon receptor
• interaction
• lung cancer
• polymorphisms
• risk
• Wnt

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pme-2017-0018

Financial & competing interests disclosure

This work was supported by grant from the Indian Council of Medical Research, New Delhi, India (Grant No. 5/13/126/2011/NCD-III). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Funding

This work was supported by grant from the Indian Council of Medical Research, New Delhi, India (Grant No. 5/13/126/2011/NCD-III). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.