Background

Cancer was one of the leading causes of death worldwide.1 High incidence rates and mortality lead to the large use of social medical resources. Kidney cancer is the 14th most common malignancy worldwide,2,3 and about 20% of the renal tumors still have metastases at the time of diagnosis.4 The incidence of kidney cancer varies widely geographically, and it was relatively higher in Europe and North America.5 Multiple factors influence the occurrence and progression of kidney cancer, including age,6 gender,7 inherited genetic factors (such as Birt–Hogg–Dube syndrome8 and hereditary leiomyomatosis and renal cell carcinoma9), lifestyle (such as smoking,10 excess body weight11 and hypertension12) and so on. The incidence rate of kidney cancer in China was about 4.99/100 000 and the mortality-to-incidence ratio was 0.37.13 The huge population base of China led to 25600 deaths due to kidney cancer in 2014.13 Therefore, understanding the kidney cancer burden and its developing status has great significance for cancer control and public health improvement.

The Global Burden of Diseases (GBD) provides epidemiological and some socioeconomic data on cancers.14 Currently, some studies have described the epidemiological characteristics of renal cancer in some countries,15–17 but the latest epidemiological study of kidney cancer in China used the kidney cancer cohort between 1992 and 2016.18 Based on the latest GBD (2019) research data, this study comprehensively describes the disease burden and risk factors of kidney cancer in China from 1990 to 2019, and predicts the development trend of incidence rate and mortality of kidney cancer in China.

Methods Data Source

We employed the suite of estimation methods for the burden of disease used in GBD 2019 to assess the state of population health in China, from 1990 to 2019. Previous researches had elaborated the data collection and analysis methods in full detail.19,20 The epidemiological information on kidney cancer was collected from the Global Health Data Exchange (GHDx, http://ghdx.healthdata.org/gbd-results-tool), including age-sex-specific incidence, mortality and disability-adjusted life-years (DALYs) rates. We used the following criteria (“China” as the location, “kidney cancer”, “incidence”, “death” and “DALYs”) to retrieve data from the online database. Meanwhile, we analyzed the regional DALYs and age-standardized DALY rate (ASDR) of each province of kidney cancer in China through the data in 2017 to further express the sub-national disease burden difference of kidney cancer in China.21 The 34 provincial administrative units were divided into four groups (low-middle, middle, high-middle, and high) according to the socio-demographic index (SDI). SDI is a combined average of the incomes per capita, average educational attainment, and fertility rates of all regions included in the GBD study.

Risk Factor Analysis

Eighty-seven risk factors were identified in the GBD 2019 study, including the following four categories: environmental and occupational, behavioral, metabolic, and dietary risks.22,23 The proportion of DALYs attributable to risk factors by sex and year was evaluated by the comparative risk assessment (CRA) framework.22 Usually, the framework consists of six steps: (1) identifying strong risk–outcome pairs, (2) estimating relative risks, (3) assessing exposure levels and distribution, (4) determining the theoretical minimum exposure level, (5) calculating the population attributable proportion, and (6) assessing attributable proportion for combined risk factors by considering the mediating effect.

Statistical Analyses

The descriptive analysis of the incidence rate, mortality and DALYs of kidney cancer was conducted by 5-year-old age group, gender, and year. These indicators plot temporal trends from 1990 to 2019. Age was grouped by 5-year period, ranging from under 5 to over 95, a total of 20 specific age groups. Referring to the previous research, we chose the GBD world population age standard to calculate the age-standard rate for the incidence, mortality, and DALYs of kidney cancer.24,25 The time trends of age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and ASDR were calculated by estimated annual percentage change (EAPC). The EAPC is summative and was widely used to measure the secular trend over a given interval. The EAPC was calculated as 100 × (exp(β) − 1), and its 95% confidence interval (CI) was also obtained from the linear regression model.26–28 BAPC (Bayesian age-period cohort) and INLA (integrated nested Laplace approximation) packages in R were used for analyzation of the Bayesian age-period-cohort model. We calculated the absolute number of events that would occur if rates had remained stable (baseline reference), with a 2% decrease per year (optimistic reference) or an increase per year (pessimistic reference), to facilitate comparison with predictions. A P < 0.05 was recognized as statistically significant.29

Results Current Kidney Cancer Burden in China

In 2019, there were 59.83 thousand (95% UI: 49.51, 71.24) incident cases of kidney cancer for the total Chinese population, and the ASIR was 3.21 per 100,000 (95% UI: 2.7, 3.79) (Table 1). Kidney cancer contributed to 23.95 thousand (95% UI: 19.77, 28.48) deaths, and the ASMR of the total population was 1.27 per 100,000 (95% UI: 1.05, 1.49) (Table 2). Kidney cancer caused 642.8 thousand (95% UI: 533.66, 763.98) DALYs, and the ASDR was 34.28 per 100,000 (95% UI: 28.95, 40.16) (Table 3). The incidence, mortality, DALYs and ASIR were about 2.5 times higher in men than in women (Tables 1–3).

Table 1 The Number of Incident Cases and the Age‐standardized Incidence Rates of Kidney Cancer in China in 1990 and 2019 and the Estimated Annual Percentage Changes from 1990 to 2019

Table 2 The Number of Deaths and the Age‐standardized Mortality Rates of Kidney Cancer in China in 1990 and 2019 and the Estimated Annual Percentage Changes from 1990 to 2019

Table 3 The Number of DALYs and the Age‐standardized DALYs Rates of Kidney Cancer in China in 1990 and 2019 and the Estimated Annual Percentage Changes from 1990 to 2019

The number of incident cases, deaths and DALYs varies by age group. In 2019, the number of incident cases and DALYs of kidney cancer peaked between 50 and 54 years in males (Table 1 and Figure 1). The number of incident cases and DALYs of females and the number of deaths of both sexes of kidney cancer peaked 65–69 years (Table 1 and Figure 1).

Figure 1 Disease burden of kidney cancer in 2019 in China. Numbers and rates of incidence (A), mortality (B), and DALYs (C) of kidney cancer by age and sex in 2019 in China. Shading represents the upper and lower limits of the 95% uncertainty intervals (95% UIs). DALYs, disability-adjusted life-years.

The ASIR, ASMR and ASDR also varied with age, and they peaked at 85–89 years among the total population (Tables 1–3). They presented similar trends among both sexes. Due to the peak incidence of Wilms tumor originating from embryonic cells, the incidence rate and mortality of kidney cancer reached a “sub-peak” under 5 years compared with other age groups under 35 years (Tables 1–3 and Figure 1).

Temporal Trends in Kidney Cancer Incidence, Mortality, and DALYs Rates Over Time

For the total population, the absolute number of new cases and deaths had a significant increase from 1990 to 2019, and so does the DALYs (Tables 1–3). The ASIR increased from 1.16 per 100,000 (95% CI: 1.02, 1.31) in 1990 to 3.21 per 100,000 (95% CI: 2.7, 3.79) in 2019, with an EAPC of 4.46 (95% CI: 3.95, 4.98) (Table 1). ASIR increased more significantly in men than in women during this period (EAPC=5.46, CI: (4.88, 6.04) vs EAPC=2.80, CI: (2.38, 3.23), respectively) (Table 1 and Figure 2C). At most ages, the incidence rates presented upward trends among both females and males. The number of incident cases increased by 4 to 14 times among the population over 30 years (Table 1 and Figure 2A). The incidence rate per 100,000 population increased by 2–4 times among the ≥10 years old group, especially among males (Table 1 and Figure 2B).

Figure 2 Temporal trends in kidney cancer burden from 1990 to 2019 in China. The number of incident cases (A), incidence rate (B) of kidney cancer by age and sex, from 1990 to 2019 in China; EAPC of incidence rate (C) of kidney cancer by age and sex in 2019 in China. EAPC, estimated annual percentage change.

The ASMR increased from 0.7 per 100,000 (95% CI: 0.61, 0.79) to 1.27 per 100,000 (95% CI: 1.05, 1.49) from 1990 to 2019, with an EAPC of 2.79 (95% CI: 2.3, 3.26) (Table 2). In this period, it observed an increasing trend of ASDR and the EAPC was 2.28 (95% CI: 1.83, 2.73) (Table 3). It also observed overall upward trends in ASMR and ASDR in age groups ≥10 years among both sexes (Figure S1), with about 2 times increasing among both sexes ≥30 years old (Table 2, Table 3, Figure S1).

Province-Level Burden of Kidney Cancer in China

In addition, we summarized the ASDRs and their changes for 33 provinces. In 2017, the age-standardized DALY rates were highest in Taiwan, Tianjin, Liaoning, Shanghai, and Beijing, which showed two- to three-fold differences compared with the lowest rates in Macau SAR, Hainan, Guangdong, Chongqing and Yunnan (Figure 3A). The ASDR in northern and eastern China is generally higher than that in southern and western China. The ASDR is related to the local SDI (Figure 3B). Comparing the changes in the ASDR of kidney cancer between 1990 and 2017, it had increased in most provinces except Macau SAR (Figure 3, Figure S2). Among them, the ASDR in Taiwan, Liaoning, and Tianjin increased quickly and the ASDR in Tibet, Guizhou, Qinghai, and Ningxia increased slowly.

Figure 3 The province-level burden of kidney cancer in 2017 in China. Age-standardized DALY rate per 100,000 population by the province of China in 2017 (A) and age-standardized DALY rates for kidney cancer and SDI by province, for 2017 (B). DALY, disability-adjusted life-years, ASDR, age-standardized DALY rate, SDI, social-demographic index.

Risk Factors for Kidney Cancer

In all age-specific groups, smoking among males, high body mass index among females, and high body mass index among males were the first three contributions to DALYs. The proportions of DALYs attributed to smoking, high body mass index, and occupational exposure to trichloroethylene differed between genders. The most significant contribution to DALYs for males was smoking, accounting for more than 19.5% from 1990 to 2019. The contribution of smoking to kidney cancer DALYs was about 10 times higher for males than that for females. However, a high body mass index more significantly contributed to DALYs among females than that of males. Occupational exposure to trichloroethylene accounted for the lowest proportion of DALYs in both sexes (Figure 4A). Age-specific groups analysis indicated that smoking had a great impact on the elderly male groups and occupational exposure to trichloroethylene had a great impact on middle-aged groups. The influence of high body mass index did not show a significant difference between age-specific groups (Figure 4B). Increased trends of DALYs attributable to smoking and high body mass index were observed in the elderly population and males (Figure S3). Therefore, smoking was the most significant contributor, and the high body mass index was the most increasing risk factor.

Figure 4 Risk factor analysis for kidney cancer in China. Proportions of DALYs of kidney cancer attributable to risk factors by sex from 1990 to 2019 in China (A); and proportions of DALYs attributable to risk factors by age and sex in 2019 in China (B). DALYs, disability-adjusted life-years.

Predictions of Kidney Cancer Incidence and Death Rates in China

Based on the kidney cancer data from the GBD database from 1990 to 2019 in China, the disease burden in the next 10 years was further predicted. Our projection indicated that the rates of incidence, mortality, and the number of new cases and deaths would continue to increase in both sexes in the next decade. It is predicted that the ASIR will increase significantly in the next 10 years, especially for males (EAPC = 4.25 for males; EAPC = 2.60 for females) (Figure 5A and C). In contrast, the growth rate for ASMR somewhat slowed for both sexes over the next decade (EAPC = 2.14 for males; EAPC = 1.20 for females) (Figure 5B and D). In 2030, the predicted ASIR and ASMR of kidney cancer would increase to 7.53 per 100,000 and 2.46 per 100,000 in men, and 2.54 per 100,000 and 0.82 per 100,000 in women, respectively. In addition, although it is expected that the number of new cases and deaths of kidney cancer in China were expected to continue to increase in the next decade (126.8 thousand incident cases and 41.8 thousand deaths by 2030), the number of increased cases will be mainly male, and only slightly female (Figure 5E and F).

Figure 5 Predictions of kidney cancer incidence and death rates in China until 2030. Temporal trends and projected age-standardized incidence rate and age-standardized death rate by sex, from 1990 to 2030 in China (A and B for male, C and D for female); Trends in observed (dashed lines) and projected (solid lines) kidney cancer in the number of incidence cases (E) and deaths (F) from 1990 to 2030. Shading represents a 2% decreasing and increasing interval based on the 2019 rate.

Discussion

Using the latest GBD 2019 data, this study reported the disease burden of renal cancer in China, and analyzed the risk factors and the time trend of incidence rate, mortality and DALYs rate of renal cancer in China. In 2019, there were about 5.983 million new cases of kidney cancer and 2.395 million deaths in China. The ASIR was 3.21 per 100,000 and the ASMR was 1.27 per 100,000. Our study indicated that the ASIR of renal cancer in males was higher than that in females, and the difference will continue into the next decade. Smoking was the most important risk factor for male renal cancer, while the high body mass index was the important risk factor for both sexes.

The ASDR of kidney cancer varied across provinces in China. The inter-provincial differences burden of kidney cancer may be partly because of the different distribution of risk factors.30 Smoking is relatively more prevalent in southern provinces, such as Yunnan, Hunan, and Guizhou, compared with others.31 However, the kidney cancer burden distribution is significantly different from that of smoking. High body mass index was another risk factor for renal cancer. The body mass index of people in northern China is generally higher than that in other regions of China,32 which is consistent with the distribution of ASDR of kidney cancer. In addition, this study indicated that the distribution of the kidney cancer burden was related to the level of regional economic development. Previous studies showed that the body mass index was positively correlated with economic income,33 which might be the reason.

Consistent with previous studies, we found the incidence of renal cancer in men is significantly higher than that in women,6 and so do the ASIR, ASMR and DALYs. It also showed that the cancer burden gap between males and females was and will be increasing from 1990 to 2030. Smoking is an important risk factor for renal cell carcinoma. The significantly higher prevalence of smoking among males (57.4%) compared with females (2.6%) may help explain the huge incidence gap.34 Researches showed that hormone level contributes to the occurrence and development of kidney cancer. Overexpression of androgen receptor (AR) promoted the occurrence, invasion and migration of kidney cancer.35 Lee et al found histone demethylase 1 affects kidney cancer progression by regulating androgen receptor activity.36 In addition, studies found expression of estrogen receptor β (ERβ) increases with tumor stage and grade and ERβ increases ccRCC stem cell phenotype, and estrogens can reduce RCC tumor growth and invasion significantly in mouse models.37,38 This suggested that gender might be an independent risk factor for kidney cancer.39

Smoking is one of the most important risk factors for kidney cancer, especially for men. The risk of kidney cancer among male ever smokers was higher compared to female ones.40 Liu et al found that the risk of renal cancer increased nonlinearly with the increase in smoking intensity, and the risk increased sharply under relatively low smoking intensity.41 Previous studies have shown that the susceptibility of renal cell carcinoma caused by smoking is related to a gene mutation on chromosome 3p, and it has been found von Hippel Lindau gene on chromosome 3p is one of the earliest and most common mutation sites in renal cell carcinoma.42,43 In addition, oxygen free radicals generation and oxidative DNA damage may promote the pathogenesis of smoking-related renal cancer.44,45 Long-term exposure to nicotine and other chemical substances increases protein kinase B expression and angiogenesis, which is conducive to the proliferation of cancer cells and the progression of kidney cancer.46

High body index mass was another risk factor of kidney cancer, especially for females. The tissue hypoxia, increasing adipose stromal cells, changing of immune microenvironment, and the increase of fatty acids caused by obesity may contribute to the development of kidney cancer.47 However, Obesity not only increases the risk of RCC development but also decreases the risk of recurrence and increases overall survival 48–51, which is called the “obesity paradox”. Albiges et al reported that high body mass index is related to better overall survival and progression-free survival.52 The cause of this phenomenon is still unclear, so further studies are needed to explore its potential mechanism.

The persistent upsurge in the incidence of kidney cancer in China can be partially attributed to the recent advancements in diagnostic modalities that have facilitated a greater rate of early detection53 and stage T1 tumors accounted for the majority.54 In Europe, similarly, the proportion of patients diagnosed with early-stage RCC has experienced an upward trend over the past few decades, owing to the influence of stage migration.55 Besides, it is similar to the epidemiological trend of kidney cancer in China that the incidence, mortality, ASIR and ASMR increased in most European Union (EU) 15+ countries and World Health Organization (WHO) regions from 1990 to 2019.56 Chinmay et al also reported the mortality-to-incidence ratio (MIR) decreased in all EU countries and WHO regions. Although MIR was not evaluated in this article, we predicted the growth rate for ASMR somewhat slowed for both sexes over the next decade, which may bring a slowdown in MIR.

The incidence of kidney cancer is still rising in China. As the trend of the elderly population increases in China,57 the incidence of kidney cancer will further increase and bring considerable pressure on the public health system in China. To reduce the incidence of kidney cancer, the top priority in China is to control the body mass index and smoking rates of the population.58 The government should fully promote the smoke-free policy and actively publicize the harm of tobacco. With the development of the economy and the improvement of income level, the body mass index of Chinese people is on the rise. The government should widely advocate a healthy diet and promote nationwide fitness. At the same time, the application of a screening program, which integrates abdominal ultrasound scans and the analysis of urinary biomarkers, may be beneficial in enabling the early detection of kidney cancer and facilitating the administration of minimally invasive surgical therapies.59 It is similar to most health problems, that promoting early prevention and screening programs is the most important and economic measure for renal cancer prevention.

This study still has some limitations. Firstly, the data provided by GBD 2019 comes from different sources, and the quality of the original data may affect the results of this study. Although various mathematical models were used in this study to correct the data, the effects cannot be ignored. Secondly, the study did not involve the impact of other risk factors such as genetic factors on the burden of renal cancer. Thirdly, this study mainly involved renal cell carcinoma. Other histological classifications, such as ccRCC and pRCC, although their oncological characteristics and prognosis are different, due to their low incidence, did not make the separate analysis.

Conclusions

In conclusion, the total burden of kidney cancer increased gradually over the latest 30 years, and it would still increase in the next decade, especially for males, in China. Smoking and high body mass index are the most important risk factors for renal cell carcinoma, and the influence of high body mass index is increasing year by year. We should formulate detailed and targeted prevention and control strategies, such as health education publicity and high-risk population screening, to reduce the socioeconomic pressure brought by kidney cancer.

Abbreviations

DALYs, disability-adjusted life-years; EAPC, estimated annual percentage change; ASIR, age-standardized incidence rate; RCC, renal cell carcinoma; ccRCC, clear cell RCC; pRCC, papillary RCC; GBD, Global Burden of Diseases; GHDx, Global Health Data Exchange; ASDR, age-standardized DALY rate; SDI, socio-demographic index; CRA, comparative risk assessment; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; CI, confidence interval; BAPC, Bayesian age-period cohort; INLA, integrated nested Laplace approximation; AR, androgen receptor; STAT5, signal transducer and activator of transcription 5; BARE trial, Blockade of Androgens in Renal cell carcinoma using Enzalutamide; EU, European Union; WHO, World Health Organization; MIR, mortality-to-incidence ratio.

Data Sharing Statement

The GBD 2019 study is a publicly available database (http://ghdx.healthdata.org/gbd-2019), and we fully complied with the GBD data usage requirements.

Ethics Approval and Consent to Participate

The GBD 2019 study is a publicly available database, and all data were anonymous. Our study protocol was approved by the Institutional Review Boards of Qilu Hospital of Shandong University with approval number KYLL-202011(KS)-239.

Consent for Publication

Not applicable due to no individual information.

Acknowledgments

We would like to thank the institute for Health Metrics and Evaluation staff and the GBD collaborators who prepared these publicly available data.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by the National Natural Science Foundation of China (82103912); the China Postdoctoral Science Foundation (2021M700080); and the Shandong Provincial Natural Science Foundation (ZR2020QH302). The funders were not involved in the collection, analysis, or interpretation of data, or the writing or submitting of this report.

Disclosure

All authors declare that they have no competing interests.

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