Glutathione S-transferase T1-null genotype interacts synergistically with heavy smoking on lung cancer risk

We studied the influence of genotype for glutathione S-transferase TI (GSTT 1) on susceptibility to lung cancer among 184 Swedish lung cancer patients (88 never-smokers and 96 ever-smokers) and 162 matched population controls (79 never-smokers and 83 ever-smokers), with special emphasis on gene-envir onment interactions. Cases had significantly lower frequency of the GSTT1-n ull genotype than that of controls among never-smokers (4.6 vs. 16.5%, P = 0.02), whereas the frequencies were very close to each other among smokers (7.4 vs. 7.2%). Cases with high packyears of smoking, however, had a signif icantly higher frequency of the GSTT1-null genotype compared to that of cas es with low packyears (18.3 vs. 5.6%, P = 0.005). Adjusted for age and gend er, the GSTT1-null genotype appeared to be protective against lung cancer a mong never-smokers (odds ratio [OR] = 0.2, 95% confidence interval [Cl] = 0 .07-0.7), although it was associated with an increased risk for lung cancer among smokers (OR = 2.1, 95% Cl = 0.8-5.9), mainly attributed to the group of heavy smokers (> 23 packyears; OR = 3.5, 95% Cl = 0.7-17.3). Heavy smok ing conferred a threefold increased risk for lung cancer (OR = 2.6, 95% Cl = 1.3-5.0) among GSTT1-positive individuals, but a ninefold increased risk when combined with the GSTT1-null genotype (OR = 9.3, 95% Cl = 1.9-46.3, re lative to GSTT1-positive light smokers). This joint effect was Further demo nstrated by a positive interaction between the GSTT1-null genotype and pack years of smoking. The risk of lung cancer increased steeply with increasing packyears among GSTT1-null smokers, whereas no such effect was seen among GSTT1-positive smokers. We conclude that the GSTT1-null genotype may streng then the effect of heavy smoking on lung cancer risk. (C) 2001 Wiley-Liss, Inc.