GENETIC POLYMORPHISMS OF GLUTATHIONE S-TRANSFERASES M1 AND TI ASSOCIATED WITH SUSCEPTIBILITY TO AFLATOXIN- RELATED HEPATOCARCINOGENESIS AMONG CHRONIC HEPATITIS B CARRIERS: A NESTED CASE-CONTROL STUDY IN TAIWAN
Resource
CARCINOGENESIS v.22 n.8 pp.1289-1294
Journal
CARCINOGENESIS
Journal Volume
v.22
Journal Issue
n.8
Pages
1289-1294
Date Issued
2001
Date
2001
Author(s)
SUN, CHIEN-AN
WANG, LI-YU
CHEN, CHIEN-JEN
LU, SHENG-NAN
YOU, SAN-LIN
WU, DER-MI
Abstract
This study was conducted to investigate the modifying effect
of glutathione S-transferase (GST) M1 and T1 polymorphisms
on aflatoxin-induced hepatocarcinogenesis among chronic
hepatitis B virus surface antigen (HBsAg) carriers. A total
of 79 HBsAg-positive cases of hepatocellular carcinoma (HCC)
diagnosed between 1991 and 1997 were identified and
individually matched to one or two HBsAg-positive controls
on age, gender, residence and date of recruitment from the
same cancer screening cohort in Taiwan. Blood samples were
tested for hepatitis B and C viral markers by enzyme
immunoassay and for aflatoxin B-1 (AFB(1))-albumin adducts
by competitive enzyme-linked immunosorbent assay. GSTM1 and
GSTT1 genotypes were determined by PCR. There was a
statistically significant relationship between detectable
levels of AFB(1)-albumin adducts in serum and risk of HCC
among chronic HBsAg carriers, with an adjusted odds ratio (
OR) of 2.0 [95% confidence interval (CI) 1.1-3.7]. In
addition, the effect of aflatoxin exposure on HCC risk was
more pronounced among chronic HBsAg carriers with the GSTT1
null genotype (OR 3.7, 95% Cl 1.5-9.3) than those who were
nonnull (OR 0.9, 95% CI 0.3-2.4). The interaction between
serum AFB(1)-albumin adduct level and GSTT1 genotype was
statistically significant (P = 0.03). For GSTM1 the effect
of aflatoxin exposure on HCC risk in those with the null
genotype was also greater (adjusted OR 2.8, 95% CI 1.0-7.8)
than in those with the gene present (adjusted OR 1.8, 95% CI
0.8-4.5), but the difference was not significant (P = 0.91)
. Notably, when the interaction between aflatoxin exposure
and GSTT1 genotype was considered, aflatoxin exposure by
itself was not a significant determinant of HCC risk among
chronic HBsAg carriers. These results demonstrate the
importance of gene-environment interactions in the
multifactorial development of HCC.
Subjects
LUNG-CANCER RISK
HEPATOCELLULAR-CARCINOMA
LIVER-CANCER
T1 POLYMORPHISMS
THETA GSTT1
B-1
SDGs
Type
journal article