Short Communication Hepatocellular Carcinoma and Aflatoxin Exposure in Zhuqing Village, Fusui County, People’s Republic of China

Hepatocellular carcinoma (HCC) is a common cause of cancer morbidity and mortality in Asia and Africa. Epidemiological studies have found that dietary exposure to aflatoxin B1 (AFB1) and chronic infection with hepatitis B virus are two major risk factors for HCC. We have collated the incidence and mortality data of malignant tumors from 1973 to 1999 in Zhuqing Village, Fusui County, an area with very high HCC rates, and found that this cancer accounted for 64% of the total cancer incidence. Dietary intake of AFB1 was monitored for 1 week in a study group consisting of 15 males and 14 females from different households in this village. Four of 29 participants (13.8%) and 3 of 15 (20%) male participants were hepatitis B virus surface antigen positive. AFB1 was detectable in 76.7% (23 of 30) of ground corn samples (range, 0.4–128.1 ppb), 66.7% (20 of 30) of cooking peanut oil samples (range, 0.1–52.5 ppb), and 23.3% (7 of 30) of rice samples (range, 0.3–2.0 ppb) collected from each household. Mean levels of serum AFB1-albumin adducts in this group were 1.24 6 0.31 pmol/mg of albumin at the beginning of the study and 1.21 6 0.19 pmol/mg of albumin at the end of the period. Urinary AFB1 metabolites were detectable in 88.9% (24 of 27) samples (range, 0.9–3569.7 ng/24-h urine). These data provide the exposure and disease risk information for establishing intervention studies to diminish the impact of aflatoxin exposure in this high-risk population. Introduction HCC is one of the most common cancers in Asia, Africa, and in groups of Asianand Hispanic-Americans, and is a leading cause of cancer death (1–3). In the People’s Republic of China, HCC is the second leading cause of cancer mortality, and in one high-risk region, Fusui County in Guangxi Zhuang Autonomous Region, the annual incidence rate is .50 cases per 100,000 people (4, 5). HCC usually strikes people at earlier ages in high-risk areas where the median age of onset of this malignancy is between 35 and 50 years. Previous epidemiological studies have found that chronic infection with HBV and dietary aflatoxin exposure are two major etiological risk factors for HCC in China (6–10). The synergistic interaction of HBV infection, aflatoxin exposure, and HCC has been observed in populations in Fusui County (11), Shanghai (12, 13), and other regions (14, 15). To date, there is still a low prevalence of hepatitis C virus infection in these areas of the People’s Republic of China (16, 17). Primary prevention, such as vaccination for HBV in infants and food safety procedures to control aflatoxin contamination, offer strategies for lowering HCC rates in the world; however, positive outcomes will require many years. An immediate challenge in cancer prevention and control is to manage those who are already at high risk, such as individuals who are HBsAg carriers and have chronic aflatoxin exposure. The purpose of the following study was to characterize HCC incidence and mortality, status of dietary aflatoxin exposure, and HBV infection in the high-risk region of Fusui County for use in the design of future chemopreventive intervention studies (18, 19). Materials and Methods Study Population. Zhuqing Village, located 45 km southwest of Fusui County capital, is a rural farming community of ;3300 residents and is one of the three townships with the highest incidence and mortality of HCC in Fusui County. Data for analyses of incidence and mortality of malignant tumors were collected from village clinics and were confirmed by the Office of Malignant Tumor Reporting operated by the Fusui Liver Cancer Institute. The incidence and mortality were standardized according to the National Population Proportion of China in 1990. Procedure for Molecular Biomarkers Study. This collaborative study by the Johns Hopkins University, Guangxi Cancer Institute, Shanghai Cancer Institute, and Fusui Liver Cancer Institute used methods and consent forms approved by the Institutional Review Boards for human studies at Johns HopReceived 7/19/00; revised 10/24/00; accepted 11/17/00. 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 financially by Program Project Grant ES06052 from the National Institute for Environmental Health Sciences, NIH. 2 To whom requests for reprints should be addressed, at The Institute of Environmental and Human Health, Texas Tech University System, Box 41163, Lubbock, TX 79409-1163. Phone: (806) 885-0320; Fax: (806) 885-4577; E-mail: [email protected]. 3 The abbreviations used are: HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBs, hepatitis B surface protein; HBc, hepatitis B core protein; HBe, hepatitis B virus envelope; AFB1, aflatoxin B1; AFM1, aflatoxin M1. 143 Vol. 10, 143–146, February 2001 Cancer Epidemiology, Biomarkers & Prevention on June 21, 2017. © 2001 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from kins University and at the Guangxi Cancer Institute. The consent form in bilingual (Chinese and English) format was developed, approved, and explained in detail at village meetings among residents and investigators prior to recruitment. To be eligible, participants had to meet the following criteria: adults 25–60 years of age in good general health with no history of chronic illness, no personal history of cancer, no use of prescribed medications, no pregnancy or lactation for women residents of different households, agree to stay in the village for the 1-week study period, and able to provide necessary informed consent. In April 1999, weighed portions of each meal from the participants and 24-h urine in three cycles (morning, noon, and evening) were collected from participants for 7 consecutive days. The urine volume was measured and tested with chemsticks for renal function, and a 200-ml urine aliquot per day was stored at 220°C. In addition, 10 ml of blood were drawn into Vacutainers at the beginning and 5 ml at the end of the 7-day study from each participant. Serum samples were immediately separated by centrifugation at the village clinic and stored at 220°C until analysis. Measurement of HBV Seromarkers and Liver Function. All serum samples were tested for HBsAg and anti-HBs by RIA using the AUSRIA II kit (Abbott Laboratories, North Chicago, IL). A test for the presence of anti-HBc and HBe antigen/antiHBe was then performed using a commercially available Corab kit purchased from Abbott Laboratories. Liver function tests (aspartate aminotransferase, alanine aminotransferase, and a-fetoprotein) were performed in the clinical laboratory of Guangxi Tumor Hospital, which is affiliated with Guangxi Cancer Institute and Guangxi Medical University, according to the clinical diagnostic procedures. Measurement of AFB1 in Food, Serum Albumin Biomarkers, and Urinary Biomarker. Food analysis for AFB1 was performed using a previously published immunoaffinity method (20). Urinary aflatoxin biomarkers and serum aflatoxinalbumin adducts were analyzed according to previously published methods (19, 21). Statistical Analysis. All analytical data are expressed as mean 6 SE, and levels of serum aflatoxin-albumin adducts were compared between the beginning and end of the study and statistically analyzed by Student’s t test. Raw data of cases and deaths were adjusted to standardized incidence and mortality using the National Population Proportion of China in 1990. Time trends analyses were performed according to the method described by Parkin et al. (2).