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

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 R 213 H with NAT2 × 5B L 161 L , SULT1A1 R 213 H with NAT2 × 5C K 268 R , EPHX1 H 139 R and NAT2 × 5B L 161 L exhibit a protective effect towards lung cancer risk. Further, the triple combinations of NQO1 P 187 S , EPHX1 Y 113 H , and EPHX1 H 139 R ; NQO1 P 187 S , EPHX1 Y 113 H , and NAT2 × 6 R 197 Q ; NQO1 P 187 S , EPHX1 Y 113 H , and NAT2 × 7 G 286 E ; SULT1A1 R 213 H , EPHX1 H 139 R , and NAT2 × 7 G 286 E 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.