Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China
W. Tan et al., Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China, CANC EPID B, 9(6), 2000, pp. 551-556
Esophageal cancer, which is prevalent in China, is believed to be induced b
y environmental carcinogens such as nitrosamines and other agents. The disp
roportionate geographical distribution of this cancer among individuals sug
gests a role for gene-environment interactions in developing the disease. W
e have shown in our preliminary study that a genetic polymorphism in cytoch
rome P450 2E1 (CYP2E1) that is known to activate nitrosamines mag be a susc
eptibility factor involved in the early events leading to the development o
f esophageal canter (Lin Et al,, Cancer Epidemiol, Biomark, Prev,, 7: 1013-
1018, 1998), This relatively larger study was conducted to compare the resu
lts with our previous findings. One hundred and fifty cases with esophageal
cancer, 146 cases with esophageal dysplasia, and 150 normal controls were
residents of Linxian, China, a highrisk area. Genomic DNA samples were assa
yed for restriction fragment length polymorphisms in the CYP2E1 and GSTP1 l
oci by PCR amplification followed by digestion with RsaI and Alw26I, respec
tively. Deletion of the GSTM1 and GSTT1 genes was detected by multiples PCR
, The distribution of CYP2E1 c1/c1 allele frequency was found to be signifi
cantly different between controls (44.0%) and cases with cancer (71.3%) or
cases with dysplasia (70.6%; P < 0.0001), Individuals having the c1/c1 geno
type were at a 3.1-fold [95% confidence interval (CI), 2.4-3.9] increased r
isk of developing dysplasia and a 3.2-fold (95% CI, 2.5-4.1) increased risk
of developing squamous cell carcinoma of the esophagus, Although polymorph
isms in the GSTT1 and GSTP1 were not significantly different between cases
with cancer or cases with dysplasia and controls, the frequency of the GSTM
1 non-null (+/+ and +/0) genotypes appeared to be overrepresented in cases
with cancer compared with controls (odds ratio, 2.3; 95% CI, 1.8-3.0). Furt
hermore, a joint effect of the CYP2E1 c1/c1 genotype and GSTM1 non-null gen
otype on the cancer risk was observed, showing an odds ratio of 8.5 (95% CI
, 3.7-19.9). These results demonstrate that CYP2E1 and perhaps GSTM1 are ge
netic determinants in the development of squamous cell carcinoma of the eso
phagus.