In stratified analyses, the NQO1Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians.
In the second part, we found that the FDA-approved non-steroidal anti-inflammatory drug sulindac and its metabolites, sulindac sulfide and sulindac sulfone, increased NQO1 expression and activity in the lung adenocarcinoma cell lines CL1-1 and CL1-5, which have lower NQO1 levels and lower sensitivity to β-lapachone treatment than the A549 cell lines, and that inhibition of NQO1 by either dicoumarol treatment or NQO1 siRNA knockdown inhibited this sulindac-induced increase in β-lapachone cytotoxicity.
Four MMPs (MMP1, MMP7, MMP9 and MMP12), which were upregulated in lung AC, were clustered into one group with other genes, including NAD(P)H quinone oxidoreductase 1, claudin 3 (CLDN3), S100 calcium-binding protein P, serine protease inhibitor Kazal type 1, collagen type XI α 1 chain, periostin and desmoplakin (DSP), following cluster analysis.