Study on environmental etiology of high incidence areas of liver cancer in China

Abstract

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

INTRODUCTION

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 EPIDEMIOLOGICAL CHARACTERISTICS OF LIVER CANCER

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 46.87/10^5[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 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 ECO-ENVIRONMENTAL GEOLOGICAL TYPES IN LIVER CANCER AREAS

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.

DRINKING WATER TYPES AND LIVER CANCER

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

RELATIONSHIP BETWEEN DRINKING WATER AND 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 type	Qidong in Jiangsu					Fusui in Guangxi
	Pond	Channel	River	Shallow well	Deep well	Pond	River	Deep well
Death rate	61.53	58.17	41.99	18.80	0.0	115.05	37.49	0.0
Number of samples	20	18	22	21	16	7	18	25
COD	4.66	3.85	3.55	3.20	1.28	48.27	0.75	0.197
Humic acid	0.43	0.36	0.28	0.18	0.08	0.58	0.18	0.042
NO3-	14.52	18.20	21.46	67.91	1.53	0.74	0.75	0.480
NO2-	0.54	0.48	0.38	0.28	0.04	0.061	0.008	0.0096

The death rate is 1/10⁵ and the unit of NO₃^-, NO₂^- is ppm.

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 PPM	Regression a	Coefficient b	Interrelation coefficient r
Humic acid	29.4985	78.6384	0.5981b
NO2-	53.1249	75.9767	0.4232a
COD	43.8098	0.4280	0.4881b
BOD	45.0576	0.6231	0.4872b
DO	191.8340	-19.0087	-0.7285b

^aP < 0.05,

^bP < 0.01, vs control.

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 .

THE RELATION BETWEEN NITROSAMINE AND 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 samples	Death rate of liver cancer 1/105	Dimethyl nitrosa mine ppb	Diethyl nitrosamine ppb
Sihe	74.96	3.8
Jiuchen	35.42	3.2
Yiliu	31.68	3.6
Mumin	80.80	2.4	2.2
Qutun	112.59	5.6
Zhongyuan	148.49	4.8	2.4
Lailu	95.36	4.2
Jiuta	18.38	0.8	0.4

MUTATION TEST OF DRINKING WATER

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 type	Cell micronuclei rate %	Cell chromosomal aberration rate %
Pond water 1	63.34	6.42
Pond water 2	59.66	4.76
Shallow well water 1	48.32	3.76
Shallow well water 2	42.66	3.21
Deep well water	3.30	0.75
Blank contrast	2.43	0.17

STUDY ON THE WATER QUALITY BEFORE AND AFTER THE CHANGE IN WATER SOURCE

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 acid	COD	DO	NH4
1	0.0224	0.53	44.24	6.10	0.34
2	0.0106	0.05	0.34	8.21	0.07

Note: 1. pond water, 2. deep well water.

Table 6 Contrast in water quality before and after the change in water.

Test item (ppb)	Se	Fe	Mn	Zn	nitrosamine
1	0.56	1110.88	198.33	9.29	4.20
2	0.39	164.60	10.14	50.47	0

Note: 1. pond water, 2. deep well water.

Table 7 Contrast in water quality before and after the change in water.

Test item	Plant cell micronuclei rate/%	HHPL
		micronuclei rate/%	chromosome aberration rate/%
1	10.34	59.61	4.76
2	5.96	3.30	0.75

Note: 1. pond water, 2. deep well water.

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.