Between February 2003 and February 2013, the records of 2419 patients with histologically demonstrated gastric cancer were reviewed at four departments: the Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University; the Department of Digestive Medicine, Affiliated Hospital of Qinghai University; the Department of Medical Oncology, Affiliated Hospital of Qinghai University; and the Department of Digestive Medicine, People’s Hospital of Qinghai Province. The 10-year period was divided into two groups: previous 5-year group (Jan. 2003-Jan. 2008; n = 985) and past 5-year group (Feb. 2008-Feb. 2013; n = 1394). For each patient, the demographic information, clinical data and pathology reports were available in these Departments.

All the data could represent the epidemiology of gastric cancer in the Hehuang valley. Each patient provided informed consent, and the Ethics Committee of the People’s Hospital of Qinghai Province and Affiliated Hospital of Qinghai University approved the study protocol.

The inclusion criteria for the patients with gastric cancer were as follows: (1) primary gastric cancer confirmed by endoscopic biopsies or histological pathology after gastrectomy; (2) more than two generations dwelling in the Hehuang valley (including both of the Huangshui River basin and the Yellow River basin in the east of Qinghai province); and (3) gastric computed tomography (CT) scan with oral and IV contrast, detection of Helicobacter pylori (H. pylori), human epidermal growth factor receptor-2 (Her-2) expression, estrogen receptor (ER) and progesterone receptor (PR) in tumor tissue stained routinely by hematoxylin-eosin staining (HE) or by immunohistochemistry (IHC). The perineural infiltration, vessel invasion, lymph nodes metastasis, histological classification and grade should be confirmed by pathological examination. The exclusion criteria were: (1) dwelling outside of the Hehuang valley or less than two generations dwelling in the Hehuang Valley; and (2) missing clinicopathological data or deficient pathological information.

The stomach is anatomically divided into three portions; the upper (U), middle (M) and lower (L) portions. If more than one portion was involved, all involved portions were described as UML. All patients were subjected to gastric CT scan (PHILIPS Brilliance iCT; Enhanced scanning administration: Ultravist 300, 85 mL, 2.8 mL/s) with oral and IV contrast and barium-meal joint with gastroscope (OLYMPUSCV-260) examination in the upper gastrointestinal tract to locate the tumor. The in vivo endoscopic optical biopsy with paraffin sections observation was used for gastric cancer diagnoses. As proposed by the Japanese Society of Gastroenterological Endoscopy[14], the classification of early gastric cancer (EGC) was as follows: (1) type I: protruded type; (2) type IIa: superficial elevated type; type IIb: flat type; type IIc: superficial depressed type; and (3) type III: excavated type. The macroscopic classification of advanced gastric carcinoma was classified according to Borrmann[15] as type I, type II, type III and type IV.

The classification of histological type was based on the predominant pattern of the tumor (common types and special types), according to criteria of the World Health Organization (WHO)[16]. The common types were classified as papillary adenocarcinoma, tubular adenocarcinoma (including well-differentiated types and moderately differentiated types), poorly differentiated adenocarcinoma (including undifferentiated carcinoma), signet-ring cell carcinoma and mucinous adenocarcinoma; the special types were classified as adenosquamous carcinoma, squamous cell carcinoma, carcinoid tumor and other tumors. Meanwhile, tumors were also classified as intestinal-type or diffuse-type, according to Lauren[10].

Moreover, gastric CT scan with oral and IV contrast detection of H. pylori, Her-2 expression, ER and PR in tumor tissue stained routinely by HE or IHC were performed. The perineural infiltration, vessel invasion, lymph nodes metastasis, histological classification and grade should be confirmed by pathological examination.

To reveal the influence of dietary habits on gastric cancer in the Hehuang valley, 2310 healthy residents were enrolled in this study as controls. The inclusion criteria for the normal controls were (1) more than two generations dwelling in the Hehuang valley (including both the Huangshui River basin and the Yellow River basin in Qinghai province); (2) no diagnosis or suspicion of gastrointestinal cancer; (3) no long-term exposure to carcinogens; and (4) no family history of neoplastic diseases.

The background data pertaining to patients were entered into an SPSS database. SPSS 17.0 was used for the statistical analysis. χ² tests and Mann-Whitney U tests were run to assess categorical covariates and continuous variables, respectively. We set the significance level P≤ 0.05.

A total of 785 male and 200 female patients were involved in the previous 5 years group; there were 190 patients distributed in the age range of 18-44 years, while 795 patients were in the age range of 45-85 years. Of 1394 patients (1083 male and 311 female) in past 5 years group, 390 patients were distributed in the age range of 18-44 years, while 1004 patients were in the age range of 45-85 years. The detail demographic information, including nationality and family history, are listed in Table 1.

All patients were subjected to a barium-meal examination in the upper gastrointestinal tract to locate the tumor. The locations of the primary tumor in the previous (33.5%, in composition ratio) and past 5 years groups (27.0%) were both concentrated in the lower third portion of the stomach (Table 2). The result of Lauren classification in both previous (63.8%) and past 5 years groups (69.2%) indicated that intestinal was the major type of gastric cancer in the Hehuang valley. The proportion of early gastric cancer was significantly lower (in composition ratio) than that of advanced gastric cancer. Adenocarcinoma was the leading histological type of gastric cancer in the previous and past 5 years groups. The majority of histological type was moderate carcinoma (65.1% in the previous 5 years group and 73.9% in past 5 years group); compared with the previous 5 years group, the number of patients with moderate carcinoma had decreased in the past 5 years group.

Nearly half of the patients in the previous 5 years group had perineural invasion (49.1%) or vascular invasion (48.1%); however, there was a downward trend in the past 5 years group (39.5% and 38.5%). A low level of Her-2 expression was detected in both previous (7.5%) and past 5 years groups (6.3%). Moreover, compared with the previous 5 years group, there were a downward trend in H. pylori infection (43.8% vs 36.2%), ER expression (26.2% vs 4.6%), PR expression (24.4% vs 4%) and lymph node metastasis (90% vs 86.3%) in the past 5 years group. It was worth mentioning that huge downward trends existed for ER and PR expression. The detail characteristics of each element are listed in Table 2.

The patients in the 45-85 years age had a higher incidence of gastric cancer than those in 18-44 years age either in the past 5 years group (86.1% of Muslims, 83.3% of Tibetan and 84% of Han) or in the previous 5 years group (87.2% of Muslims, 83.3% of Tibetan and 83.9% of Han). The age distribution for most of the patients in the elderly group was between 60.55-65.50 years (data not shown), so the 60.55-65.50 years was the highest incidence age range for gastric cancer in Hehuang valley. The proportion of males among the gastric cancer patients was higher than that of females in the past 5 years group (81.4% of Muslims, 75% in Tibetan and 84% in Han) and the previous 5 years group (84.2% of Muslims, 88.9% in Tibetan and 80.8% in Han). There was no significant difference in the distribution of age (P = 0.511) and sex (P = 0.281) among the three ethnic groups in the Hehuang valley. The majority of Tibetan patients were positive for H. pylori infection (79.2% in male and 66.7% in female). The result of Lauren classification indicated that intestinal was the most common type of gastric cancer in the Hehuang valley. The majority of tumors in patients were located in the lower part of stomach, either in the past 5 years group or in the previous 5 years group. The detail characteristics of each element are listed in Table 3.

The proportion of the majority histological type of gastric cancer (moderately differentiated type) in the youth group (74.7%) was higher than that in the elder group (66.8%); the incidence risk in males and females were similar (69% vs 67.7%). By contrast, the proportion of the majority pathological type of gastric cancer (adenocarcinoma) in the youth group (89.7%) was less than that in the elder group (95.4%); the incidence risks in males and females were 93.5% and 95.9%, respectively. In total, 16.4% of patients in the youth group showed Her-2 expression-positive status. However, the proportion of patients with Her-2 expression-positive status in the elder group was only 3.9%. Meanwhile, more females showed Her-2 expression than males (19.2% vs 3.6%). Compared with the youth group, the majority of patients in the elder group were distributed in type I, type II and type III of the advanced stage. However, the majority of patients in the youth group were distributed in type III and type IV (Table 4). The numbers in the youth group with H. pylori infection-positive status (67.2%) were higher than in the elder group (32.1%). There was no significant difference in the proportion of sex in H. pylori infection (40.5% vs 41.4%).

To reveal the influence of dietary habits on gastric cancer in the Hehuang valley, 2310 healthy residents were enrolled in this study (Table 5). We conducted a survey for 10 dietary habits including smoking, drinking alcohol, rapid eating, irregular dinner-time, consumption of overnight food/preserved food/fried or grilled food/high-salt, high-fat and spicy food, drinking strong Boiled brick-tea and eating too hot or too cold food. The result showed that dietary habits such as smoking (P = 0.425), drinking alcohol (P = 0.963), irregular dinner-time (P = 0.600) and consumption of overnight food (P = 0.700) or preserved food (P = 0.750) had little effect on the incidence of gastric cancer in males and females. Compared with the healthy male residents, there were significant impact of rapid eating (P < 0.001) and eating too hot or too cold food (P < 0.001) on gastric cancer. Moreover, regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females.

A United States report showed that there has been a parallel five- or six-fold rise in adenocarcinoma[17]. A rising incidence of adenocarcinoma has also been reported from Canada[18], the United Kingdom[19], Australia[20] and the Netherlands[21]. Pohl et al[22] asked whether we are reaching a peak of adenocarcinoma incidence? The results of our study in the Hehuang valley would suggest that we are. Compared with the previous 5 years, the proportion of patients with adenocarcinoma had decreased (95.8%-91.6%), even though adenocarcinoma was still the leading histological type of gastric cancer (Table 2). Moreover, there was a more equal male-to-female ratio in adenocarcinoma (Table 4). In the year 1965, Lauren[10] indicated that the intestinal type is more common in males and older age groups. In the present study, the majority of gastric cancer in the elderly was intestinal (Table 4), which agreed with Lauren.

We observed a tendency for the location of the primary tumor to move up in the stomach, even if the lower 1/3 of the stomach was still the most common site of gastric cancer in the Hehuang valley. The proportion of upper 1/3 gastric cancer is increasing, and the proportion of squamous carcinoma/adenosquamous carcinoma has undergone a sharp increase. This was also accordance with the situation in Europe[23]. In Europe, Barrett’s esophagus is associated with this disease. Whereas in the Hehuang valley, the increase of upper 1/3 gastric cancer might be related to chronic gastritis, habits of food-intake and the high level of H. pylori infection.

Lymph node metastasis is the main way for solid tumors to metastasize; it is an essential factor for clinical, pathological staging and prognosis of cancer[24]. Tumor metastasis is a sign of deterioration. In this study, 90% patients in previous 5 years group showed lymph node metastasis (Table 2). The ratio was still very high in the past 5 years group. This indicated that the treatment of gastric cancer in the Hehuang valley would be more difficult. Meanwhile, the statuses of other factors such as Her-2, ER and PR were mostly negative. In 1994, the International Agency for Research on Cancer classified H. pylori as carcinogenic to humans[25]. Countries with high gastric cancer rates typically have a high prevalence of H. pylori infection[26]. Compared with the previous 5 years group, the proportion of gastric cancer patients with H. pylori infection had decreased in the past 5 years group (Table 2). Webb and Forman[27] indicated that H. pylori infection might disappear with the development of atrophic gastritis, which is present in many gastric cancer patients. This might explain the reason why there was a decrease in H. pylori infection in the Hehuang valley.

A previous study indicated that the incidence of gastric cancer rises progressively with age, meanwhile cases in patients younger than 30 years are very rare[28]. The number of gastric cancer patients in the elder group (48-85 years old) in our study was three times that in the youth (18-45 years old) group (Table 4), which correlates with the results of the previous study. However, near 25% of patients were distributed in the youth group in our study. A study with a large-size sample in South Korea[29] has evaluated the epidemiological features of young age gastric cancer. Therefore, the younger trend of gastric cancer may be happening not only in the Hehuang valley of China, but also worldwide. This should be a cause for concern.

Gastric cancer has a higher male-to-female ratio: reaching nearly 6:1 in the United States[30]. The high ratio also existed in the Hehuang valley: the 10 years observation of gastric cancer showed that the male-to-female ratio was 3.6:1 (Table 4). The moderately differentiated type was the major histological type of gastric cancer in male patients.

In England, the incidence of gastric cancer is related to ethnic groups[31]. There are significant variations in the overall incidence of gastric cancer between different ethnic groups living in the same region. The ethnic distribution of gastric cancer is different, with a preponderance in Whites over Blacks in the United States and non-Maoris over Maoris in New Zealand[30]. In the present study, the race with highest incidence of gastric cancer was Muslim, followed by Han (Table 3). However, there was no significant difference in the distribution of age (P = 0.511) and sex (P = 0.281) among three ethnic groups in the Hehuang valley.

Diet has a great influence on the human body. Continuous use of high doses of salt result in early atrophic gastritis and increase the later risk of stomach cancer[32]. Recently, a meta-analysis of prospective studies of habitual salt intake and risk of gastric cancer showed that dietary salt intake was directly associated with risk of gastric cancer[33]. In our study, there was a significant relationship (P < 0.001) between consumption of high-salt and gastric cancer in males and females (Table 5). Not only high-salt intake, but also high-fat and spicy foods were related to the incidence of gastric cancer. Unfortunately, quantitative data are lacking in our research. Tea is a specialty drink of China. Some studies have shown that tea consumption reduces the risk of gastric cancer[34,35]; however, others s disagree[36,37]. Boiled brick-tea, a popular fermented Chinese dark tea, is a common drink in the Hehuang valley. Our study showed that drinking strong Boiled brick-tea was significantly (P < 0.01) associated with gastric cancer (Table 5). Fungal growth during the production process is the key step[38], so the factor associated with cancer might be the Fungi. The relationship between tea consumption and cancer still needs further investigation. Moreover, some incorrect diet patterns, like eating too hot or too cold food and rapid eating in males, also lead to an increased incidence of gastric cancer (Table 5). These incorrect eating habits might related to the work pressure and male-dominated responsibility for their families. Therefore, advocating a scientific and reasonable diet would be very useful to reduce the incidence of gastric cancer. There were some limitations in this study, such as no investigation of the mortality rate and socioeconomic status of patients with gastric cancer. Thus, a further study on gastric cancer is necessary.

In conclusion, gastric cancers exhibit unique epidemiological features, characterized by marked dietary habits and differences based on race, sex, and age. The results in this study will help our understanding of the characteristics and trends of the clinical epidemiological data in the Hehuang valley, and provide a reference for the diagnosis and prevention of regional gastric cancer.

Gastric cancer is the second most common cause of death in all types of malignant tumors according to data released by the Ministry of Health. The incidence and mortality of gastric cancer vary geographically, with the highest rates in China, although a trend of declining incidence has been observed. Numerous epidemiological studies have been conducted in China to identify environmental lifestyle factors that contribute to the development of gastric cancer. Hehuang valley, one of the high-risk area of gastric cancer in China, is an important population center on the ancient Silk Road, and a systematic clinical epidemiological of gastric cancer is necessary. In this study, a clinical epidemiological study of gastric cancer in Hehuang valley was performed.

Hehuang valley, one of the most important stations on the Tang-Tibet Road and the ancient Silk Road, is located in the northeast of the Qinghai-Tibetan Plateau. The Hehuang valley has convenient transportation and relatively low elevation, and three-quarters of the population of Qinghai province are concentrated in this area. The authors investigated the clinical epidemiology of gastric cancer in Hehuang valley of China, and provided a reference for treatment and prevention of regional gastric cancer.

Differences were existed in races, sex, and age of patients according to the epidemiology of gastric cancer in Hehuang valley. Moreover, dietary habit was also an important factors contributing to gastric cancer.

Gastric cancers exhibit unique epidemiological features, characterized by marked dietary habits and differences based on race, sex, and age. The results in this study help to understand the characteristics and trends of the clinical epidemiological data in the Hehuang valley, and provide a reference for diagnosis and prevention of regional gastric cancer.

Hehuang valley is a fertile triangle zone carved out by the Yellow River and Huangshui River, and it is located between the Daban and Jishi Mountains, in the northeast of the Qinghai-Tibetan Plateau. Hehuang valley is also the transitional zone of the Qinghai-Tibetan Plateau and the Huangtu Plateau in the northwest of China where it is the main agricultural region. Furthermore, it includes thirteen administrative counties along the Yellow River and the Huangshui River in Qinghai province. It has a typical plateau climate, such as low pressure, hypoxia and cold in Hehuang valley through the year and its average height above sea level is 2000-3000 m. Native people dwelling in Hehuang valley comprise Hui, Salar, Tu, Tibetan and Han nationalities. Certain studies have shown that the regions along the Silk Road are high-risk areas of gastric cancer, and the Hehuang valley is one of the most important stations on the Tang-Tibetan Road and the ancient Silk Road.

In this study, the authors conducted a clinical-epidemiology study of gastric cancer in Hehuang valley of Qinghai Province in China. They included 2379 cases of gastric cancer from the past 10 years. They analyzed the following criteria: histopathological classification of gastric cancer, tumor location according to the anatomy of the stomach, age, sex, ethnic origin and dietary factors. The epidemiology of gastric cancer in Hehuang valley shows differences in its prevalence according to race, sex, and age of patients. Dietary habits were also important factors contributing to gastric cancer. The report represents a contribution to the study of the epidemiology of gastric cancer worldwide, especially in Asia.