Modulation of urinary excretion of green tea polyphenols (GTPs) and oxidative DNA damage biomarker, 8-hydroxydeoxyguanosine (8-OHdG), were assessed in urine samples collected from a randomized, double-blinded and placebo-controlled phase IIa chemoprevention trial with GTP in 124 individuals. These individuals were sero-positive for both HBsAg and aflatoxin-albumin adducts, and took GTP capsules daily at doses of 500 mg, 1000 mg or a placebo for 3 months. Twenty-four hour urine samples were collected before the intervention and at the first and third month of the study. Urinary excretion of 8-OHdG and GTP components was measured by HPLC-CoulArray electrochemical detection. The baseline levels of 8-OHdG and GTP components among the three groups showed homogeneity (P > 0.70), and a non-significant fluctuation was observed in the placebo group over the 3 months (P > 0.30). In GTP-treated groups, epigallocatechin (EGC) and epicatechin (EC) levels displayed significant and dose-dependent increases in both the 500 mg group and 1000 mg group (P < 0.05). The 8-OHdG levels did not differ between the three groups at the 1 month collection, with medians of 1.83, 2.08 and 1.86 ng/mg-creatinine for placebo, 500 and 1000 mg group, respectively (P = 0.999). At the end of the 3 months' intervention, 8-OHdG levels decreased significantly in both GTP-treated groups, with medians of 2.02, 1.03 and 1.15 ng/mg-creatinine for placebo, 500 mg and 1000 mg group, respectively (P = 0.007). These results suggest that urinary excretions of EGC and EC can serve as practical biomarkers for green tea consumption in human populations. The results also suggest that chemoprevention with GTP is effective in diminishing oxidative DNA damage.

BACKGROUND In Southern Guangxi, China, chronic infection with the hepatitis B virus (HBV) acquired during the perinatal period from carrier mothers is a primary cause of hepatocellular carcinoma. However, only a minority of HBV carriers eventually develop hepatocellular carcinoma. The authors hypothesized that cytokine genotypes may be important codeterminants of the risk of HBV‐related hepatocellular carcinoma. METHODS The authors examined the correlation between polymorphisms in T‐helper 1 (Th1) and Th2 cytokine genes among a group of 250 patients with incident hepatocellular carcinoma (cases) and a group of 250 hospital controls who were matched individually to the index case by age, gender, ethnicity, residence, and month of hospital admission in the city of Nanning, Guangxi, China. RESULTS Relative to the putative high‐activity genotypes, each individual low‐activity genotype of interferon γ, interleukin 12 (IL12), and IL18 was associated with a statistically nonsignificant increase (40–60%) in the risk of hepatocellular carcinoma. This risk increased with increasing numbers of low‐activity Th1 genotypes after adjusting for potential confounders (2‐sided P value for trend = 0.04). Conversely, individual Th2 (IL4, IL10) low‐activity genotypes were associated with a statistically nonsignificant reduced risk of hepatocellular carcinoma. This risk decreased with increasing number of low‐activity Th2 genotypes after adjusting for potential confounders (2‐sided P value for trend = 0.01). Individuals who had the maximum number (i.e., 3) of low‐activity Th1 genes and the minimum number (i.e., 0) of low‐activity Th2 genes showed a relative risk of 20.0 (95% confidence interval, 1.7–235.0). CONCLUSIONS Diminished cell‐mediated immune response, which is controlled genetically, appeared to be an important risk determinant of HBV‐related hepatocellular carcinogenesis. Cancer 2005. © 2005 American Cancer Society.

beta-Catenin plays a key role in the Wnt signaling pathway, and mutations of CTNNB1, the gene that encodes beta-catenin, have been identified in about one-fourth of human hepatocellular carcinomas from regions of low aflatoxin B1 exposure. In this study 62 hepatocellular carcinomas (HCCs) from people highly exposed to aflatoxin B1 in Guangxi, People's Republic of China, were laser-capture microdissected and examined for CTNNB1 mutations. In addition, 41 of the HCCs were evaluated for the presence of the beta-catenin protein by immunohistochemical methods. Twenty of the HCCs showed positive results for beta-catenin, with strong membrane staining, while adjacent non-neoplastic liver tissue lacked or showed only weak membrane staining. One HCC, in which a CTNNB1 mutation was not detected, showed nuclear staining for the beta-catenin protein. Mutations of CTNNB1 were identified in five HCCs. These consisted of four point mutations in the glycogen serine kinase-3beta phosphorylation region of codons 32-45 and one deletion of codons 32-38. These mutations were similar to those previously reported for human HCC, although at a lower frequency. A signature mutation profile associated with aflatoxin B1 exposure could not be identified. The immunohistochemical findings indicate a role for accumulation of beta-catenin and possibly increased Wnt signaling in aflatoxin B1-associated HCC. The low frequency of CTNNB1 mutations, however, suggests that mutation of another Wnt signaling component, such as the Wnt scaffolding protein axin or the adenomatous polyposis coli protein, both of which modulate beta-catenin stability, also may be involved in aflatoxin-associated HCC. Published 2001 Wiley-Liss, Inc.

H epatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer deaths. 1 The overall 5-year survival for patients with HCC is less than 10%.Only 30% of patients with HCC are considered candidates for surgical resection; however, the recurrence rate after surgery is approximately 40% to 50%. 2 The major risk factors for HCC vary somewhat with its geographical distribution. Chronic infection with hepatitis B virus (HBV) is by far the most important risk factor for HCC in humans and is the primary cause of this cancer in highrisk areas, including China and Africa. 3,4 Chronic infection with hepatitis C virus (HCV) is another risk factor for HCC and has an increasingly prominent role in the development of HCC in countries such as the United States where rates of infection with HBV are relatively low. 5 Other environmental risk factors for HCC include dietary aflatoxin, which plays a prominent role in highrisk areas such as China and Africa; excessive alcohol intake; cigarette smoking; diabetes; and obesity. [6][7][8] Given that only a minority of people exposed to these risk factors eventually develop HCC, other cofactors (environmental and/or genetic) are likely to be involved in the development of HCC in humans.Experimental studies have shown that diets deficient in methyl groups (folate, methionine, and choline) can induce HCC in rodents 9,10 along with an increased level of uracil in DNA and accumulated DNA strand breaks in the P53 gene of the hepatocytes. [11][12][13] Thymidylate is a

This paper was translated from Chinese into English by Guangzhou Liheng Medical Translation and edited by Wei Liu on 20100330.