Short Communication Association of Aflatoxin B1-Albumin Adduct Levels with Hepatitis B Surface Antigen Status among Adolescents in Taiwan
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چکیده
Chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure interact synergetically to induce hepatocellular carcinoma. One suggested mechanism for this interaction is the enhanced activation of AFB1 in chronically HBV-infected individuals. Whereas no associations between chronic HBV infection and AFB1albumin adducts were observed in several studies in adults, hepatitis B surface antigen (HbsAg)-positive children were found to have elevated adducts in Gambia. To assess the association between chronic HBV infection and AFB1-albumin adduct level in Taiwan, 200 junior high school adolescents from 20 townships were assayed for HBsAg and AFB1-albumin adducts. The mean AFB1albumin adduct level was higher in HBsAg-positive compared with HBsAg-negative subjects. The association between HBsAg status and AFB1-albumin adducts remained after multivariate adjustment. This finding additionally supports the synergetic interaction between HBV and AFB1, but the mechanism remains to be elucidated. Introduction HCC is one of the most common cancers in the world and one of the leading malignancies in sub-Saharan Africa and Southeast Asia, including Taiwan (1, 2). Chronic HBV infection is the major cause of 80% of HCC (1–3). In Taiwan, HBV infection is hyperendemic with a 15–20% carrier rate of HBsAg in the general population (4). AFB1, a potent mycotoxin, has also been well documented as a risk factor in Taiwan (5–9). It is metabolized by the CYP (10) to a reactive epoxide that can bind to DNA, forming AFB1-guanine adducts, and to protein, forming AFB1-albumin adducts. Albumin adducts have been used extensively to investigate exposure to AFB1 in both etiological (6, 7, 11) and chemopreventive studies (12). A synergistic interaction between AFB1 exposure and HBV infection on HCC risk has been reported in several epidemiological studies (8, 13). Studies in several animal models including ducks and woodchucks infected with HBV as well as an HBV-transgenic mouse model also demonstrated a synergistic effect (14–16). One suggested mechanism for this effect is enhanced activation of AFB1 in HBV-infected animals with supporting data generated in one study (17) although conflicting data have also been reported (18). In humans, several previous studies in adults failed to find an association between HBsAg status and albumin adducts (11, 19, 20), whereas one study found higher levels of AFB1-guanine in urine of infected individuals (21). Three studies investigated this relationship in children, all in Gambia, and found higher AFB1-albumin adducts in infected compared with noninfected children 3–8 years of age (22, 23) and 3–4 years of age (24). To explore this association in another geographic area, we determined AFB1-albumin adducts and HBsAg status in 200 junior high school adolescents (13–15 years of age) from 20 townships in Taiwan. Materials and Methods Subjects and Sample Collection. Two hundred junior high school students (50 males positive and 50 males negative for HBsAg and a similar number of females) were selected through stratified random sampling from 875 adolescents recruited between January and May 1991 for a study of geographical variation in hepatitis A and B infection in 20 townships in Taiwan (25). The junior high school attendance rate in Taiwan was as high as 95%, and this birth cohort is the last not immunized against HBV at birth. Thus, we recruited a representative sample with no bias in their HBsAg carrier rate caused by the vaccination. Information on the previous 3-day dietary consumption pattern was obtained through a standardized questionnaire by interviewers. After collection, bloods were centrifuged and separated into aliquots; serum samples were stored at 70°C until tested. Overnight urine samples were also stored at 20°C until tested. The Measurement of HBsAg Status and AFB1-Albumin Adduct Level and Urinary Aflatoxins. HBsAg in serum was determined by enzyme immunoassay using commercial reagents (Abbott Laboratories, North Chicago, IL) according to the manufacturer’s manuals. AFB1-albumin adducts level was determined by competitive ELISA using a polyclonal antiserum (number 7) essentially as described previously (6, 8). Samples with 20% inhibition were considered nondetectable and asReceived 2/9/01; revised 8/23/01; accepted 9/11/01. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 This work was supported by National Institute of Environmental Health Sciences Grant ES05116 and P30ES09089 and Department of Health, Executive Yuan, Republic of China. 2 To whom requests for reprints should addressed, at Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, Room 505, 701 West 168 Street, New York, NY, 10032. Phone: (212) 3051996; Fax: (212) 305-5328; E-mail: rps1@columbia.edu. 3 The abbreviations used are: HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; AFB1, aflatoxin B1; CYP, cytochrome P450 system. 1223 Vol. 10, 1223–1226, November 2001 Cancer Epidemiology, Biomarkers & Prevention on September 7, 2017. © 2001 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from signed a value of 2 fmol/mg. The level of urinary aflatoxins was detected by ELISA as described previously (8). Statistical Analysis. AFB1-albumin adduct levels were natural logarithm-transformed to normalize the distribution. A t test was used to evaluate the differences in mean adduct levels (ln fmol/mg) by HBsAg status, sex, urinary aflatoxins, and consumption of peanut, corn, and yam/cassava in the past 3 days, as well as by HBsAg status after stratification by gender. Both univariate and multivariate linear regression analyses were conducted to examine associations of sex and HBsAg with AFB1albumin levels.
منابع مشابه
Variability in aflatoxin-albumin adduct levels and effects of hepatitis B and C virus infection and glutathione S-transferase M1 and T1 genotype.
Exposure to aflatoxin B1 (AFB1), an important cofactor in the etiology of hepatocellular carcinoma in Taiwan, is influenced by dietary and other factors. The present study examined the intraindividual variability in AFB1-albumin adducts, the most reliable long-term biomarker of AFB1 exposure, and whether the baseline or follow-up adduct levels and the intraindividual variability in adduct level...
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