Liver cancer mortality over six decades in an epidemic area: what we have learned.

BACKGROUND AND AIMS: Liver cancer is one of the most dominant malignant tumors in the world. The trends of liver cancer mortality over the past six decades have been tracked in the epidemic region of Qidong, China. Using epidemiological tools, we explore the dynamic changes in age-standardized rates to characterize important aspects of liver cancer etiology and prevention. METHODS: Mortality data of liver cancer in Qidong from 1958 to 1971 (death retrospective survey) and from 1972 to 2017 (cancer registration) were tabulated for the crude rate (CR), and age-standardized rate and age-birth cohorts. The average annual percentage change was calculated by the Joinpoint Regression Program. RESULTS: The natural death rate during 1958-2017 decreased from 9‰ to 5.4‰ and then increased to 8‰ as the population aged; cancer mortality rates rose continuously from 57/105 to 240/105. Liver cancer mortality increased from 20/105 to 80/105, and then dropped to less than 52/105 in 2017. Liver cancer deaths in 1972-2017 accounted for 30.53% of all cancers, with a CR of 60.48/105, age-standardized rate China (ASRC) of 34.78/105, and ASRW (world) of 45.71/105. Other key features were the CR for males and females of 91.86/105 and 29.92/105, respectively, with a sex ratio of 3.07:1. Period analysis showed that the ASRs for mortality of the age groups under 54 years old had a significant decreasing trend. Importantly, birth cohort analysis showed that the mortality rate of liver cancer in 40-44, 35-39, 30-34, 25-29, 20-24, 15-19 years cohort decreased considerably, but the rates in 70-74, and 75+ increased. CONCLUSIONS: The crude mortality rate of liver cancer in Qidong has experienced trends from lower to higher levels, and from continued increase at a high plateau to most recently a gradual decline, and a change greatest in younger people. Many years of comprehensive prevention and intervention measures have influenced the decline of the liver cancer epidemic in this area. The reduction of intake levels of aflatoxin might be one of the most significant factors as evidenced by the dramatic decline of exposure biomarkers in this population during the past three decades.

[Distribution Characteristics and Pollution Assessment of Nutrients in Hengshui Lake Sediments].

Considering Hengshui Lake as the research object, the representative surface sediments at eleven points were collected in March 2019, and the morphological distribution characteristics of carbon, nitrogen, and phosphorus nutrients in the lake sediments were analyzed. The results showed that the total organic carbon (TOC) content in Hengshui Lake sediments was 93.226 mg·g-1, which might lead to a higher risk of potential nitrogen source release. The total nitrogen (TN) content was 1.850 mg·g-1, which was a moderate pollution load; the contents of various nitrogen forms and the proportions in TN were Res-N (0.973 mg·g-1, 52.57%) > WAEF-N (0.531 mg·g-1, 28.69%) > SOEF-N (0.208 mg·g-1, 11.23%) > IEF-N 0.088 (mg·g-1, 4.77%) > SAEF-N (0.051 mg·g-1, 2.75%). These results further indicated that the risk of nitrogen release from sediments in Hengshui Lake was relatively high. The content of total phosphorus (TP) was 1.020 mg·g-1 and that of inorganic phosphorus (IP) was 0.839 mg·g-1, accounting for 82.27% of the TP content, which was a moderate pollution load; the average content of various phosphorus forms and the proportions in IP were Ca-P (0.440 mg·g-1, 52.44%) > Res-P (0.200 mg·g-1, 23.84%) > Fe-P and Al-P (0.169 mg·g-1, 20.14%) > NH4Cl-P (0.030 mg·g-1, 3.58%). In general, the risk of phosphorus release from sediments in Hengshui Lake was relatively low. The analysis of C/N, C/P, and N/P characteristics showed that the organic matter in Hengshui Lake sediments mainly originated from terrestrial grasses and sedge plants, and the phosphorus in the sediments was mainly affected by terrestrial input. Correlation analysis showed that the correlation between carbon, nitrogen, and phosphorus in Hengshui Lake sediment was weak, and the sources of the three nutrients might be different; the correlation between each form of phosphorus was stronger than that of each form of nitrogen, and each form of phosphorus had very good homology. The sources of various forms of nitrogen were diverse and complex. The pollution status of the lake area was evaluated by organic index and organic nitrogen. The results showed that the nutrient pollution in Hengshui Lake sediments was serious, reaching the Grade Ⅳ standard. The potential risk of nitrogen in sediments should be taken seriously and effectively controlled.

Dose-dependent detoxication of the airborne pollutant benzene in a randomized trial of broccoli sprout beverage 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 µmol, 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 ∼25 µmol sulforaphane metabolites per day, and it portends a practical and frugal population-based strategy to attenuate associated long-term health risks of air pollution. This trial was registered at clinicaltrials.gov as NCT02656420.

Cancer survival in Qidong between 1972 and 2011: A population-based analysis.

Population-based cancer survival is an improved index for evaluating the overall efficiency of cancer health services in a given region. The current study analysed the observed survival and relative survival of leading cancer sites from a population-based cancer registry between 1972 and 2011 in Qidong, China. A total of 92,780 incident cases with cancer were registered and followed-up for survival status. The main sites of the cancer types, based on the rank order of incidence, were the liver, stomach, lung, colon and rectum, oesophagus, breast, pancreas, leukaemia, brain and central nervous system (B and CNS), bladder, blood [non-Hodgkin's lymphoma (NHL)] and cervix. For all malignancies combined, the 5-year observed survival was 13.18% and the relative survival was 15.80%. Females had higher observed survival and relative survival (19.32 and 22.71%, respectively) compared with males (9.63 and 11.68%, respectively). The cancer sites with the highest five-year relative survival rates were the female breast, bladder, cervix and colon and rectum; followed by NHL, stomach, B and CNS cancer and leukaemia. The poorest survival rates were cancers of oesophagus, lung, pancreas and liver. Higher survival rates were observed in younger patients compared with older patients. Cancers of the oesophagus, female breast and bladder were associated with higher survival in middle-aged groups. Improved survival rates in the most recent two 5-year calendar periods were identified for stomach, lung, colon and rectum, oesophagus, female breast and bladder cancer, as well as leukaemia and NHL. The observations of the current study provide the opportunity for evaluation of the survival outcomes of frequent cancer sites that reflects the changes and improvement in a rural area in China.

A colorimetric and fluorescent cyanide chemosensor based on dicyanovinyl derivatives: utilization of the mechanism of intramolecular charge transfer blocking.

Chemosensor (CS1) was designed and synthesized by simple green chemistry procedure. CS1 exhibited both colorimetric and fluorescence turn-off responses for cyanide (CN(-)) ion in aqueous solution. The probe showed an immediate visible color changes from yellow to colorless and green fluorescence disappearance when CN(-) was added. The mechanism of chemosensor reaction with CN(-) was studied using (1)HH NMR and (13)C NMR spectroscopies and mass spectrometry. Moreover, test strips based on the sensor were fabricated, which served as convenient and efficient CN(-) test kits.

[Dissolved organic matter release of Zizania caduciflora and Phragmites australis from Lake Dianchi].

Ground dry leaves of two emerged macrophytes Zinania Caduciflora and Phragmites australis from Lake Dianchi were soaked in distilled water in laboratory to track their DOM release process. The results showed that: (1) during soaking, concentration of DOM which was released to the overlying water by the two species increased at first, then decreased and increased again at last. Concentrations of DOC, DON, and DOP released by both species reached their peaks at the 8th, 8th, and 24th hour, respectively; (2) the two species showed the same DOM release trend, i.e., release rates and intensities of DOC, DON, and DOP by both species reached the peaks at the 8th hour, and for both of them, the release rates and intensities of DOC, DON, and DOP at the 8th hour followed the order of DOC > DON > DOP; (3) the SUVA254 value obtained by the UV-visible spectroscopy increased at first and then decreased; (4) Fourier transform infrared (FT-IR) spectroscopy showed that the characteristic peak -OH disappeared during the decomposition process; (5) intensity of the humic-acid fluorescence peak as showed by the 3D-EEM fluorescence intensity (F/DOC) increased along with degradation.

[Retrospective observation of dynamic levels of serum Golgi protein 73 in patients prior to the onset of liver cancer].

OBJECTIVE: To observe the dynamic levels of serum Golgi protein 73(GP73) in patients prior to and after the onset of liver cancer, and to explore the related factors. METHODS: From 2007 to 2012, a periodical screening program was carried out in a group of high risk population with positive Hepatitis B surface antigens (HBsAg) , twice a year. Their serum specimens from every screening time point were kept in Qidong Biobank until liver cancer was diagnosed. Thirty-nine patients with liver cancer were recruited for the study, each of them at least had three times of specimens collected as well as B ultrasound scan (BUS) exam results at onset of disease and within 30 months before diagnosed, amongst 6 time points. In total, there were 162 specimens collected to test GP73 by double-antibody sandwich enzyme-linked immuno-sorbent assay (ELISA). Statistical analyses of time series and differences among groups were performed by stata software 10. RESULTS: The average value of 39 patient's GP73 at the time point of liver cancer onset was (126.77 ± 73.73) µg/L, while the values at the other five time points prior to the onset were (128.32 ± 81.18) , (129.97 ± 83.62) , (127.38 ± 80.10) , (135.52 ± 97.88) and (138.24 ± 93.58) µg/L, respectively, with no significant difference (F = 0.07, P = 0.997). No obvious changing trends of GP73 were observed among the 39 liver cancer cases at the 6 time points. All 162 samples were divided into two groups: without hepatic cirrhosis (63 samples) and with cirrhosis (99 samples) according to findings of B-ultrasonic wave; whose average GP73 values were separately (97.16 ± 51.39) and (151.20 ± 91.68) µg/L. The difference showed statistical significance (F = 18.22, P < 0.01). Furthermore, if we grouped the samples by the average value of GP73 at 130.19 µg/L, then there were only 1/14 of the subjects without hepatic cirrhosis having higher GP73 values, but 12 of the 25 subjects with hepatic cirrhosis having higher GP73 values. The difference showed statistical significance (P = 0.013). The results of Linear regression model also showed that there was no correlation between GP73 and time series (t = 0.75, P = 0.455), but significant correlation between GP73 and hepatic cirrhosis (t = 4.30, P < 0.01). CONCLUSION: No significant changes of the dynamic levels of GP73 could be found among the liver cancer patients within 30 months prior to the onset of disease. GP73 values of the patients with liver cancer may depend on their background of hepatic diseases; and hepatic cirrhosis might be one of the main influencing factors or confounding factors.

[Quantitative analysis of protein concentration by absorption peak integration method of UV spectroscopy--taking alkaline phosphatase as an example].

Adsorption of alkaline phosphatase (APase) on minerals (goethite, montmorillonite) and sediments from Taihu Lake was studied. However, the concentration of alkaline phosphatase in the supernatant cannot be analyzed by the adsorption at 280 nm due to that the UV spectroscopy was changed. Quantitative analysis of alkaline phosphatase in the supernatant by the absorption peak (252-305 nm) integration method of UV spectroscopy was developed. This method determined the concentrations of alkaline phosphatase well. Compared to the results of Bradford, the absorption peak integration method can determine the concentrations of supernatant fast, conveniently, and accurately. This method can also be applied to other protein solution analysis and similar experiments. The drawbacks of traditional single wavelength method (280nm) were overcome to some extent based on the method of absorption peak integration.

Reduced aflatoxin exposure presages decline in liver cancer mortality in an endemic region of China.

Primary liver cancer (PLC) is the third leading cause of cancer mortality globally. In endemic areas of sub-Saharan Africa and Asia, PLC largely arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Although synergistic interactions between these two risk factors have been observed in cohort studies in China, here we determined the impact of agricultural reforms in the 1980s leading to diminished maize consumption and implementation of subsidized universal vaccination against HBV in the 2000s on PLC primary prevention. A population-based cancer registry was used to track PLC mortality in Qidong, China and was compared with the timeline of HBV immunization. Randomly selected serum samples from archived cohort collections from the 1980s to present were analyzed for aflatoxin biomarkers. More than 50% reductions in PLC mortality rates occurred across birth cohorts from the 1960s to the 1980s for Qidongese less than 35 years of age although all were born before universal vaccination of newborns. Median levels of the aflatoxin biomarker decreased from 19.3 pg/mg albumin in 1989 to undetectable (<0.5 pg/mg) by 2009. A population attributable benefit of 65% for reduced PLC mortality was estimated from a government-facilitated switch of dietary staple from maize to rice; 83% of this benefit was in those infected with HBV. Food policy reforms in China resulted in a dramatic decrease in aflatoxin exposure, which, independent of HBV vaccination, reduced liver cancer risk. The extensive HBV vaccine coverage now in place augurs even greater risk reductions in the future.

[Survey of the serum hepatocellular carcinoma marker Golgi glycoprotein (GP73) among Qidong residents and correlation analysis to outcome at two-year follow-up].

OBJECTIVE: To survey the levels of Golgi glycoprotein (GP73), a hepatocellular carcinoma (HCC) marker, in residents of Qidong and determine the correlation of detected GP73 concentration ranges with outcome at two-year follow-up. METHODS: A total of 12,378 individuals (age range: 35-69 years old) from Qidong were enrolled in the study. All participants were tested for hepatitis B virus (HBV) by detecting hepatitis B surface antigen (HBsAg) in serum. One-tenth of the participants were assigned to a stratified-random sample group (those with identification numbers ending with "0") to represent a "subgroup of the natural population" (HBsAgPop, n = 1227). All HBsAg carriers were stratified as a "subgroup of positivity" (HBsAgPve, n = 1025). One-tenth of all HBsAg-negative individuals were assigned to a stratified-random sample group to represent a "subgroup of negativity" (HBsAgNve, n = 1132). Enzyme-linked immunoassay was used to measure the serum GP73 and alpha-fetoprotein (AFP) levels; the distribution, medians (50th percentile), and 95th percentiles of GP73 were determined for the three subgroups. A two-year follow-up was carried out to observe the differential incidence of HCC between the HBsAgPve and HBsAgNve subgroups. RESULTS: A positively skewed distribution of the GP73 values was observed for all three subgroups. The medians for HBsAgPve, HBsAgNve, and HBsAgPop were 67 mug/L, 54 mug/L, and 55 mug/L; the 95th percentiles were 174 mug/L, 108 mug/L, and 114 mug/L, respectively. The AFP positivity rates were 7.23% (37/512) for carriers whose GP73 values were above the median level and 0.78% (4/513) for carriers with GP73 values below the median level, with a highly significant difference between the two (P less than 0.01). A the two-year follow-up, 23 (4.49%) of the 512 carriers with GP73 more than or equal to 67 mug/L had developed HCC, while only one patient (0.19%) of the 513 carriers with GP73 less than 67 mug/L developed HCC, which yielded a relative risk value of 23.6. In the non-carriers, no HCC cases had occurred, regardless of serum GP73 level. CONCLUSION: Serum GP73 has a higher potential as a diagnostic/prognostic marker of HCC in individuals with HBsAg positivity. In follow-up of HBsAg carriers, GP73 may help in the early detection of liver cancer.

[Trends in the mortality of liver cancer in Qidong, China: an analysis of fifty years].

OBJECTIVE: To describe and analyze the charecteristics and trends of liver cancer mortality during the past fifty years in Qidong, China. METHODS: Retrospective mortality survey was conducted to get the data on liver cancer death in the period of 1958-1971, and the data from 1972 to 2007 were obtained from the records of cancer registration in Qidong. The crude mortality rate (CR) of liver cancer, and age-standardized rate by Chinese population (CASR) and by world population (WASR) were calculated and analyzed. The total percent changes (PC) and annual percent changes (APC) were used for evaluating the increasing trends of the mortality. The sex-specific rate, age-specific rate, truncated rate of the age group 35 - 64, cumulative rate of the age group 0-74, cumulative risk, period-rate, and the rate for age-birth cohort were compared. RESULTS: The natural death rate in Qidong residents for the past five-decade period experienced a wave interval of 8.62‰ in 1958 down to 5.37‰ in 1979, and up to 7.75‰ in 2007. The mortality rate for all-site cancers was increased from 56.69 per 100, 000 to 234.97 per 100, 000. The mortality rate of liver cancer, being 20.45 per 100, 100 in 1958 was increased to 49.04 per 100, 000 in 1972, and up to 69.29 per 100, 000 in 2007. According to the registration data of 1972 - 2007, the death from liver cancer was accounted for 34.88% of all deaths due to cancers, with a CR of 58.86 per 100, 000, CASR of 38.36 per 100, 000, and WASR, 49.37 Per 100, 000 in Qidong. The truncated rate for the age group 35 - 64 was 117.08 per 100, 000, and the cumulative rate for the age group 0-74 and the cumulative risk were 5.15% and 5.02%, respectively. The CRs for males was 90.52 per 100, 000 and for females was 27.93 per 100, 000, with a sex ratio of 3.24:1. For the period of 1972 - 2007, the PC for CR was 49.71%, and APC was +1.41%, showing an increasing variation tendency. The APCs for CASR and WASR, however, were decreasing, with a percentage of -1.11%, and -0.84%, respectively. The age-specific mortality rates by period showed a decreasing trend for those under age of 44. Moreover, age-birth cohort analysis showed a more rapid lowering mortality in the age groups 35-, 30-, 25-, and 15-, that is, those born after 1950's. CONCLUSIONS: Liver cancer remains the leading death cause due to cancers in Qidong, with a continuing higher crude mortality rate. Yet the age-standardized mortality rate has presented a declining posture. The liver cancer mortality in young people in Qidong demonstrates a continuously falling trend. The campaign for the control of liver cancer in Qidong has achieved initial success.

Predictive power of hepatitis B 1762T/1764A mutations in plasma for hepatocellular carcinoma risk in Qidong, China.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with nearly 700,000 deaths occurring annually. Hepatitis B virus (HBV) is a major contributor to HCC and acquired mutations in the HBV genome may accelerate its pathogenesis. In this study, a matched case-control investigation of 345 men who died of HCC and 625 controls were nested within a cohort of male hepatitis B surface antigen (HBsAg) carriers from Qidong, China. Matched preserving odds ratios (ORs) were used as a measure of association and 95% confidence intervals (CIs) as a measure of precision. Real-time polymerase chain reaction allowed for a quantitative comparison of the levels of the HBV 1762(T)/1764(A) mutation in cases and controls. A total of 278 (81%) of the cases were positive for the HBV 1762(T)/1764(A) mutation compared with 250 (40%) of the controls. The matched preserving OR of 6.72 (95% CI: 4.66 to 9.68) strongly indicated that cases were significantly more probably than controls to have the mutation. Plasma levels of DNA harboring the HBV mutation were on average 15-fold higher in cases compared with controls (P < 0.001). Most strikingly, the level of the mutation in the 20 controls who later developed and died of HCC were on average 274-fold higher than controls who did not develop HCC. Thus, within this cohort of HBsAg carriers at high risk of developing HCC, individuals positive for the HBV 1762(T)/1764(A) mutation at enrollment were substantially more probably to subsequently develop HCC, with a higher concentration of the mutation in plasma enhancing predisposition for cancer development.

Bioavailability of Sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China.

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.

[A thirty-one year prospective follow-up program on the HBsAg carrier state and primary liver cancer in Qidong, China].

OBJECTIVE: To study the relationship between hepatitis B virus (HBV) and primary liver cancer (PLC), and to assess the outcome of PLC in the carriers of HBsAg. METHODS: General population over age of 15 from a community in Qidong was screened for HBsAg, anti-HBs, and alanine transaminase (ALT) in 1976, and followed-up thenceforth. From January 1, 1977 through December 31, 2007, 12 351 people were enrolled in the cohort, and their occurrence, outcome of PLC and other cancers, together with all the withdrawals due to death were linked to and checked with database from Qidong Cancer Registry and Qidong Vital Registry programs. RESULTS: The total observed person-years (PYs) were 355 305.0. One hundred and seventy-three PLC cases were identified among the HBsAg carriers, with an incidence of 361.55 per 100 000 PYs, while PLC cases were only 95 for the non-carriers, with an incidence of 30.90 per 100 000 PYs. The overall relative risk (RR) was 11.70 (95%CI: 9.06 - 15.19), with RR 12.30 for men and 10.46 for women. HBsAg carriers had high incidence at each age group, compared with the non-carriers for both men and women. Data from cross-over analysis showed that the incidence rates of PLC for the sub-cohorts of female non-carriers, male non-carriers, female carriers, and male carriers were 1.00, 3.07, 10.46, and 37.76, respectively. The cumulative rates of PLC in the 4 groups were 0.86%, 2.73%, 10.22%, and 34.19%, respectively. Results from non-conditional logistic regression model showed that the gender (male), age, HBsAg(+), and ALT(+) were risk factors for the development of PLC while anti-HBs(+) demonstrated a protective effect. No relationship was found among carriers and non-carriers for cancer sites such as lung, stomach, esophagus, intestine, pancreas, breast, cervix, bladder, and lymphoma, brain tumor, or leukemia. CONCLUSION: Causation and its strength, together with specificity and persistency of the association were confirmed from this HBsAg-related cohort study in the general population in Qidong. Intervention measures on HBV should be highlighted for the control of PLC among the HBV infected individuals.

[The patterns of cancer incidence during 1972-2005 in Qidong, China].

OBJECTIVE: To explore the patterns of cancer incidence from 1972 to 2005 in Qidong, Jiangsu province. METHODS: A population-based cancer registration system was established in Qidong region with 1.1 millions residents to collect data of cancer incident cases. 70,646 cases were registered during the years from 1972 to 2005, and ICD-10 was administrated for classification and coding, and crude rate (CR) and age-standardized rate (ASR), percent change (PC), annual percent change (APC) were calculated using annual data on population size. Changes within age-groups for different periods of incidence, and for different years of birth (birth cohort) for the leading sites of cancers were analyzed. RESULTS: The average annual incidence for cancers during the years of 1972-2005 was 184.77 per 100,000 (ASR: 109.32 per 100,000), of which, the incidence for male was 239.22 (ASR: 136.08), and 131.58 (ASR: 79.26) per 100,000 for female. The cumulative risk of cancer occurrence was 16.31% (21.62% in males, and 11.11% in females). The most common leading sites in rank in this area were liver (CR: 60.69 per 100,000), stomach (32.97), lung (27.59), oesophagus (9.34), rectum (8.06), breast (6.48), pancreas (5.97), leukaemia (3.84), bran and CNS (3.43), and colon (2.93). Female breast cancer (12.59) and cervix cancer (4.62) were the forth and the eighth in rank among all sites for women. Liver cancer accounted for almost one third (32.84) of the malignancies. Furthermore, the cancers from digestive organs accounted for 65.85% of all sites. CR rates were rising overall, at 87.19% for PC, and at 1.85% for APC. The ASR, however, reduced by 12.14% for PC, and by 0.51% for APC. The rising trends were also observed for the ASR from cancers in lung, female breast, and colon-rectum, while the decreasing trends were observed for stomach and oesophagus cancer. Birth cohort analysis showed that there was a decline in ages under 35 for the incidence of liver cancer, in ages over 40 for stomach cancer, and in those aged over 45 for bladder cancer and over 50 for oesophagus cancer. Rising trends existed for incidence rates from lung cancer in the aged over 30, pancreas cancer in aged 45-59, and female breast cancer in those aged 40 and above. CONCLUSION: Monitoring of cancer incidence rates through population-based cancer registration in 34 years did help to show the burden and patterns of main cancer sites and time trends, which provides some references to future aetiological study, and policy making on cancer control in Qidong.

Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometry.

Liver cancer is the leading cause of cancer death in many regions of the world. With the goal to discover biomarkers that reflect subsets of high-risk individuals and their prognosis, we nested our study in a male cohort of 5,581 hepatitis B surface antigen carriers in Qidong, People's Republic of China, who were recruited starting in 1989. By December 2003, 667 liver cancer cases were diagnosed in this group and plasma samples collected at the initial screening at enrollment were available in 515 cases who had succumbed to liver cancer. Hepatitis B virus (HBV) DNA could be isolated in 355 (69%) of these samples. In 14%, 15%, 19%, 31%, and 22%, screening took place at < or = 1.5, 1.51 to 3, 3.01 to 5, 5.01 to 9, and > 9 years before death, respectively; and 39% died at age below 45 years. The relation between mutations in HBV and time to death were determined by logistic regression for the odds of mutation and by survival analyses methods with age as the time scale. In 279 (79%) of these individuals, the samples contained a two-nucleotide 1762T/1764A HBV mutation. Sixteen samples lacking the 1762T/1764A mutation had novel mutations elsewhere in the 1761 to 1767 region of the HBV genome. There was a statistically significant difference (P = 0.012) for the high prevalence of the HBV mutations in the men who died from hepatocellular carcinoma under the age of 45 years relative to those who died after 55 years of age and HBV mutations accelerated death (relative hazard, 1.40; 95% confidence interval, 1.06-1.85) and that the effect was attenuated by age from 2.04 for age 35 years to 1.0 for age 65 years with the 90% confidence band being above 1 for ages < 50 years. These findings provide a conceptual framework to explain the acceleration of mortality in individuals infected with HBV.

Trends in the incidence of cancer in Qidong, China, 1978-2002.

A population-based cancer registry was established in Qidong, Jiangsu Province, China, in 1972, and the trends in incidence rates of the major cancer sites have been analyzed for a 25-year period, 1978-2002. Five-year age-specific rates, crude incidence rates, world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual data on population size, and estimates of its age structure. The indices of histological verification of diagnosis, death certificate only and proportion of mortality to incidence were employed for assessing the registration quality. A total of 51,933 incident cases of cancer were registered in Qidong from years 1978 to 2002, with a male-to-female sex ratio of 1.9:1. Crude incidence increased markedly over the 25-year period (PC and APC of +55.6% and +2.1%, respectively), but ASR showed a slight decrease (-0.4% in males, and -0.3% in females), indicating that the major part of this is due to population ageing. The leading cancer sites in rank were liver (average ASR = 50.8 per 100,000), stomach (26.7), lung (22.7), colon-rectum (8.9), oesophagus (7.4) and breast (5.4). Cancers of liver, lung, colon-rectum and female breast all showed increases in incidence during the study period, with APCs (ASR) of +0.1%, +1.7% and +1.4% for males, and +0.2%, +0.9%, +1.9% and +1.1% for females, while the cancers of stomach (APC: -3.2% in male, and --2.4% in female) and cervix (APC: -4.7%) showed notable declines. Examination of age-specific rates showed declining trends in the younger generations for liver cancer, but increases for cervix cancer. The results underline the increasing importance of cancer as a cause of mortality and morbidity in a population that is ageing and undergoing profound changes in socioeconomic development and lifestyle. The cancers of high lethality that have been common in the Chinese population (liver, stomach, oesophagus) are showing some evidence of decline, at least in younger generations, but they remain major problems. At the same time, the cancers associated with economically "developed" societies -- lung, colon-rectum and female breast -- are showing increases. The population-based cancer registry is an indispensable tool for providing data for planning and evaluation of programmes for cancer control in all societies.

[Evaluation of secular trend of liver cancer incidence in Qidong, Jiangsu province, 1973-2002].

OBJECTIVE: To evaluate the secular trend of liver cancer incidence 1973-2002 in Qidong, a high-prevalent area in Jiangsu province. METHODS: The population-based cancer registration data collected during the period of 1973-2002 were used to calculate the crude rate (CR), world age-standardized rate (WASR), five-year age-specific rate, truncated rate of those aged 35-64, cumulative rates of those aged 0-64 and 0-74, percent change (PC), and annual percent change (APC). The incidence rates by age, period/age, and cohort/age were analyzed and compared. RESULTS: The CR was 59.28 per 100,000 on average; and was 91.65 per 100,000 for males and 27.64 per 100,000 for females, with a sex ratio of 3.32:1. The WASR was 58.71 per 100,000 on average; and was 93.32 per 100,000 for males and 26.46 per 100,000 for the females. The truncated rate and cumulative rate of those aged 0-64 and 0-74 were 143.61 per 100,000 and 4.74% and 6.07% respectively. The PC and the APC were +30.90% and +1.58% for the crude incidence rate, and +12.33% and +0.41% for the age-standardized rate. The incidence data demonstrated a rising trend in general and a decreasing pattern for the age-specific rates under age of 35 by comparing the two 15-year periods. Decline trend also existed for the younger age groups when the time was divided into 6 subperiods. Birth cohort analysis showed notable reducing changes for those born after the year 1963. CONCLUSION: The crude rate of incidence of liver cancer has arisen in general in the past 30 years in Qidong area, which may reflects the increase of middle-aged and elderly populations. Many years' comprehensive prevention measures taken in the area, however, have been and will continue to be effective on the decrease of the incidence of liver cancer among the younger generations.

Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods, and are exposed to high levels of phenanthrene, a sentinel of hydrocarbon air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens. Glucoraphanin, the principal glucosinolate in broccoli sprouts, can be hydrolyzed by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication enzymes. In a randomized, placebo-controlled chemoprevention trial, we tested whether drinking hot water infusions of 3-day-old broccoli sprouts, containing defined concentrations of glucosinolates, could alter the disposition of aflatoxin and phenanthrene. Two hundred healthy adults drank infusions containing either 400 or < 3 micromol glucoraphanin nightly for 2 weeks. Adherence to the study protocol was outstanding; no problems with safety or tolerance were noted. Urinary levels of aflatoxin-N(7)-guanine were not different between the two intervention arms (P = 0.68). However, measurement of urinary levels of dithiocarbamates (sulforaphane metabolites) indicated striking interindividual differences in bioavailability. An inverse association was observed for excretion of dithiocarbamates and aflatoxin-DNA adducts (P = 0.002; R = 0.31) in individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti-phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was detected in urine of all participants and showed a robust inverse association with dithiocarbamate levels (P = 0.0001; R = 0.39), although again no overall difference between intervention arms was observed (P = 0.29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions.

Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas.

Hepatocellular carcinoma is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the global incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection. Although pharmacological approaches establish proof of principle and help identify key molecular targets for interventions, food-based approaches that also use these molecular targets may be the most practical for widespread application in high-risk populations.