Synergistic polymorphic interactions of phase II metabolizing genes and their association toward lung cancer susceptibility in North Indians

ABSTRACT

Lung cancer is a multifactorial carcinoma with diverse heterogeneity. Genetic variations in drug-metabolizing enzymes may lead to defective detoxification and clearance of carcinogenic compounds. The high-order gene-gene interaction has been carried out between different genotypes of Phase II detoxification genes (NQO1, SULT1A1, NAT2, and EPHX1). Our results depict the genetic combination of SULT1A1 R²¹³H with NAT2 × 5B L¹⁶¹L, SULT1A1 R²¹³H with NAT2 × 5C K²⁶⁸R, EPHX1 H¹³⁹R and NAT2 × 5B L¹⁶¹L exhibit a protective effect towards lung cancer risk. Further, the triple combinations of NQO1 P¹⁸⁷S, EPHX1 Y¹¹³H, and EPHX1 H¹³⁹R; NQO1 P¹⁸⁷S, EPHX1 Y¹¹³H, and NAT2 × 6 R¹⁹⁷Q; NQO1 P¹⁸⁷S, EPHX1 Y¹¹³H, and NAT2 × 7 G²⁸⁶E; SULT1A1 R²¹³H, EPHX1 H¹³⁹R, and NAT2 × 7 G²⁸⁶E suggested a two-fold increased risk of lung cancer for subjects. Genetic polymorphisms of phase II detoxifying genes (NAT2, NQO1, EPHX1, SULT1A1) are prognostic markers for lung cancer.

KEYWORDS:

• Lung cancer
• polymorphism
• phase II enzymes
• high-order gene-gene interaction

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data generated from this research is provided in the manuscript. Any further queries can be directed to corresponding author

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/09603123.2022.2133095

Additional information

Funding

Any agency did not support this research.