Association ofGSTT1polymorphism with acute myeloid leukemia risk is dependent on smoking status

Abstract

Genetic polymorphisms in drug-metabolizing, DNA repair and multidrug resistance genes affect the risks for many cancers. We analyzed 21 polymorphisms in 17 genes in these pathways to evaluate their association with the risk of acute myeloid leukemia (AML) and to examine whether smoking modifies these associations in a population-based study in Korea (415 cases, 1700 controls). We found marginal associations between the risk of AML and CYP1A1 1188, and XRCC1 194, ERCC1 IVS5 + 33 and WRN 787 polymorphisms. However, when we performed the analysis according to smoking exposure, we found a stronger association for ERCC1 only in the non-smoking population (odds ratio [OR] = 0.74; 95% confidence interval [CI] = 0.60-0.91, p = 0.004), while we found the GSTT1-null genotype to be associated with an increased risk of AML in ever-smokers (OR = 1.51; 95% CI = 1.06-2.15, p = 0.02). These results indicate that ERCC1 and GSTT1-null polymorphisms may have an effect on AML risk that is dependent on smoking exposure.

Risk Effects of GST Gene Polymorphisms in Patients with Acute Myeloid Leukemia: A Prospective Study

“…Similarly, Liu reported variation of GSTT1 genotype is not associated with the susceptibility of AML in a Chinese population (Liu et al, 2005). While a casecontrol study conducted in Brazil with 124 cases reported a moderate association between GSTT1 null genotype and risk of AML (Arruda et al, 2001), and Kim et al also reported a positive association in Korean population (Kim et al, 2012). In our study, we did not find the association of GSTM1 null and the GSTP1 Val/Val genotypes with AML, while we found GSTT1 null genotype was associated with increased risk of AML.…”

“…Previous several studies reported the association between GSTT1 polymorphisms and risk of AML (Crump et al, 2000;Arruda et al, 2001;Liu et al, 2005;Kim et al, 2012), but the results are inconsistent. Crump et al reported a case-control study conducted in the United States, and the results do not the hypothesis that the GSTT1 gene deletion is related to the risk of AML (Crump et al, 2000).…”

Smoking and subsequent risk of leukemia in Japan: The Japan Public Health Center-based Prospective Study

“…Another case–control study of 722 cases and 1444 controls in China also reported that cigarette smoking increased the risk of AML, with an OR relative to never smokers of 1.28 (95% CI, 1.00–1.63) for ever smokers 9 . In contrast, a case–control study of 415 cases and 1700 controls in Korea reported no significant association between the risk of AML and ever-smoking (OR relative to never smokers, 0.98; 95% CI, 0.79–1.22) 10 . The only prospective cohort study, which involved 1,212,906 participants and 355 leukemia cases in Korea, reported no significant increased risk of leukemia overall among men, with HRs for current smokers relative to never smokers of 1.1 (95% CI, 0.8–1.5) 7 .…”

Glutathione S-transferase Gene Polymorphisms and Susceptibility to Acute Myeloid Leukemia: Meta-analyses

“…3C) and the recessive model (Fig. 3D) (2,20,27,34,37) (the study of Yuan et al was excluded in homozygotes contrast and recessive model as the number of GG genotype in the AML group was 0). No association between the SNP and the susceptibility to AML was found under any contrast model, and no heterogeneity was found under any model.…”