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

Int J Environ Health Res. 2024 Jan;34(1):103-126. doi: 10.1080/09603123.2022.2133095. Epub 2022 Oct 17.


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; high-order gene-gene interaction; phase II enzymes; polymorphism.

MeSH terms

  • Arylamine N-Acetyltransferase* / genetics
  • Case-Control Studies
  • Genotype
  • Humans
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / genetics
  • Polymorphism, Genetic
  • Risk


  • Arylamine N-Acetyltransferase
  • NAT2 protein, human