An epidemiologic study of Helicobacter pylori infection in three areas with high, moderate or low incidences of gastric carcinoma

Abstract

AIM: To study the relationship between the Helicobacter pylori (Hp) infection rate and the incidence and mortality of gastric cancer.

METHODS: The Hp infection rates of the natural population in three areas were detected by measuring the specific IgG antibody to Hp using the indirect ELISA method.

RESULTS: The Hp positive rates were 59.4%, 55.9% and 34.5% in the areas with high, moderate and low incidences of gastric carcinoma, respectively. The differences in incidence among the areas were significant (χ² = 25.029, P < 0.05). The Hp infection rate was the highest in the high incidence area of gastric cancer in people younger than 40 years. The Hp infection rate was 50% in children younger than 5 years in the high incidence area. The Hp infection rates were not different among the three areas in the people older than 40 years. The average levels of anti-Hp IgG in the high, moderate and low incidence areas were 2.3 ± 0.49, 2.04 ± 0.47 and 1.84 ± 0.46, respectively. Multivariate regression analysis showed that the Hp infection was related to bad hygienic habits, low income, frequent use of antibiotics, and mental depression. Univariate analysis showed that Hp infection might also be associated with raising animals in the home.

CONCLUSION: Gastric cancer is closely related to the incidence of Hp infection.

Key Words: Stomach neoplasms/etiology; Helicobacter infections/epidemiology

INTRODUCTION

Gastric carcinoma is the most common malignant tumor in China. However, the cause of the disease remains unclear. Many studies have proved that environmental factors may play a very important role in the pathogenesis of gastric cancer. Hp infection is an environmental risk factor for gastric carcinoma. In this study, we determined the Hp infection rates in areas with high, moderate or low incidences of gastric cancer using an indirect ELISA method. We then investigated the relationship of the Hp infection with the gastric cancer incidence.

MATERIALS AND METHODS

From December 1992 to February 1993, we collected samples from people in Changle County, a high incidence area of gastric cancer of Fujian Province, Huaiyuan County, a moderate incidence area of gastric cancer of Anhui Province, and Conghua County, a low incidence area of gastric cancer of Guangzhou City. A total of 639 subjects from 68 families in the high incidence area, 64 families in the moderate incidence area, and 63 families in the low incidence area participated. There were 358 males and 281 females, with ages ranging from 1 year old to 65 years old. Two milliliters of blood was drawn from each subject. Serum was separated and stored at -20 °C until the samples were processed for the anti-Hp IgG antibody by an indirect ELISA method. If the ratio of the OD of the subject to the OD of the Hp-negative control was ≥ 2.0, then the sample was considered Hp-positive. If the ratio of the OD of the subject to the OD of the Hp-negative control was < 2.0, then the sample was considered Hp-negative. The sensitivity of this method was 93.9%, and the specificity was 86.8%. Statistical analysis and multivariate regression analysis of all the data obtained were done with the SAS software on an AST-486 computer.

RESULTS

The overall positive rate of the anti-Hp IgG antibody was 50.5% (329/639) in these subjects. The Hp infection rates of the populations in the high, moderate and low incidence areas are shown in Table 1. The Hp infection rate in the high incidence area was higher than that in the moderate incidence area, and much higher than that in the low incidence area in people younger than 40 years. Also, the Hp infection rate in children under 5 years of age in the high incidence area was 50%, which was significantly higher than those in the other two areas (P < 0.05). However, the Hp infection rates were not different among the three areas in the subjects older than 40 years. The Anti-Hp IgG level in the subjects of the high incidence area was significantly higher than that of the other two areas (P < 0.01) (Table 2). A Mantel-Haenszel analysis showed that X1, X25, X29, X32, X39 and X51 were highly associated with an Hp infection (Table 3). Multivariate regression analysis and logistic regression analysis showed that X3, X11, X18, X25, X39 and X51 were risk factors for an Hp infection (Table 4).

Table 1 Helicobacter pylori infection rates of subjects from areas with low, moderate, and high incidence rates of gastric cancer.

Age (yr)	Low (Conghua County)		Moderate (Huaiyuan County)		High (Changle County)
	n	Positive rate (%)	n	Positive rate (%)	n	Positive rate (%)
1-4	13	15.4	14	35.7	14	50.0
5-9	43	30.2	17	41.2	42	54.8
10-19	32	37.5	23	43.5	32	53.1
20-29	27	33.3	66	63.6	44	72.7
30-39	30	33.3	34	64.7	40	67.5
40-49	23	43.5	28	53.6	19	47.4
50 +	29	41.4	31	58.7	38	55.3
Total	197	34.5	213	55.9a	229	59.4a

χ² = 25.029,

^aP < 0.05, compared with the area of low incidence rate (Conghua County)

Table 2 Anti-Helicobacter pylori IgG levels in subjects from areas with low, moderate, and high incidence rates of gastric cancer.

	n	(S/N)
Low (Conghua County)	197	1.84 ± 0.46b
Moderate (Huaiyuan County)	213	2.04 ± 0.47b
High (Changle County)	229	2.30 ± 0.49

^bP < 0.01, compared with the area of high incidence rate (Changle County)

Table 3 Multivariate regression analysis of Helicobacter pylori related variables.

N (Xi)	Variable	r	F	P value
X3	Drinking natural water	0.052	4.34	0.038
X11	Eating red pepper	0.079	8.57	0.003
X18	Poor dietary habits	-0.110	11.98	0.001
X25	Frequent use of antibiotics	-0.110	12.79	0.000
X39	Low income	0.087	21.14	0.000
X51	Mental depression	-0.108	4.23	0.040

Table 4 Univariate analysis of Helicobacter pylori related factors.

N (Xi)	Variable	x2M-H	P value
X11	Eating red pepper	10.53	0.001
X25	Frequent use of antibiotics	6.39	0.011
X29	Raising animals in the home	3.86	0.049
X32	Abdominal symptoms	5.82	0.016
X39	Low income	9.99	0.002
X51	Mental depression	5.26	0.022

DISCUSSION

Gastric cancer is the most common malignant tumor in China. The average yearly mortality from gastric cancer between 1975 and 1978 was 15.41 people out of 1000000 people. Interestingly, mortality rates varied by geographic location[1]. Changle County is located on the southeast coast and has the highest incidence and mortality rates from gastric carcinoma (120.47 people out of 1000000 people) in China. Conghua County of Guangzhou City has a low incidence rate of gastric carcinoma in China, with a mortality rate of one person out of 100000. Huaiyuan County of Anhui Province has a moderate incidence of gastric cancer. The mortality rate of gastric cancer approaches the average level in China[2-4].

In the present study, each family was taken as an observation unit for determining the Hp infection rates in Changle (high incidence), Huaiyuan (moderate incidence) and Conghua (low incidence) counties. The overall Hp infection rate was 50.55%. The Hp infection rate and anti-Hp IgG antibody levels in the subjects of the high incidence area were higher than those of the other two areas, especially in children younger than 5 years. However, the Hp infection rates were not different among the three areas in subjects older than 40 years.

Many studies have shown that atrophic gastritis incidence is associated with an Hp infection. The Hp infection rate was 60% to 90% in patients with atrophic gastritis and 92% in patients with active atrophic gastritis in China[5]. In other countries the Hp infection rate was 43.5% to 89.5% in patients with atrophic gastritis[6]. Atrophic gastritis is considered to be a risk factor for gastric cancer. The incidence of gastric cancer in high incidence areas is seven times higher than in low incidence areas of gastric cancer, and atrophic gastritis is usually more severe in high incidence areas of gastric cancer[7]. Notably, the majority of atrophic gastritis cases and Hp infections affect the gastric antrum. Anti-Hp IgG antibody levels were related to the number of Hp and the reaction of the gastric mucosa to Hp[8]. The Hp infection rates and anti-Hp IgG levels were higher, and the average age of the infected patients were younger in the high incidence areas of gastric cancer than in the low incidence areas[9,10]. This data suggests that gastric cancer might be associated with an Hp infection, and thus an Hp infection may be one of the risk factors for gastric cancer.

Multivariate regression analysis showed that drinking natural water, poor dietary habits, low income and mental depression were all risk factors for an Hp infection. Ling et al[8] proved that Hp can live in natural river water for approximately 10 days, indicating that Hp infection may be transmitted by water. Inhabitants of Changle County (high incidence area) usually drink natural water. The nitrate and nitrosamine levels are higher there than the nitrate and nitrosamine in water of other areas. Hp infection or long time exposure to high levels of nitrate and nitrosamine may destroy gastric mucosa and result in gastric cancer. It is hypothesized that an Hp infection and high levels of nitrate and nitrosamine in the drinking water may be the cause of the high incidence rate of gastric cancer in Changle County.

Graham et al[11] observed that the Hp infection rate was 70% in black people and 34% in white people in the United States. They also found that the Hp infection rate was higher in low-income families, which coincides with our results. Univariate analysis showed that an Hp infection was also associated with raising animals in the home. Some studies have shown that both humans and animals can be infected with Hp. Experimental Hp infection of the stomachs of newborn pigs, newborn dogs, and nude mice has been successful[12]. In addition, Euler isolated an Hp-like organism from the monkey, suggesting that humans and animals may transmit Hp to one another.

In summary, we observed an association between gastric cancer and Hp infections. Hp infection rates were higher and the age of the infected patents were younger in the high incidence area compared to the rates and ages in the low incidence area. The risk factors related to gastric cancer included low income, mental depression, and poor dietary habits. Our results also suggested that the gastric cancer incidence and mortality have positive correlations with Hp infection. In other words, Hp infection may be a risk factor for gastric cancer.