Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan

Chien An Sun; Li Yu Wang; Chien Jen Chen; Sheng Nan Lu; San Lin You; Lian Wen Wang; Qiao Wang; Der Ming Wu; Regina M. Santella

doi:10.1093/carcin/22.8.1289

Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan

Chien An Sun^*, Li Yu Wang, Chien Jen Chen, Sheng Nan Lu, San Lin You, Lian Wen Wang, Qiao Wang, Der Ming Wu, Regina M. Santella

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

96 Scopus citations

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 B₁ (AFB₁)-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 AFB₁-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% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB₁-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.

Original language	English
Pages (from-to)	1289-1294
Number of pages	6
Journal	Carcinogenesis
Volume	22
Issue number	8
DOIs	https://doi.org/10.1093/carcin/22.8.1289
State	Published - 2001
Externally published	Yes

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Sun, C. A., Wang, L. Y., Chen, C. J., Lu, S. N., You, S. L., Wang, L. W., Wang, Q., Wu, D. M., & Santella, R. M. (2001). Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan. Carcinogenesis, 22(8), 1289-1294. https://doi.org/10.1093/carcin/22.8.1289

@article{6b81e1f69cf641a9bc6373d85bc3ccf1,

title = "Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan",

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 B1 (AFB1)-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 AFB1-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% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB1-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.",

author = "Sun, {Chien An} and Wang, {Li Yu} and Chen, {Chien Jen} and Lu, {Sheng Nan} and You, {San Lin} and Wang, {Lian Wen} and Qiao Wang and Wu, {Der Ming} and Santella, {Regina M.}",

year = "2001",

doi = "10.1093/carcin/22.8.1289",

language = "英语",

volume = "22",

pages = "1289--1294",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "8",

}

Sun, CA, Wang, LY, Chen, CJ, Lu, SN, You, SL, Wang, LW, Wang, Q, Wu, DM & Santella, RM 2001, 'Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan', Carcinogenesis, vol. 22, no. 8, pp. 1289-1294. https://doi.org/10.1093/carcin/22.8.1289

Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan. / Sun, Chien An; Wang, Li Yu; Chen, Chien Jen et al.
In: Carcinogenesis, Vol. 22, No. 8, 2001, p. 1289-1294.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers

T2 - A nested case-control study in Taiwan

AU - Sun, Chien An

AU - Wang, Li Yu

AU - Chen, Chien Jen

AU - Lu, Sheng Nan

AU - You, San Lin

AU - Wang, Lian Wen

AU - Wang, Qiao

AU - Wu, Der Ming

AU - Santella, Regina M.

PY - 2001

Y1 - 2001

N2 - 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 B1 (AFB1)-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 AFB1-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% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB1-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.

AB - 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 B1 (AFB1)-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 AFB1-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% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB1-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.

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U2 - 10.1093/carcin/22.8.1289

DO - 10.1093/carcin/22.8.1289

M3 - 文章

C2 - 11470760

AN - SCOPUS:0034897931

SN - 0143-3334

VL - 22

SP - 1289

EP - 1294

JO - Carcinogenesis

JF - Carcinogenesis

IS - 8

ER -

Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: A nested case-control study in Taiwan

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