Urban Rural Disparity in Westernization Related Cancers and the Increasing Incidence in Parallel with Socioeconomic Development and Urbanization from 2000-2015 among a Rural Chinese Population: An Observational Study

Abstract 
China used to have great urban rural disparity in socioeconomic development. Since the late 1980s, rapid socioeconomic development and urbanization have been taking place in rural settings. It is epidemiologically established that cancer scale and profile will transit as economy prospers and urbanization develops. However, there are few published studies reporting what changes are undergoing in cancer pattern in Chinese rural settings. Population-based tumor registration data collected by us in urban Shijiazhuang city (available for 2,374,827 people in 2012) and in rural Shexian County (available for 408,995 people since 2000) were used for urban rural comparison of age standardized incidence rate (ASIR) of westernization-related cancers in 2012, and the trend of biennial ASIR of these cancers for 2000-2015 in Shexian County was examined following a decade of rapid socioeconomic development and urbanization. From 1988-2015, the Gross Domestic Product per Capita (GDP) in rural Shexian County increased from 860 to 3000 US$, and urbanization rate from 22.4% to 54.8%. The biennial ASIRs of lung, colorectal, gallbladder cancer and leukemia in both sexes, and that of breast, ovary, thyroid, and kidney cancer in women increased significantly from 2000 - 2015. The increase from 2000-2001 to 2014-2015 in man and women for lung cancer was from 15.9 to 34.7 per 105 (P = 0.05) and 9.6 to 16.7 (P = 0.00), for colorectal cancer from 6.6 to 15.9 (P = 0.00) and 4.0 to 11.7 (P = 0.00), for gallbladder cancer from 0.1 to 2.4 (P = 0.00) and 0.3 to 2.7 (P = 0.00), for leukemia from 2.8 to 7.7 (P = 0.00) and 2.3 to 6.2 (P = 0.00); and in women for cancer of breast from 2.8 to 17.3 (P = 0.00), kidney from 0.2 to 2.4 (P = 0.00), ovary from 0.2 to 4.3 (P = 0.00), and thyroid from 0.2 to 4.2 (P = 0.00). Notwithstanding these increases, their ASIRs in 2012 in Shexian County were still significantly lower than that in Shijiazhuang city. Westernization-related cancer is increasing rapidly in rural China. Comprehensive measures are needed to strengthen prevention to ensure sustainable development.


Introduction
China has experienced rapid socioeconomic development and urbanization since the late 1980s. It is epidemiologically established that cancer scale and profile will transit as economy prospers and urbanization develops [1]. However, there are few published studies reporting what changes are undergoing in cancer pattern and how fast have the changes occurred in Chinese settings [2] [3] [4] [5] [6]. Using population-based tumor registration data, we previously reported a rapidly decreasing trend in the age standardized incidence rate (ASIR) of Helicobacter Pylori infection-related upper gastrointestinal cancer (UGIC) in parallel with socioeconomic development and urbanization from 2000-2015 in Shexian County, a rural area where endemic rates of upper gastrointestinal cancers were found in the past [7]. This time we studied the trend in the ASIR of westernization-related cancers in relation to socioeconomic development and urbanization. The ASIR of westernization-related cancers was also compared between Shexian County and a neighboring urban city (Shijiazhuang city) to examine the urban-rural disparity in relation to socioeconomic development status. Our aim is focused on prevention of westernization related cancers for sustainable development.

Materials and Methods
A cross sectional study is performed to assess urban-rural disparity in ASIR of westernization related cancers in 2012 between rural Shexian County and urban Shijiazhuang City. We chose 2012 for comparison because population-based tumor registration data (incidence data) in Shijiazhuang city is available only for 2012, but in Shexian County available since 2000. We then examined the increasing trend of biennial ASIR of westernization related cancers in Shexian County from 2000-2015 in parallel with progressive socioeconomic development and urbanization.

Background of Shexian County and Shijiazhuang City
Shexian County of Hebei province is an entirely mountainous land in the up-ranges of South Taihang mountain, ranging from 36˚17' to 36˚55' north latitude and adjoining the three provinces of Hebei, Henan, and Shanxi ( Figure 1). It is a northern neighbor of Linxian County of Henan province and a northwestern neighbor of Cixian County of Hebei province. All these counties are noted for extraordinary high incidence rates of esophagogastric cancers [8]. Shexian County consists of a county town and 580 villages, its' population was 408,995 in 2012. The economy of the county relies on grow of rice, wheat, persimmon, Chinese prickly ash, walnut, agricultural product refinery, food manufacture and tourist. A quarter of Shexian population, mainly young or middle-aged villagers, is floating between the village and the county town doing seasonal jobs. Its' domestic gross product per capita in 2012 was 2700 US$. The traditional diet in Shexian County consists of a self-made staple food of rice or steamed bun flavored by dishes of vegetables. Physical activities for villagers mean manual labor. But in the county town, people aged 60 or above do walking or jogging in the morning or evening (Table 1).  As of China, health care in Shexian had been hospital centered. From 1949 until 2010, only government or public employees had been protected by public medical insurance programs. For villagers, only basic medicine was provided free of charge by a rural corporative medical insurance program [9].
As the urban counterpart for comparison,Shijiazhuang is located 250 kilometer northeast of Shexian County, at the cross point of north-south bound Peking-Wuhan railway and the east-west bound Dezhou-Taiyuan railway, and at the foot of Taihang Mountain. The registered urban population in 2012 was 2,374,827.
Shijiazhuang has not been a city before 1953. It used to consist of several dozens of villages. Its urbanization began as late as 1953, when it was chosen by the Chinese central government as the capital city of Hebei Province and as one of cities with development priority during the first national five-year program (1953)(1954)(1955)(1956)(1957). During implementation of the program, the North China Pharmaceutical Corporation, which is the biggest anti-biotic factory in Asia, and five modern textile plants were established in Shijiazhuang city. In 60 years, its registered urban population increased from 182,188 in 1953 to 2,374,827 in 2012. In 2012, the Gross Domestic Product (GDP) per capita of Shijiazhuang city was 6964.8 US dollar, ranking 119 th among the 150 Chinese cities which had a GDP higher than the average of 6102 US $ for a total of 293 prefecture-level cities [10].

Statistical Methods
Gender and age specific cancer incidence rates were calculated, and the Segi standard world population (modified by Doll) was used to calculate ASIRs [11].

Collection of Socioeconomic Development and Urbanization Data
Data of socioeconomic development and urbanization in both Shexian County and Shijiazhuang city are collected by visiting local government department and their websites. Prevalence of local risk factors for westernization related cancers were obtained from published data. The study was approved by the Institutional Ethics Review Board of 4 th Hospital of Hebei Medical University.

Urban Rural Disparity in Socioeconomic Development
Though both starting from a similar rural agrarian background 60 year ago, Shexian is considerably under developed than Shijiazhuang. In 2012 the GDP per capita were 6964.8 vs. 2700 US$. The yearly disposable income per capita was 1538 vs. 750 US$. Shijiazhuang people spent 40% of their disposable income on food while the percentage among Shexian people was less than 20%. The percentage of animal food in Shijiazhuang and Shexian was 30% and 19% respectively. Shexian people are physically more active for working or walking than Shijiazhuang people, and the percent of obesity is significantly ower. Regarding smoking prevalence, proportion of daily smoker among men in Shexian County in 2010 was significantly higher than in Shijiazhuang city (40% vs 35%, P = 0.01), but among women it was identical. In association with significant urban rural disparity in socioeconomic development, the life expectancy was 4-year longer in Shijiazhuang than in Shexian in 2012 [14]- [20] (Table 1).

Socioeconomic Development and Urbanization and the Changing Risk of Non-Communicable Diseases since the Late 1980s in Shexian County
Shexian has been a traditional rural agrarian county, but as is the case of most D. G. Wen et al. . Every day, buses run between the county town and villages, picking up villagers to and from working/shopping. In the past, walking is the principle means of transportation in this mountainous area, but now with greatly improved road condition, more and more villagers are in possessing of cars and motor bikes.
Because of changed diet, reduced physical activity, and migrating from the rural to urban environment, lifestyle is getting more and more westernized. The prevalence of overweight (BMI ≥ 24 kg/m 2 ) among 18-69 years adults in Shexian County tripled from 1991 (11.0%) to 2010 (33.0%), and the prevalence of obesity (BMI ≥ 28 kg/m 2 ) among 18 -69 years adults reached 15% in 2010 [15] [16]. With female children, mean menarche age decreased from 13.8 years-old before 2000 to 12.4 years-old by 2015, as we surveyed retrospectively by a randomly chosen sample of high school girls at the beginning of 2000 and 2015 respectively. Regarding fertility rate, because one-child policy has been implemented from 1978 till 2013, the total fertility rate has remained stable at 1. 8

Trends of Westernization-Related Cancers from 2000-2015 in Shexian County in Parallel with Unsustainable Socioeconomic Development and Urbanization
In parallel with unsustainable socioeconomic development and urbanization, ASIR of westernization-related cancers increased significantly, including the cancer of lung, colorectal, gallbladder, and leukemia in both sexes and breast, ovary, thyroid, bone carcinoma, and kidney cancer in women (Table 3, Figure  3). Among men, the biennial ASR of lung cancer increased from 15.9 to 34.7 with an averaged biennial percent change (ABPC) of +2.8% (P < 0.05), colorectal  cancer increased from 6.6 to 15.9 with an ABPC of +6.0% (P = 0.00), gallbladder cancer increased from 0.1 to 2.4 with an ABPC of +28.7% (P = 0.00), and leukemia increased from 2.8 to 7.7 with a ABPC of +7.4% (P = 0.00); and among women, the biennial ASR of lung cancer increased from 9.6 to 16.7 with an ABPC of +3.4% (P = 0.00), colorectal cancer increased from 4.0 to 11.7 with a ABPC of +5.5% (P = 0.00), gallbladder cancer increased from 0.3 to 2.7 with an ABPC of +15.6% (P = 0.00), leukemia increased from 2.3 to 6.2 with an ABPC of +7.9% (P = 0.00), breast cancer increased from 2.8 to 17.3 with an ABPC of +10.2% (P = 0.00), kidney cancer increased from 0.2 to 2.4 with a ABPC of +16.2% (P = 0.00), ovary cancer increased from 0.2 to 4.3 with an ABPC of +12.4% (P = 0.00), and thyroid cancer increased from 0.2 to 4.2 with an ABPC of +23.4% (P = 0.00). Notwithstanding decades of increase in the incidence rate of westernization-related cancers, by 2012 the ASIRs of most these cancers in Shexian County were still significantly lower than that of the urban counterpart (Shijiazhuang city), such as female breast (14. (Figure 2), when the GDP per capita differed by US$ 2700 vs. US$ 6964 between the two places. These results suggest that the increasing with westernization related cancers will continue for many years in the future as economy prospers further in Shexian County.

Discussion
Socioeconomic development and urbanization is a double-edged sword to disease transition. Though in early stage it is most effective in tackling infection or under nutrition related diseases such as UGIC in under developed populations, the adversary aspects gradually emerge in the form of increasing incidence of non communicable diseases (NCDs), including life-style westernization related cancers [21]. In this study we found although Shijiazhuang and Shexian had for lung, colorectal, pancreas, gallbladder, kidney, leukemia, thyroid, brain, and multiple myeloma, and positive associations were also observed for testicular, bladder, lip/oral cavity, Hodgkin lymphoma, and melanoma of the skin in males, and breast, ovarian cancer, corpus uteri, and non-Hodgkin lymphoma in fe-

males. The similarity between what is observed globally and in Shexian County
suggests the effect of socioeconomic development on cancer transition is universal [22].
What is happening in Shexian County has policy implication for the whole country. Between 2010 and 2015, urbanization in China had been taking place at the rate of 3.1% annually [23]. It is expected that 1 billion people will live in Chinese cities by 2030 [24]. Chinese over the age of 65 now number 140 million, and the number is expected to grow to 230 million by 2030. High-risk behaviors like population ageing, smoking, sedentary lifestyles and obesity, as well as air pollution, take a huge toll on health. Non-communicable diseases account for more than 80 percent of 10.3 million deaths every year, and are responsible for 77 percent of the loss in healthy life. As a result, expenditures on health care have been increasing continuously in recent years. A greater challenge faced by China is that the high growth rates of health expenditure may be difficult to sus-tain under present economic slow-down [25]. Therefore we must swift to a road of environmental friendly and health development.
Fighting the obese epidemic is one of key campaigns to prevent westernization related cancers. As concluded by World Cancer Research Fund (WCRF)/ American Institute for Cancer Research (AICR) in 2007 in the second report on Food, Nutrition, Physical Activity and Prevention of Cancer, body fatness is a convincing cause of cancers of colon and rectum, breast, endometrial, esophagus (adenocarcinoma), pancreas, and kidney, and it is a probable cause of gallbladder cancer [26]. This WCRF/AICR conclusion was updated in 2016 on the bases of 1000 new studies and concluded further that absence of excess body fatness reduces the risk of another 8 cancers, including cancers of the gastric cardia, liver, gallbladder, pancreas, ovary, thyroid, meningioma, and multiple myeloma [27].
Control of overweigh and obese in rural China involves more than life style modification on the individual level. As we see in Shexian, in over a decade of market economy development and urbanization, the traditional home made whole grain, vegetable, low energy but high dietary fiber food gives way to a market supplied, high animal product, and energy rich diet. As a result, the rural urban migrating populations become obese before they get rich, and the burden of obesity has shifted markedly to marginal groups and children [28]. As pointed out by Wang and Zhai [28], a healthy food environment has to be developed in rural China. In seeking profit, food companies are not bothered to consider the healthfulness of their products. The public is not very clear about what constitutes health food, and laws regulating manufacture and marketing of food are missing. For example there are no policies regarding marketing of food via television, there are no requirement over package labeling of the many thousands of food found in supermarkets and convenience stores that dominate the Chinese food system, little has been done to control the rapid increase in consumption of fast food and sugary beverages among children, and fiscal taxation and price regulation to shift consumption toward healthier foods is nonexistent. To establish any of these, incorporated efforts by all society are needed, including political commitment, legislation, government regulation, taxation, and above all, health food education.
In addition to overweight and obesity, tobacco smoking, excessive alcohol drinking, outdoor air pollution are also declared as established risk factor of westernization-related cancers by WHO [29]. Because exposure to these risk factors is determined to an extent by social economic activities and unsustainable production and consumption, prevention also requires strong and active political interventions. For example, a reduction in smoking of about a third by 2025, as suggested by the 2013 World Health Assembly to prevent lung cancer in developing countries [30], could be achieved by tripling the specific excise tax on tobacco, because this could produce multi-sector effect [31]. In 2013, IARC declared outdoor air pollution as a first class carcinogen [32]. In September 2013, D. G. Wen et al. the Chinese State Council issued the Action Plan on Prevention and Control of Air Pollution with the goal of cutting PM2.5 (particulate matters with diameter less than 2.5 μm) concentrations by 15% -20% over three economic zones in 2017 compared with 2012, and PM2.5 and other air pollutants have been measured nationwide on hourly basis since January 2013 [33]. According to James Lents, a veteran US policymaker responsible for cleaning up pollution in Los Angeles decades ago, it took the US forty years to control air pollution [34]. In comparison, China has made swift progress by incorporated environment protection policies such as cutting coal use, reducing iron/steel production, removing old vehicles, etc [35]. According to Wang et al., the mean concentration of PM2.5 at 512 stations in China during the winter and spring of 2015 (e.g., from Dec. 2014 to Feb. 2015 and from Mar. 2015 to May 2015) decreased by 20% and 14% compared to the previous year, respectively [36].
Our study has some strength. Over a decade later after progressive socioeconomic development and urbanization in a formerly disadvantaged rural population, we noted an increasing trend of westernization-related cancers over a 16-year period. Our study reveals a realistic view regarding the effect of urbanization on cancer transition. Second, the incidence rates of cancer were obtained through population-based tumor registration by standard of International Association of Cancer Registry established by the International Agency of Cancer Research (IACR). Population-based screening programs have never been implemented for lung, female breast, and colorectal cancer in Shexian County. Therefore, the increasing trend in the incidence of urbanization related cancers should not have been influenced by screening.
A weak point of our study is only one year (2012) tumor registration data was available for urban Shijiazhuang city, this may limit the representativeness of our urban-rural comparison results. Secondly we choose only one County of Shexian to represent whole rural China. The representativeness of present study needs to be carefully considered. Our results need to be validated in other populations.

Conclusion
In summary, we note a clear rural-urban transition of cancer pattern along with rapid social economic development and urbanization in a rural Chinese population. We believe diet transition, increasing body fatness, and environment deterioration are responsible. To avoid the tragedy already caused by westernization cancers to many industrialized countries, we recommend that comprehensive actions including policy making, legislation, and taxation be taken by government and whole society to fight the epidemics of obesity, tobacco smoking, and air pollution, to ensure health and sustainable development.

Funding
This work is supported by the Key Medical Research Subjects in Hebei Province [2012] No 2056 headed by Prof Shan Baoen (baoenshan136@163.com).