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Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control.
Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of the 29 cancer groups were calculated based on sex, age, region, and country. In addition, separate analyses were performed for major cancer types.
In 2019, more than 10 million people died from cancer, which was approximately twice the number in 1990. Tracheal, bronchus, and lung (TBL) cancers collectively showed the highest death rate, and the ASDR of pancreatic cancer increased by 24%, which was cancer with the highest case fatality rate (CFR). The global cancer ASIR showed an increasing trend, with testicular cancer, thyroid cancer, and malignant skin melanoma showing a significant increase. The ASDR and ASIR of cancer in males were about 1.5 times higher than that in females. Individuals over 50 years had the highest risk of developing cancer, with incidences and deaths in this age group accounting for more than 85% of cancers in all age groups. Asia has the heaviest cancer burden due to its high population density, with esophageal cancer in this region accounting for 53% of the total fatalities related to this type of cancer in the world. In addition, the mortality and morbidity of most cancers increased with the increase in the development or socio-demographic index (SDI) in the SDI regions based on the World Bank's Human Development Index (HDI), with cancer characteristics varying in the different countries globally.
According to the World Health Organization (WHO) statistics, in 2019, cancer ranks as the first or second leading cause of death in 112 countries globally and third or fourth in another 23 countries . In countries with higher economic development levels, mortality from stroke and coronary heart disease are decreasing, while cancer is becoming the main and only disease hindering life expectancy . Due to population growth and aging, a significant downward trend of the main high-risk cancers has not been seen yet, and their burden has increased rapidly in some countries. This reflects the changes in the prevalence and distribution of main risk factors related to social and economic development [3, 4].
The types of cancer were assigned into 29 cancer groups according to the International Classification of Diseases (ICD). The annual incidence, death number, and age-standardized rate of the 29 cancer types in different genders, regions, countries, and ages were collected from the GBD database. Data from 204 countries were collected. Further, these countries were divided into five regions (low, low-medium, medium, high-medium, and high level) based on the socio-demographic index (SDI). In addition, the global social-economic development levels were divided into four levels: high, upper-middle, lower-middle, and low level based on the HDI. Based on geography, the world was divided into 21 regions (Table 1). Morbidity and mortality in these regions were calculated to unearth the trends in the epidemiology of malignant tumors in the regional environment, national ethnicity, and living habits. The cancer incidence, mortality, and morbidity were determined using estimates from individual cancer registries or aggregated databases, including the Cancer Incidence in Five Continents (CI5), EUREG, and NORDCAN. Since most cancer registries only had reports on cancer incidence and where data on mortality for some locations and time points were scarce, mortality was estimated from the cancer incidence using separately modeled mortality-to-incidence ratios (MIR). The uncertainty interval (UI) was set at 95%. The GBD estimates calculations were made 1,000 times to determine the UI, using distribution samples rather than point estimates for data inputs, data transformations, and model choice. The 95th uncertainty interval was determined by the 25th and 975th value of the 1,000 values after ordering them from smallest to largest. Larger uncertainty intervals result from limited data availability, small studies, and conflicting data, while smaller uncertainty intervals result from extensive data availability, large studies, and consistent data across sources. Additional metadata from each source are available in the online GBD citation tool, -2019 [6,7,8].
We used age-standardized incidence rates (ASIR) and age-standardized death rates (ASDR) to quantify regional morbidity and mortality trends in the 29 cancer types. The age-standardized rate (per 100,000 population) was calculated by the direct method. Standardization was crucial in this study as it eliminates the bias when comparing proportions or rates. For example, it eliminates the influence of gender, age, etc., between two groups, allowing the analysis of substantive differences. The case fatality rate (CFR) was calculated by dividing the mortality rate with the morbidity rate of the cancers, i.e.,
Cancers ranked by age-standardized deaths (a) and incidence (b) in 21 regions in 2019; and the age-standardized deaths (c) and incidence (d) of 29 specified cancer groups in 2019 by different HDI and SDI regions
The ASDRs and ASIRs of the total cancer incidences and deaths in 204 countries and territories in 2019 were statistically analyzed and are presented in Fig. 4. Forty-five countries had ASDRs greater than 150, with the highest being Mongolia, with an ASDR of close to 300 and double that of the GAL. There were 31 countries with ASDRs lower than 100, and Sri Lanka, the Syrian Arab Republic, Algeria, Maldives, Saudi Arabia, and Kuwait showed ASDRs lower than 80. Globally, China had the largest number of cancer deaths (2.71 million), followed by India and the USA, with 930,000 and 760,000, respectively. Besides, 19 countries showed ASIRs greater than 300. Canada and the USA had the highest ASIRs, exceeding 1,000, while Greenland, New Zealand, Australia, and Monaco exceeded 500. Bangladesh and Niger had the lowest morbidity rates, showing ASIRs below 100.
In this study, we assessed the global burden of 29 cancers in 2019. The analysis of the morbidity, mortality, incidences, and deaths by region, country, and gender revealed that the cancer spectrum varies widely among the different regions and countries. In addition, some cancer types were analyzed individually to quantify and clarify the burden of the specific cancers. Although the global cancer deaths exceeded 10 million in 2019, nearly onefold of the deaths in 1990, the mortality rate of cancer decreased by 15% due to the rapid global population growth. However, the global cancer incidences in 2019 were 2.3 times the number observed in 1990, an 11% increase compared to 1990. Thus, the increased morbidity of cancer observed in 2019 implies a need for better global means of cancer prevention under the current aggravating risk factors. However, the observed reduction of cancer mortality implies that the nearly 30 years of medical development from 1990 has achieved good results in cancer treatment, for example, in the treatment of stomach cancer and Hodgkin lymphoma, whose mortality declined by over 40%. The decrease in mortality from stomach cancer is mainly related to stomach cancer screening and treatment methods. For example, gastric cancer detected in the early stages can be treated radically under endoscopy, exceeding the 5-year survival rate by over 90%. In addition, the morbidity of stomach cancer had the largest decline of over 30% among all the cancers, mainly due to the decrease in the infection rate of Helicobacter pylori, salt intake, and increased intake of fresh vegetables and fruits [11, 12].
The significant differences in the cancer spectrum among regions can be attributed to the local environment, living habits, medical conditions, etc. For example, in resource-rich and developed Western countries, the morbidity and mortality of cervical cancer have slowly declined, where over 80% of cervical cancer deaths are reduced through prevention strategies and screening . However, in Africa, the morbidity and mortality rates of cervical cancer are relatively high due to the lack of established scientific and effective screening schemes for cervical cancer, low vaccination rates, the prevalence of AIDS, and limited medical resources [14, 15].
Among the cancer types, pancreatic cancer had the highest CFR; this is because pancreatic cancer is highly invasive, highly malignant, has a low resection rate, and has a very poor prognosis . Besides, it lacks specific tumor markers, making it difficult to diagnose early using the current imaging technologies, which are also unsuitable for large-scale screening. Pancreatic cancer is common in people over 50 years. Its incidences are increased by risk factors such as smoking, chronic pancreatitis, obesity, and diabetes . The pancreatic cancer risk ratio is 2.5 times more in smokers, and quitting smoking for two years reduces this risk by 48%. However, smokers must quit smoking for at least ten years for pancreatic cancer risk to drop to the level of non-smokers . Besides, type 2 diabetes has been linked to an increased risk of pancreatic cancer, where 9.7% of pancreatic cancer occurrences in Italy have been attributed to diabetes . A history of diabetes for five years or more increases the relative risk for pancreatic cancer by 2.1 times , with 8.8% of pancreatic cancer deaths been related to a high fasting plasma glucose . In addition, a high BMI index and exposure to chloride, metals and textile dust, and organic solvents increase the risk of pancreatic cancer . In addition, various types of chronic pancreatitis, including alcoholic, non-alcoholic, hereditary, and tropical, have been associated with pancreatic cancer incidences [23, 24]. Surgical resection is the only effective way to cure and give a chance of long-term survival in pancreatic cancer patients. However, more than 80% of pancreatic cancer patients miss surgery since the cancer is discovered at the terminal stages. Therefore, prevention strategies are fundamental to reduce the pancreatic cancer burden. In addition, future strategies, including comprehensive policies to control tobacco use, alcohol intake, and measures to reduce obesity and diabetes burden across the world, should be enacted. More importantly, patients with pancreatic duct stones, intraductal mucinous papillomas, cystic adenoma, and other benign pancreatic lesions should seek medical attention earliest possible. 2b1af7f3a8