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
Esophageal cancer, which is prevalent in China, is believed to be induced by environmental carcinogens such as nitrosamines and other agents. The disproportionate geographical distribution of this cancer among individuals suggests a role for gene-environment interactions in developing the disease. W...
Gespeichert in:
Veröffentlicht in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2000-06, Vol.9 (6), p.551-556 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Esophageal cancer, which is prevalent in China, is believed to be
induced by environmental carcinogens such as nitrosamines and other
agents. The disproportionate geographical distribution of this cancer
among individuals suggests a role for gene-environment interactions in
developing the disease. We have shown in our preliminary study that a
genetic polymorphism in cytochrome P450 2E1 ( CYP2E1 )
that is known to activate nitrosamines may be a susceptibility factor
involved in the early events leading to the development of esophageal
cancer (Lin et al. , Cancer Epidemiol. Biomark. Prev.,
7: 1013–1018, 1998). This relatively larger study was
conducted to compare the results 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 high-risk area. Genomic DNA samples were assayed for
restriction fragment length polymorphisms in the CYP2E1
and GSTP1 loci by PCR amplification followed by
digestion with Rsa I and Alw 26I,
respectively. Deletion of the GSTM1 and
GSTT1 genes was detected by multiplex PCR. The
distribution of CYP2E1 c1/c1 allele frequency was found
to be significantly 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 genotype were at a 3.1-fold[
95% confidence interval (CI), 2.4–3.9] increased risk 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
polymorphisms in the GSTT1 and GSTP1 were
not significantly different between cases with cancer or cases with
dysplasia and controls, the frequency of the GSTM1
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). Furthermore, a joint effect of the CYP2E1
c1/c1 genotype and GSTM1 non-null genotype 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 genetic determinants in the development of
squamous cell carcinoma of the esophagus. |
---|---|
ISSN: | 1055-9965 1538-7755 |