Brief Reports Open Access
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2000; 6(4): 572-576
Published online Aug 15, 2000. doi: 10.3748/wjg.v6.i4.572
Study on environmental etiology of high incidence areas of liver cancer in China
Nian-Feng Lin, Jie Tang, Hoteyi S. Mohamed Ismael
Nian-Feng Lin, Jie Tang, College of Environment and Construction Engineering, Changchun University of Science and Technology, Changchun 130026, China
Hoteyi S. Mohamed Ismael, Baiqiuen Medical Science University, Changchun 130021, China
Nian-Feng Lin, male, born on 1932-12-31 in Wanhan City, Hubei Province, graduated from Baijing College of Geology in 1956, majoring in eco-environmental geology, having 52 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Prof Nian-Feng Lin, College of Environment and Construction Engineering, Changchun University of Science and Technology, Changchun 130026, China.
Telephone: +86-431-8502261
Received: February 1, 2000
Revised: February 23, 2000
Accepted: March 5, 2000
Published online: August 15, 2000

Key Words: liver neoplasms, etiology, epidemiology, water pollution, environmental carcinogens, nitrosamines, china, geology


China is a country with a high incidence of liver cancer in some areas[1]. Liver cancer has a wide distribution and threatens human health seriously. A ro ugh estimation shows that out of a population of 1.2 × 108 in liver cancer areas patients are more than 1.0 × 105. The environment of the liver cancer area is very complicated and has different characteristics in different regions. But the epidemic regularity of liver cancer is obvious, and the environment in the cancer areas has also distinct characteristics that contribute to the study on the environmental etiology of liver cancer[2-5].


The liver cancer discussed here has epidemiological characteristics like endemic , comparison and trend. The general investigation of liver cancer all over the country of China or local area shows that the high rate of liver cancer has been found in some provinces, counties, towns, and islands with the back-ground of the low death rate (10/105)[1,6]. The main areas of high rate of liver cancer chiefly concentrate in the coastal areas such as Jiangsu, Guangxi, Fujian, Zhejiang, Guangdong Provinces, and Shanghai City[7,8] (see Figure 1). Qi dong in Jiangsu Province and Fusui in Guangxi Province are two counties of the highest death rate of liver cancer in China and the death rates are 47.76/105 and 46.87/105[1,9]. As far as macroscopic environment is concerned, the risk area often has focused distribution and has a strict and steady dividing l ine between light and non-liver cancer areas. The risk area has peculiar charac teristics regarding landmark, geology, hydrogeology, and geochemisty[9,10]. It is an important way to study the cause of high incidence of liver cancer from the angle of environmental etiology.

Figure 1
Figure 1 Sketch map of liver cancer in China.

The area of high incidence of liver cancer is adjacent to that of the low i ncidence area and the death rate has great disparity. For example, the death rate in Fus ui is 46.87/105 while that in Niming County is 7.47/105, and the death rate in Qidong is 47.76/105 while that of Rudong County adjacent to Qidong is 20.6 1/105. The death rate in Tongxiang Town in Qidong County is 50.67/105 while that in adjacent Xining Town is 17.28/105. All these show that the carcinogens are distinctly different in the two adjacent environments[9].

The three epidemic trends of liver cancer may be summarized as follows: the change in epidemic curve from low to high, parallel development or from high to low. The trend reflects the change in the intensity of carcinogenic factor with time, and the epidemic curve of many high incidence areas of liver cancer belongs to the first type. The curve rose in the 1970s, while it gently went down from the end of the 1980s to the beginning of the 1990s. We think that organic pollution of the drinking water may be the reason for the rising of the curve, while the downward trend of the curve may be the result of changed water.


The cancer of digestive system in China has wide distribution and threatens huma n health seriously and liver cancer is the most serious one of all[1,11]. Distinct environmental characteristics were discovered in the high incidence a reas of liver cancer according to a survey and analysis on a large scale. It ref lects comprehensively the climate, hydrology, landmark, geology, geochemistry, drinking water, the degree of pollution, economic condition, the food custom and so on. However, the organic and reduction environment and the drinking water polluted by organisms are the most obvious and common characteristics. The high inc idence areas are classified into five geo-environmental types[10,12-14].

⑴ The denuded mountain environmental type: it is mainly distributed at the jun ction of three provinces of Hebei, Henan, and Shanxi in south Taihang Mountain. Esophagus, liver and stomach cancer are the common cancers. The climate is dry and the rainfall is about 500 mm-600 mm. The slopes are bare and are made up of carbonate and clastic rock. The ground has sparse plantation and the surface water and groundwater are very scarce. The drinking water condition is poor, and only a few residents drink stream and spring water, while most have to drink pool a nd pond water polluted with organic waste.

⑵ The Karst mountain environmental type: it is mainly distributed in Fusui and Longan County in Guangxi Province, the main cancers are liver and stomach cancer. The rainfall is sufficient about 1100 mm-1300 mm. The carbonate rock layer distributes extensively in the cancer areas belonging to Karst geographical are a. Underground rivers are developed while surface water is very scarce. People h ere mainly drink the water from dirty ponds or wells besides the ponds.

⑶ The river network plain environmental type: it is mainly distributed in Jian hu and Huai’an in the north of Jiangsu Province, Yangzhong and Taixing in the middle and lower reaches of Yangzi River. Main cancers are of the esophagus and liver. The area belongs to the alluvial and lake plains of the lower reaches of Yangzi River, and most of the cancer areas are in the lake-marsh depression whi ch is rich in humus sludge, peat, and biological deposition and CH4 is easily found escaping from the earth’s surface. The surface water and groundwater is rich but the runflow is stagnated.

⑷ The delta type: it is distributed in Qidong, Haimen, Rudong, Chongming Island in Yangzi River Delta and Nanhui County belonging to Shanghai City, Shunde, Jiangmen, and Foshan in the Zhujiang delta. Liver and esophagus cancer are the main cancers. The climate is humid with plenty rainfall. Most of the areas are sea and land mutual depositions that are mainly made up of sand, humus, peat, a nd biological deposition. The surface water and groundwater flow is sluggish and is severely polluted by organisms.

⑸ Coastal plain and island type: stomach, liver, and esophagus cancer are the m ain diseases. The cancer areas of coastal plain type are mainly distributed in Changle and Putian in Fujian Province. Most of them are sea and land mutual depos itions of coastal plains that are made up of clay, soil, and biological depositi on. The groundwater and surface water are rich, but severely polluted by organis ms. Dongshan Island in Fujian and Nan’ao Island in Guangdong Province belong to the island type which is a rocky hill and is covered by thin Quaternary deposit ion, and fresh water is scarce.

The classification of eco-environmental geology has contributed towards a deep study and contrast between the macroscopic and microscopic characteristics in disease areas, and searching for questionable carcinogenic factors of environment, and giving comprehensive protective measures.


Comparing the high incidence areas of liver cancer in China, we discovered that there exists a common faction in cancer incidence in these areas although the natural environment is different. It is that the groundwater or surface water is rich in humuns, the water flow is stagnant and is in an organic and reduction environment consisting of pools, ponds, cellars, trenches, channels, and the ground water in the swampland. The people in non-cancerous areas mainly drink groundwa ter or surface water which is not polluted by organisms. The water flow is smooth an d is in an oxidation environment such as springs, rivers, and shallow or deep well water[9]. Taking Fusui and Qidong as examples, we have constructed a figure that reflects the relation between the type of drinking water source and the death rate due to liver cancer (Figure 2). The figure illustrates that the death rate due to drinking the pond and pool water is the highest and due to deep well water is lowest.

Figure 2
Figure 2 Relation between the types of drinking water source and the death rates from liver cancer.

After affirming a close relationship between drinking water type and liver cancer, we tested the inorganic and organic compositions of all kinds of drinking water. We did not find any peculiar contents regarding common and trace elements, but some cancer areas were low in minerals and Se in water[13-16]. Howe ver the organisms in water were different and the death rate due to liver cancer was found to have a very close relationship with drinking water type and the degree of water pollution (Table 1).

Table 1 The organic pollution indicators of drinking water and death rate from cancer.
The drinking water typeQidong in Jiangsu
Fusui in Guangxi
PondChannelRiverShallow wellDeep wellPondRiverDeep well
Death rate61.5358.1741.9918.800.0115.0537.490.0
Number of samples201822211671825
Humic acid0.430.360.

From Table 1, it can be observed that water pollution indicator such as nitrate, nitrite, COD, and humic acid have an obvious relation with the drinking water type and death rate from liver cancer increases with a rise in the above indicators. In order to study the relationship between death rate and water quality, 29 water samples that corresponded to death rate due to liver cancer were chosen. The death rate and COD, DO, BOD, NO2-, and humic acid were used to make a correlation analysis to study the relationship between the death rate and the five factors. The regression equation is y = a + bx, y stands for the death rate due to liver cancer, xstands for the five factors. The results of the analysis are listed in Table 2.

Table 2 The analysis between various drinking water factors and death rate due to liver cancer.
Content PPMRegression aCoefficient bInterrelation coefficient r
Humic acid29.498578.63840.5981b

The results shows that humic, COD and BOD have a very remarkable positive relation with the death rate (P < 0.01), NO2- has a significant positive correlation. While DO has a very marked negative correlation (P < 0.01). That is to say, the lower the DO is in the water, the higher is the death rate. Pond water is severely polluted by organisms and is in a strong reduction environment lacking of DO. We postulate that the five factors given above can be used as important signs to judge the water quality and the death rate due to liver cancer .


It has been affirmed that nitrosamine is carcinogenic. Nitrosamine contents were observed in water from high incidence areas of liver cancer in the 1970s and 1980s in China, but the test method used was not very sensitive for semi-quan tity[18].

We collected 24 water samples from cancer-prone villages and non-cancer-prone villages in Fushui County to quantify the contents of nitrosamin e compound in water. Nitrosamine was not found in sixteen water samples taken from river, stream, and deep well water except in 8 samples of pond water. Dimethy l nitrosamine was the main compound in the pond water samples, only three pond wa ter samples contained diethyl nitrosamine. The death rate seems to have positive relation with the contents of nitrosamine (Table 3).

Table 3 The content of nitrosamine in pond water and the death rate due to liver cancer in Fusui.
Location of samplesDeath rate of liver cancer 1/105Dimethyl nitrosa mine ppbDiethyl nitrosamine ppb

Professor De Long Su [1] holds that the high incidence of liver cancer h as relation with water polluted by micro organisms. He carried out an Ames test on the drinking water in Qidong disease area and got a positive result. Li Sheng Zhang[9] carried out a micronucleus test using Zilu Grass from America on pond water in Fusui disease area and extracted liquid from the pond mud. His res ults show that high pollution degree corresponds to high micronucleus rate of pl ant cell and high death rate due to liver cancer. He also found that the micronu clei in clean deep well water in Karst area and corresponding water are very low .

Following some studies[19-24], we decided to carry out an HHPL muta tion test on pond water, shallow well water, and deep well water. Distilled water was used as a blank contrast.

The first test was the cell micronuclei test and the results showed that HHPL micronuclei rate found in the water that has been poisoned had a dose-effect relationship with the density of the samples and the higher the density of samples content was, the higher the micronuclei rate was. The micronuclei rate had a marked difference (pond water > shallow well water > deep well water ≥ blank). On evaluation by t test, the micronuclei rates of poisoned pond water and shallow well water were significantly different (P < 0.001).

The second test used was the mutation test of cell chromosome malformation test. The results showed that the mutation rate of chromosome aberration of HHPL has dose-effect with the density of each polluted water sample. Rates of chromo som e aberration caused by polluted water are statistically significant and similar t o micronuclei test as evaluated by t test, P < 0.001 (Table 4). This can be an important test for studying environmental etiology of liver cancer.

Table 4 Result of cell mutation test and polluted water samples.
Water source typeCell micronuclei rate %Cell chromosomal aberration rate %
Pond water 163.346.42
Pond water 259.664.76
Shallow well water 148.323.76
Shallow well water 242.663.21
Deep well water3.300.75
Blank contrast2.430.17

It has been accepted that liver cancer has close relations with the polluted dri nking water. The changed water project has been made in many cancer prone areas since 1980’s, especially in Fusui County, the changed water project has been implemented on a large scale, and the present water source is from the limestone layer. The depth of well is about 100 m-200 m. Most cancer prone villages have used this supply of water with beneficial results. We chosed nine villages supplied with changed water and observed the change in the water quality and human hea lth before and after. Before the water was changed, the pond water was severely polluted, and the color of water was brown and grey green, the water smelled terrible, and residents had many unhealthy symptoms such as pale cheeks, fatigue, distension of abdomen, menoxenia and liver cancer. After the water was changed, the deep well water was clear and sweet, the symptoms noted above gradually disap peared, residents felt sound and the liver cancer death rate lowered. The result s of water quality before and after the water was changed and mutation test are listed in Tables 5, 6 and 7.

Table 5 Contrast in water quality before and after the change in water.
Test item (ppm)NO2-Humic acidCODDONH4
Table 6 Contrast in water quality before and after the change in water.
Test item (ppb)SeFeMnZnnitrosamine
Table 7 Contrast in water quality before and after the change in water.
Test itemPlant cell micronuclei rate/%HHPL
micronuclei rate/%chromosome aberration rate/%

From Tables 5, 6 and 7, it can be observed that the water quality of deep well is betterth an that of pond water. Thus using a change in water source and additional treat ments, an improvement in human health and prevention in the occurrence of liver cancer[25-32] may be observed.


Project supported by National Natural Science Foundation of China, No 48970193

Edited by Zhu QR proofread by Mittra S

1.  Lini NF. Medicine environment geochemistry. Changchun City: Ji Lin Science and Technology Publishing House. 1991;242-256.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Gu GW, Zhou HG, The new concept of the cause of liver canceri Shijie Huaren Xiaohua Zazhi. 1998;6:185.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Liu WW, The study on etiology of hepatocytic liver cancer Shijie Huaren Xiaohua Zazhi. 1999;7:93-95.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Wu Y, Liu E, Zhang BC. The analysis of family history in the pati ents of primary liver cancer in different areas. Shijie Huaren Xiaohua Zazhi. 1998;6:178.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Zhou HG, Gu GW, The study on molecular epidemiology of liver cancer Shijie Huaren Xiaohua Zazhi. 1998;6:432.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Chen WS, Qiu JW, Cai SS, Lin K, Yuan H, Guo LM, Lin GB, Wan XA,Epidemiologic survey of liver cancer in Jieyang City of Guangdong Province Shijie Huaren Xiaohua Zazhi. 1995;3:39-41.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Wang ZQ, He J, Chen W, Chen Y, Zhou TS, Lin YC. Relationship between different sources of drinking water, water quality improvement and gastric cancer mortality in Changle County-A retrospective-cohort study in high incidence area. World J Gastroenterol. 1998;4:45-47.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Cai Lin, Yu SZ, The study on molecular epidemiology in Changle Coun ty of Fujiang Provence Shijie Huaren Xiaohua Zazhi. 1999;7:652-655.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Tang J, Lin NF. Relationship between drinking water quality and high frequency of the liver cancer in Fusui County in Guangxi. Huanjing Kexue Xuebao. 1996;16:287-293.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Yang KY, Tu JT, Li HM, Wang YQ, Zhi SP, The relationship between the distribution of stomach cancer and Tertiary stratum Shijie Huaren Xiaohua Zazhi. 1996;4:695-697.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Chung S. Chinese diet in the causation and prevention of cancer. World J Gastroenterol. 1998;4:36.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Wei XF, Cai YX. The dialectical diagnose of stomach cancer. Shijie Huaren Xiaohua Zazhi. 1993;1:31-32.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Ruan CC, Chen YH, Zhang ZQ. Drinking water and liver cancer. Shijie Huaren Xiaohua Zazhi. 1997;3:47.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Liu E, Zhang QN, Li WG. Effect of various drinking water on human micronucleus frequency in high risk population of PHC. World J Gastroenterol. 1998;4:183-184.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Worman HJ, Feng L, Mamiya N. Molecular biology and the diagnosis and treatment of liver diseases. World J Gastroenterol. 1998;4:185-191.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Wang GT, Tang ZY, Wu Z, Zhu FL. The study on the relationship between 141 patients of liver disease and trice elements. Shijie Huaren Xiaohua Zazhi. 1993;1:134-136.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Ci ZC. Liver disease and the metabolism of Ca and P. Shijie Huaren Xiaohua Zazhi. 1996;4:1-2.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Liu HQ, Ren CY, Jia LS, Yao XX, Ren XL. Effects of acute hepatic dam age on natriuresis and water excretion after acute normal saline loading in rats. Shijie Huaren Xiaohua Zazhi. 1996;4:176-178.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Cai JM, Zheng XL, Luo CJ, Gao JG, Cheng TM. The characteris-tics of D NA repair synthesis induced by DNA polymerase β in hepatoma cells after γ rays irradiation. Shijie Huaren Xiaohua Zazhi. 1997;5:705.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Xiao WH, Liu WW, Liu YY, Li Z. Control cancer gene p53 mutate of He patoma cells cancer. Shijie Huaren Xiaohua Zazhi. 1997;5:573.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Du QS, Fang DC, Luo YH, Lu Y, Liu WW. The study on N ras gene mutate in primary liver cancer. Shijie Huaren Xiaohua Zazhi. 1997;5:650.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Liu QF, Lou D, Shu JJ, Gove C, Williams R. The study on HBV-infect and Nras gene mutate of liver cancer in Guangxi Province. Shijie Huaren Xiaohua Zazhi. 1998;6:467.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Lee JH, Ku JL, Park YJ, Lee KU, Kim WH, Park JG. Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA. World J Gastroenterol. 1999;5:289-295.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Yakoob J, Hu GL, Fan XG, Zhang Z. Telomere, telomerase and digestive cancer. World J Gastroenterol. 1999;5:334-337.  [PubMed]  [DOI]  [Cited in This Article: ]
25.  Sun JJ, Zhou XD, Liu YK, Zhou G. Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model. World J Gastroenterol. 1998;4:314-316.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Yang BH. The current situation of early phase diagnose and treatment in liver cancer in China. Shijie Huaren Xiaohua Zazhi. 1993;1:133.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Wu MC. Clinical research advances in primary liver cancer. World J Gastroenterol. 1998;4:471-474.  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Li ZQ. Traditional Chinese medicine for primary liver cancer. World J Gastroenterol. 1998;4:360-364.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Tang ZY. Schmid advances in clinical research of hepatocellular carc inoma in China. World J Gastroenterol. 1998;4:4.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Tang CY, Clinical research advances in liver cancer, China Shijie Huaren Xiaohua Zazhi. 1998;6:1013.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  Gu GW, Zhou HG. Chinese medicine to prevent liver cancer. Shijie Huaren Xiaohua Zazhi. 1999;7:80-81.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Zou HG, Gu GW, Compound of vitamin to prevent liver cancer Shijie Huaren Xiaohua Zazhi. 1999;7:82-83.  [PubMed]  [DOI]  [Cited in This Article: ]