Activation of p38MAPK in spinal microglia contributes to autologous nucleus pulposus-induced mechanical hyperalgesia in a modified rat model of lumbar disk herniation.

Recent studies have implicated the activation of p38 mitogen-activated protein kinase (MAPK) and glial cells contribute to hyperalgesia following nerve injury or nerve compression. In our work, we investigated the underlying mechanisms of autologous nucleus pulposus (NP)-induced mechanical hyperalgesia in a modified rat model of lumbar disk herniation (LDH). Firstly, our results showed that 50% mechanical withdrawal threshold (50% MWT) decreased on postoperative day (POD) 1 and significantly minimally reduced on POD 7 and lasted for day 28 after surgery (P < 0.05). Secondly, phosphorylation of p38MAPK (p-p38MAPK) and glial cells were monitored on POD 1, 3, 7, 14 and 28 using immunofluorescence staining. P38MAPK activation, observed in the spinal cord, began to increase on POD 1, peaked on POD 3, and significantly decreased on POD 14 and POD 28 (P < 0.05). Microglia activation was initiated at day 1, maximal at day 3, and maintained until day 14 after surgery (P < 0.05). Astrocytic activation was found in 7 to 14 days after modelling (P < 0.05). Then, double immunostaining method was applied to observe the co-expression of p-p38MAPK and glial cells, and it showed that p-p38MAPK was mainly expressed in activated microglia, rarely in neurons, and none in astrocytes. Lastly, we discovered that both SB203580 (50ug, p38MAPK inhibitor) and minocycline (0.5 mg, microglial inhibitor) would inhibit the p-p38MAPK protein expression tested by western blot analysis and reduce mechanical hyperalgesia. In conclusion, current study suggest that activation or phosphorylation of p38MAPK in spinal microglia contributes to autologous NP-induced mechanical hyperalgesia in our animal model.

[Liver cancer epidemiology in China, 2015].

Objective: Using updated population-based cancer registration (PBCR) data, we estimated nation-wide liver cancer statistics overall, by sex and by areas in China. Methods: Qualified PBCR data of liver cancer in 2015 which met the data quality criteria were stratified by geographical locations, sex, and age groups. Age-specific incidence and mortality rates by sex and area were calculated. The burden of liver cancer was evaluated by multiplying these rates by the year of 2015 population. Chinese standard population in 2000 and World Segi's population were used for the calculation of age-standardized rates (ASR) of incidence and mortality. Results: Qualified 368 cancer registries covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were 370 000 new cases (274 000 males and 96 000 females) of liver cancer in China. The age-standardized incidence rates by Chinese standard population (ASR China) and World Segi's population (ASR World) were 17.64 per 100 000 and 17.35 per 100 000, respectively. Rural areas showed higher incidence (ASR China: 20.07 per 100 000, ASR World: 19.67 per 100 000) than urban areas (ASR China: 15.90 per 100 000, ASR world: 15.67 per 100 000). Subgroup analysis showed that western areas of China had highest incidence rate of liver cancer, with the ASR China of 20.65 per 100 000 and 20.22 per 100 000 for ASR world, respectively. For new cases of liver cancer deaths, there were 326 000 new deaths (242 000 males and 84 000 females) in China, with age-standardized mortality rate by Chinese standard population and World Segi's population of 15.33 per 100 000 and 15.09 per 100 000, respectively. Rural areas showed higher mortality (ASR China: 17.17 per 100 000, ASR world: 16.86 per 100 000) than urban areas (ASR China: 14.00 per 100 000, ASR World: 13.81 per 100 000). Conclusions: There is still a heavy burden of liver cancer in China. Rural residents have higher incidence and mortality of liver cancer compared with urban counterparts. It is likely that many factors such as hepatitis virus infection, and aflatoxin exposure play a dominating role. Prevention and control strategies should be enhanced in the future.

[Report of cancer epidemiology in China, 2015].

Objective: Data from local cancer registries were pooled to estimate cancer incidence and mortality in China, 2015. Methods: Data submitted from 501 cancer registries were checked & evaluated according to the criteria of data quality control, and 368 registries' data were qualified for the final analysis. Data were stratified by area (urban/rural), sex, age group and cancer sites, and combined with national population data to estimate cancer incidence and mortality in China, 2015. Chinese population census in 2000 and Segi's population were used for age-standardized. Results: Total population covered by 368 cancer registries were 309 553 499 (148 804 626 in urban and 160 748 873 in rural areas). The percentage of morphologically verified cases (MV) and the percentage of death certificate-only cases (DCO) accounted for 69.34% and 2.09%, respectively, and the mortality to incidence ratio was 0.61. About 3 929 000 new cancer cases were reported in 2015 and the crude incidence rate was 285.83 per 100 000 population (males and females were 305.47 and 265.21 per 100 000 population). Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.64 and 186.39 per 100 000 population, respectively, with the cumulative incidence rate (0-74 age years old) of 21.44%. The cancer incidence and ASIRC were 304.96/100 000 and 196.09/100 000 in urban areas and 261.40/100 000 and 182.70/100 000 in rural areas, respectively. About 2 338 000 cancer deaths were reported in 2015 and the cancer mortality was 170.05/100 000 (210.10/100 000 in males and 128.00/100 000 in females). Age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 106.72/100 000 and 105.84/100 000, respectively, with the cumulative incidence rate (0-74 age years old) of 11.94%. The cancer mortality and ASMRC were 172.61/100 000 and 103.65/100 000 in urban areas and 166.79/100 000 and 110.76/100 000 in rural areas, respectively. The most common cancer cases including lung, gastric, colorectal, liver and female breast, the top 10 cancer incidence accounted for about 76.70% of all cancer new cases. The most common cancer deaths including lung, liver, gastric, esophageal and colorectal, the top 10 cancer deaths accounted for about 83.00% of all cancer deaths. Conclusions: The burden of cancer showed a continuous upward trend in China. Cancer prevention and control faces the problem of the disparity in different areas and different cancer burden between men and women. The cancer pattern in China presents the coexistence of the cancer patterns in developed and developing countries. The situation of cancer prevention and control is still serious in China.

[The incidence and mortality of lung cancer in China, 2014].

Objective: To estimate lung cancer incidence and mortality in China using population-based cancer registry data in 2014 collected by National Central Cancer Registry of China (NCCRC). Methods: 449 cancer registries submitted cancer registry data in 2014. All datasets were evaluated and 339 registries' data which met the quality control criteria of NCCRC were analyzed. Numbers of new lung cancer cases and deaths were estimated using calculated incidence and mortality rates and corresponding national population stratified by areas, sexes and age groups. The standard population of Chinese census in 2000 and world Segi' s population were applied to calculate age-standardized incidence and mortality rates in China and worldwide, respectively. Results: A total of 781, 500 new lung cancer cases were diagnosed in 2014. The crude incidence rate was 57.13 per 100 000 and the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 36.71 per 100 000 and 36.63 per 100 000, respectively. The cumulative incidence rate (0-74 years old) was 4.50%. Lung cancer was the most common cancer in male (ASIRW: 50.04 per 100 000) and the second most common cancer in female (ASIRW: 23.63 per 100 000). The incidence rates were slightly similar in urban areas and in rural areas (ASIRW: 36.64 per 100 000 vs 36.56 per 100 000). A total of 626 400 lung cancer deaths were reported. The crude mortality rate was 45.80 per 100 000 and the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 28.49 per 100 000 and 28.31 per 100 000, respectively. The cumulative mortality rate (0-74 years old) was 3.32%. Lung cancer was the most common cause of cancer deaths both in male (ASMRW: 40.21 per 100 000) and female (ASMRW: 16.88 per 100 000). The mortality rate was slightly higher in rural areas than in urban areas (ASMRW: 28.63 per 100 000 vs 28.04 per 100 000). Both lung cancer incidence and mortality rates increased with age, and the peak age was 80-84 years group. Conclusions: The disease burden of lung cancer is heavy in China. Efficient national health policies and prevention and control strategies against lung cancer should be promoted.

[Incidence and mortality of laryngeal cancer in China, 2014].

Objective: To estimate the incidence and mortality of laryngeal cancer in China based on the cancer registration data in 2014, collected by the National Central Cancer Registry (NCCR), and to provide support data for the control and prevention of laryngeal cancer. Methods: The incident and death data of laryngeal cancer in 2014 from 339 cancer registries met the quality criteria of NCCR, and then adopted for analysis. The incident and death number, crude rate, age standardized rate, truncated rate and proportion which stratified by areas (urban/rural) and age were calculated. The nationwide incidence and mortality of laryngeal cancer in 2014 were estimated by combining with those data on national population in 2014. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: It was estimates that 23.4 thousand new cases of laryngeal cancer occurred in China in 2014. There were 20.8 thousand males and 2.6 thousand females. And 14.5 thousand occurred in urban areas, while 8.9 thousand in rural areas. The age standardized rates of incidence by world standard population (ASRs world) in male, female and both genders were 2.05/100, 000, 0.24/100, 000 and 1.14/100, 000, respectively, whereas those were 1.22/100, 000 and 1.03/100, 000 for urban and rural areas. The incidence was much higher in males than females, and slightly higher in urban areas than those in rural areas. Moreover, it was estimates that 13.2 thousand death cases of laryngeal cancer occurred in China in 2014. There were 11.5 thousand males and 1.7 thousand females. And 7.8 thousand occurred in urban areas, while 5.4 thousand in rural areas. The age standardized rates of mortality by ASRs world in male, female and both genders were 1.08/100, 000, 0.14/100, 000 and 0.60/100, 000, respectively, whereas those were 0.60/100, 000 and 0.59/100, 000 for urban and rural areas. The mortality was much higher in males than females, and slightly higher in urban areas than those in rural areas. In males, the age specific incidence and mortality of laryngeal cancer increased greatly from 40-44 and 45-44 years old, respectively, and peaked at age group of 75-79 and >85 years old. In females, the age specific incidence and mortality increased slowly from 50-54 and 60-64 years old, respectively, and peaked at age group of 80-84 and >85 years old. The trends remained similar in urban and rural areas, except for the different peak ages. Conclusions: The incidence and mortality of laryngeal cancer in China are at middle-low levels worldwide, and there are obvious differences between urban and rural areas with distinct gender disparity. Comprehensive prevention and control strategies should be carried out according to local status and age groups.

[Incidence trend and change in the age distribution of female breast cancer in cancer registration areas of China from 2000 to 2014].

Objective: To estimate the incidence trend and change in the age distribution of female breast cancer in cancer registry areas in China from 2000 to 2014. Methods: 22 cancer registries in China with continuous monitoring data from 2000 to 2014 were selected. All datasets were checked and evaluated based on data quality control criteria and were included in the analysis. The cancer registries covered 675 954 193 person-years, including 342 010 930 person-years of male and 333 943 263 person-years of female. Female breast cancer cases (International Classification of Diseases-10(th) Revision: C50) were extracted. Crude incidence rate (CR), age-standardized incidence rate by Chinese standard population(ASIRC), annual percent change (APC), crude and adjusted mean age at onset were calculated. Incidence rates stratified by regions and age groups were calculated. Results: Female breast cancer incidence rate significantly increased from 31.90/100 000 in 2000 to 63.30/100 000 in 2014. Incidence rate increased rapidly from 2000 to 2008 (CR: APC=6.5%, 95%CI: 5.3%-7.8%; ASIRC: APC=4.6%, 95%CI: 3.6%-5.7%). Its increment slowed down from 2008-2014 (CR: APC=3.2%, 95%CI: 1.4%-5.1%; ASIRC: APC=1.4%, 95%CI:-0.1%-2.9%). The crude mean age at onset increased from 54.4 in 2000 to 57.0 in 2014. Adjusted mean age at onset remained around 54.3 in 2014. Crude mean age at onset increased significantly over time in all registry areas (ß=0.192, P<0.001), urban (ß=0.205, P<0.001) and rural (ß=0.092, P=0.014) areas, while adjusted mean age at onset remained stable in all registry areas (ß=0.009, P=0.289), urban (ß=0.017, P=0.139) and rural (ß=-0.054, P=0.109) areas. Conclusion: Female breast cancer incidence rate in China increased from 2000 to 2014. Aging of the population resulted in a significant increase in crude mean age at onset. After age adjustment, no significant changes in age distribution were found.

[Trend analysis of age of diagnosis for liver cancer in cancer registry areas of China, 2000-2014].

Objective: To investigate trends of mean age of diagnosis for liver cancer during 2000 to 2014, which may provide basic information for making feasible cancer prevention strategies. Methods: Based on the continuous cancer incidence data from 22 cancer registries of China between 1 January 2000 and 31 December 2014, the incidence by birth-cohort (year of birth between 1925 and 1994) and age specific incidence rates were calculated. The incidence of different age groups were also calculated. World Segi's population was used for age standardization. The liner regression model was applied to analyze the changing trend of mean age of diagnosis. Results: In 2014, the incidence rate for population with 80 years older and above was 108.21 per 100 000, whereas the rate for population at 30-39 years old was 5.09 per 100 000. But the mean age of diagnosis for liver cancer showed an increasing trend from 2000 to 2014. For male, it had increased from 58.80 to 62.35 (t=18.70, P<0.001) . For female, it had increased from 64.02 to 68.99 (t=20.50, P<0.001) . After age standardization, the mean age of diagnosis still showed increasing trend. Meanwhile, the proportion of liver cancer in people above 70 years old was 25.05% in 2014, which was higher than that in 2000 (22.49%). Conclusion: The mean age of liver cancer incidence was increasing during 2000-2014.

[Analysis on the trend of prostate cancer incidence and age change in cancer registration areas of China, 2000 to 2014].

Objective: To analyze the trend of cancer incidence and age changes among men in cancer registration areas of China from 2000 and 2014. Methods: We select the information of national cancer registry with continuous data from 2000 to 2014, review and organize the monitoring data at the above registries. A total of 22 monitoring registries were included in this study. The covering population of male were about 314 330 648 person years. The information on the incidence of all male prostate cancer patients with C61 was extracted from the International Classification of Diseases-10(th) Revision (ICD-10). To understand the incidence of male prostate cancer in each year, the age-standardized rate by Chinese population (ASR), average annual percent change (AAPC), adjusted mean age at onset were calculated. Incidence rates stratified by regions and age groups were also calculated. The linear regression model was employed to analyze the relationship between mean age at onset and year. Results: The prostate cancer incidence in China increased by 11.5% (95%CI: 10.3%-12.7%) from 2000(4.62/100 000) to 2014(21.62/100 000), the age-standardized incidence rate increased by 7.1% (95%CI: 6.0%-8.1%) and the growth of rural was greater than that of urban. The age-specific incidence showed that the incidence rate increased significantly among the age group of 50 years; the incidence rates in men who have the same age but with different birth years showed a significant increase as birth years increased. The adjusted mean age at diagnosis of prostate cancer in cancer registry areas was 74.09 years old in the year of 2000, reduced by 0.13 year old to 72.35 years old in 2014 (ß=-0.13, P<0.001). The adjusted mean age at onset declined significantly over time in urban areas (ß=-0.13, P<0.001). Conclusion: The trend of prostate cancer incidence among men in cancer registry regions generally increased, and the average age at diagnosis declined slightly from 2000 to 2014.

[Analysis on the trend of cancer incidence and age change in cancer registry areas of China, 2000 to 2014].

Objective: To analyze the trends of cancer incidence and age changes in China with using cancer registration data, and to provide evidence for the development of cancer prevention and control. Methods: Twenty-two cancer registries with continuous (2000-2014) data were selected. The incidence of different sex and regional population, the standardized incidence rate by Chinese population, the average annual change percentage (AAPC) and annual change percentage(APC) were calculated. Age-period-cohort model were used to analyze the changes of cancer incidence, age-adjusted mean ages. The age-standardized proportion of 2000 and 2014 with were compared. Results: The cancer incidence in China increased by 3.9% (95%CI: 3.7%-4.1%) from 2000 to 2014 in APC, and the age-standardized incidence rate increased by 1.2% (95%CI: 1.0%-1.4%) in AAPC. The age-specific incidence showed that each age groups increased significantly in female, ranged between 0.9% to 6.0%. The APC in male aged from 60 years old showed decline trend, the APC in 60-69, 70-79, ≥80 years old were -0.2, -0.3, -0.3, while in the population aged 0-29, 30-39 years old increased dramatically, APC were 3.5, 2.0. Female under 60 also increased, and APC in 0-29, 30-39, 40-49, 0-59 years old were 5.7, 6.0, 3.4, 2.9, respectively. The mean age of patients diagnosed with cancer were increased during the past 15 years, with about 0.11 years per year increased. However, the mean age of the patients diagnosed with cancer showed decreased trend by 0.13 years after age structure adjusted. Conclusion: The trend of mean age for cancer incidence in China were getting younger than before, and the trend in women is more obviously than in man.

[Incidence and mortality of cervical cancer in China, 2014].

Objective: To estimate the incidence and mortality of cervical cancer in China based on the cancer registry data in 2014, collected by the National Central Cancer Registry (NCCR). Methods: There were 449 cancer registries submitted cervical cancer incidence and deaths in 2014 to NCCR. After evaluating the data quality, 339 registries' data were accepted for analysis and stratified by areas (urban/rural) and age group. Combined with data on national population in 2014, the nationwide incidence and mortality of cervical cancer were estimated. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: Qualified 339 cancer registries covered a total of 288 243 347 populations (144 061 915 in urban and 144 181 432 in rural areas). The percentage of morphologically verified cases and death certificate-only cases were 86.07% and 1.01%, respectively. The mortality to incidence ratio was 0.30. The estimates of new cases were about 102 000 in China in 2014, with a crude incidence rate of 15.30/100 000. The age-standardized incidence rates by China standard population (ASR China) and world standard population (ASR world) of cervical cancer were 11.57/100 000 and 10.61/100 000, respectively. Cumulative incidence rate of cervical cancer in China was 1.11%. The crude and ASR China incidence rates in urban areas were 15.27/100 000 and 11.16/100 000, respectively, whereas those were 15.34/100 000 and 12.14/100 000 in rural areas. The estimates of cervical cancer deaths were about 30 400 in China in 2014, with a crude mortality rate of 4.57/100 000. The ASR China and ASR world mortality rates were 3.12/100 000 and 2.98/100 000, respectively, with a cumulative mortality rate (0-74 years old) of 0.33%. The crude and ASR China mortality rates were 4.44/100 000 and 2.92/100 000 in urban areas, respectively, whereas those were 4.72/100 000 and 3.39/100 000 in rural areas. Conclusions: There is still a heavy burden of cervical cancer in China. The burden and patterns of cervical cancer shows different characters of urban and rural people. Prevention and control strategies should be implemented referring to local status.

[Report of Cancer Incidence and Mortality in China, 2014].

Objective: The registration data of local cancer registries in 2014 were collected by National Central Cancer Registry (NCCR)in 2017 to estimate the cancer incidence and mortality in China. Methods: The data submitted from 449 registries were checked and evaluated, and the data of 339 registries out of them were qualified and selected for the final analysis. Cancer incidence and mortality were stratified by area, gender, age group and cancer type, and combined with the population data of 2014 to estimate cancer incidence and mortality in China. The age composition of standard population of Chinese census in 2000 and Segi's population were used for age-standardized incidence and mortality in China and worldwide, respectively. Results: Total covered population of 339 cancer registries (129 in urban and 210 in rural) in 2014 were 288 243 347 (144 061 915 in urban and 144 181 432 in rural areas). The mortality verified cases (MV%) were 68.01%. Among them, 2.19% cases were identified through death certifications only (DCO%), and the mortality to incidence ratio was 0.61. There were about 3, 804, 000 new cases diagnosed as malignant cancer and 2, 296, 000 cases dead in 2014 in the whole country. The incidence rate was 278.07/100, 000 (males 301.67/100, 000, females 253.29/100, 000) in China, age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 190.63/100, 000 and 186.53/100, 000, respectively, and the cumulative incidence rate (0-74 age years old) was 21.58%. The cancer incidence and ASIRC in urban areas were 302.13/100, 000 and 196.58/100, 000, respectively, whereas in rural areas, those were 248.94/100, 000 and 182.64/100, 000, respectively. The cancer mortality in China was 167.89/100, 000 (207.24/100, 000 in males and 126.54/100, 000 in females), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population were 106.98/100, 000 and 106.09/100, 000, respectively. And the cumulative incidence rate (0-74 age years old) was 12.00%. The cancer mortality and ASMRC in urban areas were 174.34/100, 000 and 103.49/100, 000, respectively, whereas in rural areas, those were 160.07/100, 000 and 111.57/100, 000, respectively. Lung cancer, gastric cancer, colorectal cancer, liver cancer, female breast cancer, esophageal cancer, thyroid cancer, cervical cancer, encephala and pancreas cancer, were the most common cancers in China, accounting for about 77.00% of the new cancer cases. Lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, breast cancer, encephala, leukemia and lymphoma were the leading causes of death and accounted for about 83.36% of cancer deaths. Conclusions: The progression of cancer registry in China develops rapidly in these years, with the coverage of registrations is expanded and the data quality was improved steadily year by year. As the basis of cancer prevention and control program, cancer registry plays an important role in making the medium and long term of anti-cancer strategies in China. As China is still facing the serious cancer burden and the cancer patterns varies differently according to the locations and genders, effective measures and strategies of cancer prevention and control should be implemented based on the practical situation.

[Analysis of cancer incidence and mortality in elderly population in China, 2013].

Objective: To estimate the cancer incidence and mortality in elderly Chinese population in 2013 based on the data from local cancer registries submitted to National Central Cancer Registry (NCCR). Methods: Data from 255 cancer registries submitted to NCCR with qualified data after checked and evaluated, were selected for this estimation. Cancer incidence and mortality were stratified by areas, sex, age groups and cancer site, combined with population data of the year 2013 to estimate cancer epidemiology in older people in China. Chinese population census in 2000 and Segi's population were used for the estimation of age-standardized incidence/mortality rates. Results: All the 255 cancer registries (88 in urban and 167 in rural areas) were selected for this estimation, covered 37 407 728 elderly subjects, accounting for 17.73% of the entire national elderly population. It was estimated about 2 171.0 thousand new cancer cases in older people in China, accounting for 58.96% of all cancer incidence, with the crude incidence rate of 1 029.16/100 000 (1 297.96 per 100 000 in male, 777.18 per 100 000 in female), and the age-standardized incidence rate by Chinese standard population (ASIRC, 2000) was 1 019.25 per 100 000. It was estimated about 1 600.5 thousand deaths in older people in China, accounting for 67.70% of all cancer deaths, with the crude mortality of 758.72/100 000 (988.37 per 100 000 in males, 543.44 per 100 000 in females), and the age-standardized incidence rate by Chinese standard population (ASIRC, 2000) was 730.78 per 100 000. Lung cancer, stomach cancer, colorectal cancer, liver cancer and esophageal cancer were the most common cancers, accounting for about 67.70% of all cancer cases in China. Those cancers are also the most common cancers in China, accounting for about 73.45% of all cancer deaths. Conclusions: The cancer burden of elderly population in China is very serious. The major cancer incidence and mortality in urban and rural areas are similar, but the cancer patterns are very different in urban and rural areas. As cancer burdens for older people are different between urban and rural areas in China, more attention should be paid to the need of older people according to the actual situation.

Quantitative fluorescence image analysis of DNA content and nuclear morphology on esophageal balloon cytology smears and subsequent development of esophageal and gastric cardia cancer in Linxian, China.

The highest incidences of esophageal and gastric cardia cancer in the world occur in northern China. Chinese scientists have developed esophageal balloon cytology screening to detect these cancers, but traditional cytology is sometimes inadequate to find some early, curable lesions. Several studies suggest that quantitative fluorescence image analysis (QFIA) of DNA ploidy and nuclear morphology may be able to improve upon traditional cytology results. In October 1987, esophageal balloon cytology was performed on 1331 adults in Linxian, China, and all samples were evaluated both by traditional cytology and QFIA. From 1987 to May 1991, 62 new squamous esophageal cancers and 44 new adenocarcinomas of the cardia were identified in this cohort. Proportional hazards models were used to evaluate the relationship of cytological diagnoses and six QFIA variables to subsequent cancer risk. These models showed significant trends for increasing esophageal cancer risk, with increasing values in five of the QFIA variables and with increasing severity of the traditional cytological diagnoses. A comparison of models with only cytology variables versus models with both cytology and QFIA variables indicated that the QFIA provided an important additional predictive value. Persons with both cytological dysplasia and high cellular DNA were 8 times more likely to develop esophageal cancer than were individuals with neither of these conditions. For cardia cancer, associations between QFIA variables or cytological diagnoses and later cancer were more limited. This study suggests that the QFIA variables evaluated here are independent predictors of squamous esophageal cancer and that combining QFIA with traditional cytology can improve prediction of esophageal cancer risk.

Volatile N-nitrosamines and their precursors in Chinese salted fish--a possible etological factor for NPC in china.

Epidemiological studies show that the consumption of Chinese salted fish is a causative factor for nasopharyngeal carcinoma (NPC) in southern China. In the present study, N-nitrosamines and their precursors were analyzed in 145 samples of cooked, salted fish collected from various areas in China. The results show that N-dimethylnitrosamine (NDMA), N-diethylnitrosamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) were present in the salted fish. Total volatile N-nitrosamines (TVN) in the salted fish were 0.028 to 4.54 mg/kg. The samples from areas with higher NPC risk showed a higher average level of TVN than those from areas of lower NPC risk. Positive correlations were found between the levels of NDMA, NDEA and TVN and mortality from NPC. Although neither the nitrates nor the nitrites in the salted fish were present at significantly high levels, in vitro data regarding nitrosation of salted fish showed that the N-nitrosamine content had increased substantially. The results support the conclusion that the high NPC risk in southern Chinese may be attributed to consumption of salted fish containing high levels of N-nitrosamines.

[Cytotoxic and transforming activities of salted fish stocks on C3H 10T 1/2 CL8 cells].

Epidemiological case-control study had shown that consumption of salted fish might be a causative factor for human nasopharyngeal carcinoma. In order to test this hypothesis, salted fish extract was studied by C3H 10T 1/2 CL8 cell transformation system. Neither cytotoxicity nor transformation effect was found in the solvent control, but a definite dose-response relation was obtained using relative transformation index when the cells were treated with 0.025-2.000 micrograms/ml 3-methylcholanthrene in the positive control. Current study showed that in the salted fish extract, dose-response relation in cytotoxicity was present in twelve fractions and transformation index significantly increased in five fractions. The maximum relative transformation indices in dichloromethane-methanol, hexane and acetone extract fractions from Murihura croaker were 15.38, 7.69 and 4.29, respectively; and those of dichloromethane-methanol and hexane extract fractions from Sudyoke croaker were 21.69 and 7.69, respectively. In addition, one type-III-focus of cell transformation was found in dichloromethane-methanol fraction and another in acetone fraction of Murihura croaker. In conclusion, there must be more than one carcinogen in the salted fish.

Induction of malignant nasal cavity tumours in Wistar rats fed Chinese salted fish.

Epidemiological evidence has implicated Chinese salted fish as a human nasopharyngeal carcinogen. In the present study, 221 Wistar-Kyoto rats aged 21 days were randomly assigned to one of three experimental groups. Rats in group 1 (high dose group) were fed a powder diet of one part Chinese salted fish to three parts certified rat chow during the first 18 months. Similarly, rats in group 2 (low dose group) were fed a powder diet of one part salted fish to five parts rat chow for 18 months. Rats in group 3 were given rat chow only throughout the 3-year experiment. Four malignant tumours of the nasal cavity were observed among rats fed the experimental diets (three and one respectively in the high and low dose groups). No comparable tumours were observed in controls, compatible with the historical control rate of zero. Our results, therefore, further strengthen the hypothesis that Chinese salted fish is a human nasopharyngeal carcinogen; they also establish Wistar rats as a viable animal model for carcinogenicity studies of this food in the laboratory.