Gastric Cancer Mortality Trends in China (2006-2013) Reveal Increasing Mortality in Young Subjects

Discussion

Many changes in society can be expected to impact on GC-related death, especially increased screening but also the rapid development many societies undergo. At present, there exist little data reported as to how all these developments have affected GC-associated mortality. The present study documents these changes and reveals a relative increase of GC-related death in younger subjects. Thus, our data calls for programs aimed at reducing GC in this population specifically.

This study involved a secondary analysis on the basis of DSPs published over the years. There are unfortunately limitations in the comprehensiveness and timeliness of information. For instance, we can only superficially analyze the conditions on the national death of GC, the incidence rate, the course of the disease, other information on GC, as well as the latest data for 2014 and 2015, which are still lacking. In addition, since the result of the data set is the summary of the death case submitted by each surveillance point, the phenomenon of report omission is inevitable, indicating that our research data are underestimated. However, the DSPs system is currently the most representative and authoritative continuous data system on the cause of death in China. This published data set can reflect the variation trend on the death of various diseases and present the characteristics of the death of different genders, ages and territories. Thus, we feel the trends observed as credible.

According to a Chinese cancer registration report, the incidence of GC in China increased by 12% (from 32.23/100,000 in 2005 to 36.21/100,000 in 2009) (1, 20). In this study, we analyzed GC death data from 2006 to 2013 and our results indicate that crude mortality rate slightly increased in seven years by 8.2%. However, age-standardized mortality revealed a descending trend, which decreased by 17.8% (from 21.78/100,000 to 17.98/100,000). Divergent trends between crude and age-standardized mortality are exactly a representation of an aging population structure under today's rapid developing conditions. Compared to the increasing incidence of GC, the decline in standardized mortality rate is also related to the improvement in medical healthcare. In addition, the development of diagnostic techniques and enhancement of health consciousness have obviously increased the early diagnostic rate of GC. For instance, in Feicheng, Shandong province, China, endoscopy screening test for GC has been listed as an effective method for people older than 40 years (21). Meanwhile, improvement in operation skills, standardization of GC D2 surgery and development of tumor chemotherapy have also played a vital role in decreasing GC mortality (22).

Our study found that the standardized mortality of GC in males (25.66/100,000 to 33.89/100,000) was higher than in females (10.72/100,000 to 14.79/100,000) with a sex ratio of 2.0 to 2.5. In particular, people over the age of 40 have an even higher male predominance in mortality, which is consistent with other previous global reports and studies (23). This phenomenon may be due to the different social roles between males and females in which men usually have higher working pressures, irregular diet, more frequent social activities and other lifestyle problems, such as drinking and smoking (24). An epidemiological set of data in Korea included a total of 3,242 patients with GC between the age of 18 to 45, with all subjects being stratified into three groups based on age (A: 18-30 years; B: 31-40 years; C: 41-45 years). Male-to-female incidence ratio was 1.2:1.0 and male-to-female incidence ratios, based on age groups, was 1.0:1.6 in group A, 1.0:1.0 in group B and 1.7:1.0 in group C, respectively. This indicates the higher incidence of GC in females at younger ages (24). This is consistent with our study in which a higher mortality of GC in females was observed in the 20- to 24-year-old group. This might be related to the critical role of sex hormones, especially the different estrogen levels in young females, in the pathogenesis of gastric cancer (24, 25). Kim et al. found that females with GC were significantly younger and had a different signet ring cell (SRC) histology compared to males; furthermore, females had significantly poorer prognostic factors among young patients (aged ≤45) with SRC (26). Chung et al. further confirmed that excessive exposure to estrogen with a lack of progesterone is a key factor for the development of GS in young females (24).

In our study, we found that both urban and rural standardized mortality decreased by 12.8% and 20.8%, respectively. The standardized mortality of GC in rural areas (19.17/100,000-26.46/100,000) was higher compared to urban areas and the urban-rural proportion fluctuated from 0.6 to 0.9. In age-defined subgroups, we found that there was no statistical difference in mortality in both the 0- to 35- and 40- to 44-year-old groups between the urban and rural areas (p>0.05), while all other age groups demonstrated a higher mortality rate in rural areas than in urban areas. Guo et al. used join point analysis to detect changes in trends and generalized additive models to study birth cohort effect of risk factors between 1987 and 2009. They also found that both urban and rural age-standardized mortality decreased at different time intervals from 1987 to 2009 and in rural areas was higher compared to urban areas in both male and female; however, their study was conducted for all ages and failed to compare data between age groups (27).

This geographically-related difference was also present in correlation to studies conducted in Lithuania, Korea and Brazil (28-30). This rural-urban gap can be mainly explained by different healthcare recourses and prevention methods. H. pylori infection has been identified as the most important risk factor for gastric cancer, which was widely distributed in populations of developing countries, such as Brazil and China (27, 31, 32). In these countries, rural and urban areas are not strictly comparable due to lower economical levels, insufficient healthcare resources, poor living conditions and unhealthy eating habits in rural areas, which are directly related to the higher prevalence of Helicobacter pylori infection (33).

Mortality in Eastern and Middle areas was significantly higher than in Western areas, especially in individuals older than 65 years (p=0.0000). First, this may be due to higher economic levels with seriously aging populations in the Middle and Eastern regions. Secondly, possible dietary factors, such as the salty food, and low consumption of vegetables and fruits have been related to GC development (34, 35). As the majority of the Eastern regions are coastal cities, the corresponding intake of sea products is higher, causing higher intake of salts. A recent meta-analysis indicated that medium or higher intake of salt could increase the incidence of GC, when compared to a lower salt intake with risk ratio (RR) values of 1.68% (95% confidence interval (CI)=1.17-2.41) and 1.41% (95% CI=1.03-1.93), respectively (36). In addition, obesity was also related to an increased risk of early GC (both with respect to cardia and non-cardia cancers). In a recent nationwide case-control study (37), over one-third of Chinese adults were overweight or obese, while in Eastern and Middle major cities like Beijing and Shanghai more than half were overweight or obese (38). As Huang et al. confirmed that an increased body mass index (BMI) was associated with an increased risk of gastric high-grade dysplasia in both men and women and higher serum total cholesterol increased the risk of gastric non-cardiac high-grade dysplasia in women (39), obesity seems important factor explaining GC mortality trends.

Our study revealed an increasing trend of mortality in young patients. From 2006 to 2013, both crude and standardized mortality rates in the 0- to 29-year-old group increased by 22.3% and 16.2%, respectively. Furthermore, the composition of GC-caused death in all malignant tumor-related deaths also increased from 3.20% in 2006 to 3.87% in 2013. Merchant et al. evaluated the trends of gastric cancer incidence rates from 1992 to 2011 by using the Surveillance, Epidemiology and End Results (SEER) registry by calculating the annual percent change (APC) across three age groups (20-49 years, 50-64 years and 65 years or older) and four racial/ethnic groups (Hispanics, non-Hispanic whites, blacks and Asian/Pacific Islanders), they found the APC of the incidence of gastric cancer in young Hispanic men (20-49 years) places it among the top cancers with rising incidence in the USA (40). Several studies have reported more advanced tumors' presentation in young populations. Rona et al. (41) demonstrated that patients with GC in the younger group (YG) (aged ≤45 years) had a higher incidence of stage III/IV disease (86.8% vs. 57.9%, p<0.001), poorly-differentiated carcinoma (95.9% vs. 74.4%, p<0.001) and signet-cell type tumor (88.4% vs. 32.2%, p<0.001) relative to the older group (OG). Furthermore, obesity has been associated with GC (37, 42), with obesity rates rising in the young (43). Wang et al. analyzed data collected from children 7-17 years old from the China Health and Nutrition Survey (CHNS) conducted in 1997, 2000, 2004, 2006, 2009 and 2011. From 2,814 participants with 6,799 observations, the prevalence of overweight and obesity increased in boys and girls between 1997-2011 from 6.5% to 15.5% in boys and from 4.6% to 10.4% in girls (44). It is, thus, tempting to link the specific increase in GC-related death in the young to increases in obesity in this group; obviously, however, further work is necessary to confirm this notion.

Therefore, more studies on GC incidence in young patients needs to be conducted, in order to validate the appropriate age for screening tests in high-risk populations, especially in individuals under the age of 30. Direct measures and strategies aimed at risk factors and treatment improvement should be proposed to inhibit the growth trend of GC in young people.