目的 了解江苏省启东地区肝癌患者ABO血型分布情况,探讨ABO血型与肝癌发病风险的关系.方法 选择1701例启东籍肝癌患者、2828例排除疾病后的启东籍健康体检人员,采集两组外周静脉血检测ABO血型,分析ABO血型与肝癌发生风险的关系.结果 1701例肝癌患者中,血型为A型者518例(30.45％)、B型者436例(25.63％)、O型者518例(30.45％)、AB型者 229例(13.46％);2828例体检健康者中,血型为A型者862例(30.48％)、B型者818例(28.93％)、O型者853例(30.16％)、AB型者295例(10.43％),与健康人群比较,肝癌患者中AB型比例高、B型比例低(P均<0.05).B型的启东籍人群发生肝癌的风险低(OR=0.847,95％CI:0.739～0.970),AB型启东籍人群发生肝癌的风险高(OR=1.336,95％CI 1.111～1.606).与健康人群比较,男性肝癌患者B型比例低、AB型比例高(χ2=5.618,11.01;OR分别为0.809,1.534;P均<0.05).结论 江苏省启东地区肝癌的发生与ABO血型有关,AB型人群发生肝癌的风险高,B型人群发生肝癌的风险低.

Supplementary Tables from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China

Background: Airborne pollutants have collectively been classified as a known human carcinogen and, more broadly, affect the health of hundreds of millions of people worldwide. Benzene is a frequent component of air pollution, and strategies to protect individuals against unavoidable exposure to this and other airborne carcinogens could improve the public's health. Earlier clinical trials in Qidong, China, demonstrated efficacy in enhancing the detoxication of benzene using a broccoli sprout beverage. Objectives: A randomized, placebo-controlled, multidose trial of a broccoli sprout beverage was designed to determine the lowest effective concentration that enhances benzene detoxication adjudged by enhanced excretion of the urinary biomarker, S-phenylmercapturic acid (SPMA). Methods: Following informed consent, 170 subjects were randomly assigned in 5 blocks of 34 each to drink either a placebo beverage (n = 55) or 1 of 3 graded concentrations of a broccoli sprout beverage [full (n = 25), one-half (n = 35), and one-fifth (n = 55)] for 10 consecutive days. Concentrations of SPMA arising through induced benzene conjugation with glutathione were quantified by MS in sequential 12-h overnight urine collections during the intervention. Results: MS was also used to quantify urinary sulforaphane metabolites in each dosing regimen that resulted in a median 24-h urinary output of 24.6, 10.3, and 4.3 mu mol, respectively, confirming a dose-dependent de-escalation of the inducing principle within the beverage. A statistically significant increase in benzene mercapturic acids in urine was found for the high-dose group (+63.2%) during the 10-d period. The one-half dose (+11.3%) and one-fifth dose groups (-6.4%) were not significantly different from placebo controls. Conclusions: An intervention with a broccoli sprout beverage enhanced the detoxication of benzene, an important airborne pollutant, when dosed at a concentration evoking a urinary elimination of similar to 25 mu mol sulforaphane metabolites per day, and it portends a practical and frugal population-based strategy to attenuate associated long-term health risks of air pollution.

Qidong hepatitis B virus (HBV) infection cohort (QBC) is a prospective community-based study designed to investigate causative factors of primary liver cancer (PLC) in Qidong, China, where both PLC and HBV infection are highly endemic. Residents aged 20-65 years, living in seven townships of Qidong, were surveyed using hepatitis B surface antigen (HBsAg) serum test and invited to participate in QBC from June 1991 to December 1991. A total of 852 and 786 participants were enrolled in HBsAg-positive and HBsAg-negative sub-cohorts in May 1992, respectively. All participants were actively followed up in person, received HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP) tests and upper abdominal ultrasonic examination, and donated blood and urine samples once or twice a year. The total response rate was 99.6%, and the number of incident PLC was 201 till the end of February 2017. The ratio of incidence rates was 12.32 (95% confidence interval[CI]=7.16-21.21, P < 0.0001) in HBsAg-positive arm compared with HBsAg-negative arm. The relative risk of PLC was 13.25 (95% CI=6.67-26.33, P < 0.0001) and 28.05 (95% CI=13.87-56.73, P < 0.0001) in the HBsAg+/HBeAg- group and the HBsAg+/HBeAg+ group, respectively, as compared to the HBsAg-/HBeAg- group. A series of novel PLC-related mutations including A2159G, A2189C and G2203W at the C gene, A799G, A987G and T1055A at the P gene of HBV genome were identified by using samples from the cohort. The mutation in hepatitis B virus (HBV) basal core promoter region of HBV genome has an accumulative effect on the occurrence of PLC. In addition, the tripartite relationship of aflatoxin exposure, P53 mutation and PLC was also investigated. Dynamic prediction model for PLC risk by using its long-term follow-up information and serial blood samples for QBC was developed. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.

Objective To explore the relationship of hepatitis B virus surface antigen(HBsAg)infec-tion and family history of hepatocellular carcinoma(HCC)with age at primary liver cancer. Methods Totally 1 359 cases of primary liver cancer were enrolled. Their data of sex,HBsAg status and family history informa-tions of liver cancer were analyzed on the associations with diagnosis age. Results Of the 1 359 cases,1 053 were males and 306 were females,their average age at diagnosis was(54. 02 ± 10. 47)years(20-84 years). For HBsAg positive cases,the average age at diagnosis was 51. 99,significantly younger than that of HBsAg negative cases(61. 23),t = 13. 51,P = 0. 000. Cases with family history of HCC were diagnosed at a signifi-cantly earlier age than those without family history(52. 53 vs 55. 23,t = 4. 389,P = 0. 000). In HBsAg posi-tive cases,the average age at diagnosis showed a significant difference not only between males and females (51. 18 vs 54. 89,t = 5. 353,P = 0. 000),but also between cases with family history and cases without family history(51. 33 vs 52. 62,t = 2. 233,P = 0. 026). In HBsAg negative cases,the average age at diagnosis of males and females were 60. 83 and 62. 45 respectively(t = 1. 126,P = 0. 261). The average age at diagnosis of cases with family history and cases without family history were 59. 58 and 61. 92 respectively(t = 1. 728,P =0. 085),both showed no significant difference. Conclusion Cases of primary liver cancer with positive-HBsAg are diagnosed averagely 9. 24 years younger than those with negative-HBsAg in Qidong. Sex and family history of HCC significantly advance hepatocarcinogenesis only in HBsAg positive individuals,not in HBsAg negative individuals.

OBJECTIVE To evaluate whether first-degree family history of liver cancer plays a role in liver cancer incidence by prospective evaluation of a patient cohort in Qidong, China over a 20-year period. METHODS In May 1992, 708 hepatitis B surface antigen (HBsAg) carriers and 730 HBsAg-negadve controls from Qidong city were enrolled for participation in a prospective cohort study ending in November 2012.Follow-up was carried out every 6 to 12 months, and evaluations included serum assays to measure concentrations of alpha fetoprotein (AFP), HBsAg and alanine aminotransferase (ALT), as well as abdominal ultrasound to assess liver disease.The relationship between baseline (study entry) information of patients with first-degree family history of liver cancer and liver cancer incidence during the two decades of study was statistically assessed. RESULTS There were 172 newly diagnosed liver cancer cases in the cohort during 25 753 person-years (py) of follow-up, representing an incidence of 667.88/100 000 py.The incidence rates of liver cancer among participants with or without liver cancer family history were 1 244.36/100 000 py and 509.70/100 000 py respectively, and the between-group difference reached the threshold for statistical significance (P less than 0.01, Relative Risk (RR):2.44, 95% Confidence Interval (CI):1.80-3.31).The incidence rates of liver cancer among participants who had a sibling with liver cancer and participants who had a parent with liver cancer were not significantly different (P > 0.05), but the liver cancer incidence among participants who had a mother with liver cancer was significantly higher than that of participants who had a father with liver cancer (P < 0.05, RR:1.86, 95% CI:1.03-3.36). Among the participants with liver cancer family history, 56.52% (39/69) were diagnosed before 50 years old, and this rate was significantly higher than that of participants without a family history of liver cancer (40.78%, 42/103, P less than 0.05).The incidence rate of liver cancer among the participants who were family history-positive and HBsAg-positive was significantly higher than that of participants who were family history-negative but HBsAg-positive (P < 0.01, RR:1.75, 95% CI:1.29-2.38), and was 59.59 times higher than for participants who were family history-negative and HBsAgnegative.Subgroup analysis of liver cancer incidence among participants who were family history-positive but HBsAg-negative and participants who were family history-negative and HBsAg-negative produced anRR of 2.60, but there was no statistically significant difference between the two subgroups (P > 0.05).At the study's end, the incidence rates of liver cancer for the different subgroups were 32.21% for the family history-positive and HBsAgpositive participants, 19.80% for the family history-negative and HBsAg-positive participants, 1.71% for the family history-positive and HBsAg-negative participants, and 0.65% for the family history-negative and HBsAg-negative participants. CONCLUSION First-degree family history of liver cancer is a risk factor of liver cancer in Chinese patients from Qidong, and exhibits synergism with HBsAg-positivity for incidence of liver cancer.

Background/Aim: Hepatitis B Virus (HBV) mutations play a role in the development of hepatocellular carcinoma (HCC). However, the association between HBV polymerase gene mutations and HCC has not been reported. In this study, we conducted a multi-stage study to identify HCC-related mutations in the reverse transcriptase (RT) domain of the HBV polymerase gene.Methods: A total of 231 HCCs and 237 non-HCC controls from Qidong, China, were included in this study. The entire sequence of HBV RT was first compared between 29 HCC and 35 non-HCC cases, and candidate mutations were then evaluated in two independent validation sets.Results: There were 15 candidate mutations identified from the discovery set, with A799G and T1055A being consistently associated with HCC across all studies. A pooled analysis of samples revealed that A799G, A987G, and T1055A were independent risk factors for HCC, with adjusted odds ratios of 5.53 [95% confidence interval (CI), 1.69-18.10], 4.20 (95% CI, 1.15-15.35), and 3.78 (95% CI, 1.45-9.86), respectively. A longitudinal study showed that these mutations were detectable 45 years prior to HCC diagnosis.Conclusions: Our study provides evidence the first that HBV RT contains naturally occurring mutations that can be used as predictive markers for HCC.

Objective: To explore the relationship between the mutations in the reverse transcriptase(RT) domain of hepatitis B virus polymerase(HBV-P) gene and the occurrence and development of hepatocellular carcinoma(HCC). Methods: In this case-control study, the serum samples from 202 HCC patients and 202 chronic hepatitis B virus(CHB) carriers matching for age and gender were collected. The sequence of the RT domain of HBV-P gene was determined by direct sequencing following PCR amplifi cation. The relationship between the mutations in the RT domain of HBV-P gene and the occurrence and development of HCC was analyzed. Results: The T895A, A904T and C955T mutations in the RT domain of HBV-P gene were all signif icantly associated with HCC compared to non-HCC controls(P = 0.034, 47.5% vs 37.1%; P = 0.011, 5.4% vs 1.0%; P = 0.030, 5.4% vs 1.5%). Furthermore, the Logistic multivariate analysis showed that T895A was an independent risk factor for HCC [odds ratio(OR) = 2.230, 95% confi dence interval(CI): 1.230-4.044, P = 0.008]. A904T or C955T increased the risk of HCC occurrence either(OR = 6.523, 95% CI: 0.838-50.733; OR = 2.904,95% CI: 0.599-14.093), but it did not reach statistical signifi cance. The mutation rate of combined mutation occurrence either in A904 or C955T was 9.4% in HCC group and 2.5% in non-HCC controls(P = 0.003). The adjusted OR was 4.145(95% CI: 1.170-14.681), demonstrating its signif icant association with HCC(P = 0.028). Conclusion: The mutations in the RT domain of HBV-P gene are associated with the tumorigenesis of HCC.

Background and purpose: It was reported that G1896A and G1899A mutation in the hepatitis B virus(HBV) precore region were all signifi cantly associated with hepatocellular carcinoma(HCC). Simple, sensitive and reliable methods to detect precore mutations are needed in order to prevent the occurrence of HCC in clinical detection. The aim of this study was to develop a simple and sensitive reverse hybridization method for the detection of HBV precore mutation in HBV carriers. This method was applied for exploring the relationship between the precore mutations and HCC in patients of Qidong, Jiangsu Province. Methods: The specifi c probes of nt.1896 and nt.1899 were designed and synthesized. In order to improve the sensitivity and specificity, reaction conditions of reverse hybridization were optimized. We used reverse hybridization to detect 50 HCC serum samples and compared the results with direct sequencing. Then we used this method to assess the association between HBV precore mutations and HCC in serum samples from 50 HCC patients and 50 non-HCC controls. Results: The detection limit of reverse hybridization for HBV DNA level was 103 copy/mL and the sensitivity was 10% within a mixed virus population. The coincidence rate of reverse hybridization analysis was 98% compared with the direct sequencing results. It was showed that G1899A mutation was signifi cantly associated with HCC compared to non-HCC controls(P=0.000, OR=4.846, 95%CI: 2.240-10.485), while G1896A mutation was not associated with HCC. Conclusion: Reverse hybridization is a simple andaccurate approach for the detection of low amounts of HBV precore mutants among a mixed viral population. It has potential usage in the large-scale screening of precore mutations in chronic hepatitis B carriers.

This paper reports the strategies for prevention and control of liver cancer formed in the practice in Qidong field for liver cancer research, and the comprehensive measures aiming at the major risk factors in the past decades. The efficacy of these interventions is reflected in the substantial decrease in the rates of incidence and mortality of liver cancer in Qidong: the age-standardized rate of incidence rate is decreased by 44.35%, and the age-standardized rate of mortality is decreased by 44.20%, especially in younger population. These data are evidenced from the points of views in epidemiology, ecology, and biomarkers monitoring. The long-run profitability in the first prevention and secondary prevention can be benifited from the comprehensive control and intervention strategies in Qidong. DOI:10.3781/j.issn.1000-7431.2014.19.596

OBJECTIVE: To study the relationship between aflatoxin(AF) exposure and primary liver cancer(PLC) among HBsAg carriers.METHODS: A 23-year prospective study was carried out in a cohort of 148 PLC high-risk incidence with Hepatitis B virus(HBV) infection in PLC high prevalence region.RESULTS: 1) The PLC year-incidence in AF exposure group was 2 763.96/100 000(33/1 193.94),significantly higher than that of non-AF exposure group(15/1 283.75,1 168.45/100 000 person-years,P=0.004,RR=2.37,95%CI=1.29-4.33).There were no significant differences between the incidences of other tumours in the two groups(P=0.597).2)In the AF exposure group,14.38%(161/1 120) participants had been detected abnormal serum alanine aminotransferase(ALT),and 50.63%(40/1 120) of those showed abnormal ALT more than two times,significantly higher than that of non-AF exposure group(102/1 109,9.20%,P=0.000;23/1 109,33.33%,P=0.034).In ALT abnormal participants 75.71%(53/70) were positive for urine AFM1,and 68.57%(48/70) of those were more than 10 ng,significantly higher than that of non-AF exposure group(33.33%,26/78,P=0.000;29.49%,23/78,P=0.000).3)In the AF exposure group,6.61%(74/1 120),participants were detected abnormal serum α-fetoprotein(AFP) and 25.32%(20/1 120) of those showed abnormal AFP more than two times,significantly higher than that of non-AF exposure group(4.15%,46/1 109,P=0.010;11.59%,8/1 109,P=0.033).4)The hepatitis C virus(HCV) positivity was 2.03%(3/148) in HBsAg carriers.There were no significance differences of personal life history,tobacco and alcohol absorbing between AF exposure group and AF unexposure group,or HCC group and non-HCC group(P0.05).CONCLUSIONS: AF exposure obviously increased the PLC incidence in HBV carriers,promote their liver damage.Resistance to hepatitis B and AF pollution are useful to prevent PLC development.

OBJECTIVETo explore the relationship between serum HBV DNA load and hepatocellular carcinogenesis in Qidong HBsAg carriers.METHODSIn 1997, 477 HBsAg carriers and 477 age, gender and residence matched HBsAg negative controls were enrolled as a prospective cohort in Qidong city. The entry serum samples were detected for the levels of HBeAg and HBV DNA. The relationship between baseline HBV DNA load and hepatocellular carcinoma (HCC) during the follow-up period from June 1997 to June 2011 were analyzed.RESULTSThe total observed person-years (PY) were 12 200. Eighty-seven patients developed HCC with an incidence of 1498/100 000 PY in the HBsAg positive group versus 6 with an incidence of 94/100 000 PY (P = 0.000) in the HBsAg negative group. The relative risk (RR) was 15.96. N o significant difference existed between the incidences of other tumors in two groups (P = 0.161). Compared with the HBsAg negative group, the RR of HCC was 11.38 (95%CI 4.87 - 26.62, P < 0.01)in the HBsAg+/HBeAg- group and 29.08 (95%CI 12.37 - 68.37, P < 0.01) in the HBsAg+/HBeAg+ group; 5.80 (95%CI 2.29 - 14.70, P < 0.01) in the HBsAg+/HBV DNA- group and 27.75 (95%CI 12.07 - 63.81, P < 0.01) in the HBsAg+/HBV DNA+ group. In HBsAg positive subjects, while the HBV DNA load was classified into 5 levels namely 250 - 10(4), 10(4)-, 10(5)-, 10(6)- and ≥ 10(7) copies/ml, the relative risks for HCC at each level were 2.84 (95%CI 1.44 - 5.61, P < 0.01), 5.75 (95%CI 2.77 - 11.95, P < 0.01), 9.05 (95%CI 4.71 - 17.41, P < 0.01), 6.39 (95%CI 2.79 - 14.64, P < 0.01) and 4.35 (95%CI 2.21 - 8.56, P < 0.01) respectively versus the < 250 copies/ml group.CONCLUSIONHBV DNA is an important risk predictor of hepatocellular carcinoma. The HBsAg carriers with the serum loads of HBV DNA between 10(5) - 10(6) copies/ml are most likely to present with HCC.

Abstract One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout–derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane, and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12-hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than with GRR beverage. Elimination rates were considerably slower with GRR, allowing for achievement of steady-state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. Cancer Prev Res; 4(3); 384–95. ©2011 AACR.

Objective:To explore the correlation between hepatitis B virus e antigen(HBeAg) and hepatocellular carcinoma(HCC) in residents of Qidong — a high-risk area of HCC in Jiangsu Province,China.Methods:This study included 807 hepatitis B virus surface antigen(HBsAg) carriers and 761 age-and gender-matched HBsAg(-) controls enrolled in a prospective cohort in Qidong during 1992.The relationship between the occurrence of HCC and HBsAg was analyzed during the follow-up period from May 1992 to March 2010.Results:A total of 24 715 person-years(PY) was observed.Of 807 cases in HBsAg-positive group,156 cases had developed HCC,and the incidence rate of HCC was 1 288.83/100 000 PY;while in HBsAg-negative group,9 of 761 cases had developed HCC,and the incidence rate of HCC was 71.37/100 000 PY.The relative risks(RRs) of HCC were 13.25(95% confidence interval:6.67-26.33;P0.001) and 28.05(95% confidence interval:13.87-56.73;P0.001) in HBsAg(+) /HBeAg(-) group and HBsAg(+) /HBeAg(+) group,respectively.In the HBsAg(+) group,the RRs for HCC of the four subgroups(HBeAg titer24,1:24-1:27,1:28-1:212,and212) were 2.55(95% confidence interval:1.54-4.22;P0.001),5.02(95% confidence interval:2.89-8.73;P0.001),1.71(95% confidence interval:0.91-3.18;P0.05),and 1.19(95% confidence interval:0.64-2.23;P0.05) folds higher than that of HBeAg(-) subgroup,respectively.Conclusion:HBeAg is an essential predictive factor for the development of HCC.The patients with low titers of HBeAg are at a high-risk of HCC.

OBJECTIVE:To study the relationship between aflatoxin exposure and the development of primary liver cancer (PLC) in patients with chronic hepatitis.METHODS:A 21-year longitudinal study was carried out in a large cohort of 515 PLC high-risk individuals with HBV infection in PLC high prevalence region.RESULTS:(1) The PLC year-incidence of cohort was 1437.25/100,000. And it was significantly higher than that of the same natural peoples (184. 53/100,000, P = 0.000, RR = 7.79). There was no significant difference in the incidence of other tumors between these two groups (P = 0.576). (2) The PLC patients in the cohort were diagnosed at an average age 1.4 year younger than those in the same natural peoples and had an average survival of 6.42 months longer than the latter. (3) The PLC year-incidence of those with the exposure to aflatoxin was significantly higher than that of unexposed people (2784. 96/100,000 vs. 1251.02/100,000, P = 0.008, RR = 2.23). There was no relationship between the incidence rate of other tumors and the aflatoxin exposure. (4) The PLC year-incidence of aflatoxin-exposing people increased with the rising urine excretion of AFM1. When the urine excretion of AFM1 was more than 100 ng during 24 hours, the PLC year-incidence was high as 4717.82/100,000. The urine excretion of AFM1 was also obviously related with the abnormal liver function (P = 0.035). There was no relationship with the positive rate of HBeAg (P = 0.812). (5) The PLC year-incidence of those with the exposure to aflatoxin were infected with HBV (2 784. 96/100 000) significantly higher than that of cohort people (P = 0.001) and the same natural peoples (P = 0.000, RR = 15.09). (6) It took an average time of 14.65 years (median 13.68) from hepatitis occurrence to PLC diagnosis and 7.38 years (median 6.40) from liver cirrhosis to PLC diagnosis.CONCLUSION:HBV infection is a main etiological factor of PLC and the aflatoxin exposure has obvious synergistic effect in the carcinogenesis of PLC. Regular observation in a PLC high-risk cohort is effective for an early diagnosis and treatment. Hepatitis control and aflatoxin de-pollution is effective to inhibit the occurrence of PLC.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

To investigate the relationship between the MMP activities and metastatic ability in human lung adenocarcinoma cell lines with differential metastatic potential.Nine lung adenocarcinoma cell lines were tested for their MMP activities by zymographic analysis methods.The MMP production capabilities of carcinoma cells rose following the increase of their metastatic potentials.The result suggested that there was some relationship between MMP－9 activties and metastatic potential in human lung adenocarcinomas.

In 1995, 234 adults from Qidong, People's Republic of China, were enrolled and followed in a Phase IIa 4-methyl-5-(N-2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) chemoprevention trial. Residents of this area are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods. The intervention was a randomized, placebo-controlled, double-blind study. Elements of the study design and clinical outcomes have been recently published (Jacobson et al, Cancer Epidemiol. Biomark. Prev., 6: 257-265, 1997). The primary objective was to conduct a preliminary assessment of the ability of oltipraz to modulate levels of a validated biomarker of aflatoxin exposure and of the risk of hepatocellular carcinoma by determining levels of aflatoxin-albumin adducts in sera. Healthy eligible individuals were randomized into three arms to receive p.o. 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo for 8 weeks. There were no consistent changes in biomarker levels in the placebo arm over the 16-week observation period, nor was any apparent effect observed in the arm receiving 125 mg of oltipraz each day. However, individuals receiving 500 mg of oltipraz once a week for 8 weeks showed a triphasic response to oltipraz. No effect was observed during the 1st month of the intervention, whereas a significant (P = 0.001) diminution in adduct levels was observed during the 2nd month of active intervention and during the lst month of follow-up. A partial rebound in adduct levels toward baseline values was observed during the 2nd month postintervention. Linear regression models up to week 13 confirmed a significant (P = 0.008) weekly decline of biomarker levels in the group receiving 500 mg of oltipraz once a week. However, despite these effects relative to baseline values within the 500-mg weekly arm, there were no statistically significant differences in biomarker trajectories between treatment arms. The genotype for glutathione S-transferase M1, an oltipraz-inducible isoform involved in the detoxification of aflatoxin B1, did not appear to affect either baseline levels or rates of decline in the biomarker. A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term.