Changfa Xia

Cancer incidence and mortality in China in 2013: an analysis based on urbanization level

Objective To explore the cancer patterns in areas with different urbanization rates (URR) in China with data from 255 population-based cancer registries in 2013, collected by the National Central Cancer Registry (NCCR). Methods There were 347 cancer registries submitted cancer incidence and deaths occurred in 2013 to NCCR. All those data were checked and evaluated based on the NCCR criteria of data quality, and qualified data from 255 registries were used for this analysis. According to the proportion of non-agricultural population, we divided cities/counties into 3 levels: high level, with URR equal to 70% and higher; median level, with URR between 30% and 70%; and low level, with URR equal to 30% and less. Cancer incidences and mortalities were calculated, stratified by gender and age groups in different areas. The national population of Fifth Census in 2000 and Segi’s population were applied for age-standardized rates. Results Qualified 255 cancer registries covered 226,494,490 populations. The percentage of cases morphologically verified (MV%) and death certificate-only cases (DCO%) were 68.04% and 1.74%, respectively, and the mortality to incidence rate ratio (M/I) was 0.62. A total of 644,487 new cancer cases and 399,275 cancer deaths from the 255 cancer registries were submitted to NCCR in 2013. The incidence rate was 284.55/100,000 (314.06/100,000 in males, 254.19/100,000 in females), and the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.10/100,000 and 186.24/100,000 with the cumulative incidence rate (0–74 age years old) of 21.60%. The cancer mortality was 176.28/100,000 (219.03/100,000 in males, 132.30/100,000 in females), and the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 110.91/100,000 and 109.92/100,000, and the cumulative mortality rate (0–74 age years old) was 12.43%. Low urbanization areas were high in crude cancer incidence and mortality rates, middle urbanization areas came next to it followed by high urbanization areas. After adjusted by age, there was a U-shaped association between age-standardized incidence (ASIRC and ASIRW) and the urbanized ratio with the middle urbanization areas having the lowest ASIRC and ASIRW. Unlike with the age-standardized incidence, the sort order of age-standardized mortality (ASMRC and ASMRW) among three urbanization areas was reversed completely from the crude mortality. Lung cancer was the most common cancer in all areas of 255 cancer registries, followed by stomach cancer, liver cancer, colorectal cancer and esophageal cancer with new cases of 130,700, 76,200, 63,800, 60,900 and 50,200 respectively. Lung cancer was also the leading cause of cancer death in all areas of 255 cancer registries for both males and females with the number of deaths of 72,200 and 34,100, respectively. Other cancer types with high mortality in males were liver cancer, stomach cancer, esophageal cancer and colorectal cancer. In females, stomach cancer was the second cause of cancer death, followed by liver cancer, colorectal cancer and breast cancer. Conclusions Along with the development of socioeconomics associated with urbanization, as well as the aging population, the incidence and mortality keep increasing in China. Cancer burden and patterns are different in each urbanization level. Cancer control strategies should be implemented referring to local urbanization status.

Environmental factors, seven GWAS-identified susceptibility loci, and risk of gastric cancer and its precursors in a Chinese population

Gene–environment interactions may increase gastric cancer (GC) risk. Seven susceptibility loci identified by genome‐wide association studies (GWASs) suggest that genetic factors play a role in gastric carcinogenesis. Meanwhile, Helicobacter pylori (H. pylori) infection, smoking, and alcohol drinking are also important environmental factors for gastric cancer. However, studies to explore the role of gene–environment interactions in gastric carcinogenesis, and particularly the relationship between the seven susceptibility loci and their potential interactions with H. pylori infection, smoking, and alcohol drinking in risk of GC, and severe intestinal metaplasia (IM)/dysplasia, have been inconclusive. A total of 1273 subjects in a Chinese population were recruited, and genotyping was carried out using the competitive allele‐specific PCR (KASP) method. Unconditional logistic regression was applied to model the associations between genetic polymorphisms and the disease risk. Effect modifications by H. pylori infection, smoking and alcohol drinking were evaluated. PSCA rs2294008/rs2976392 showed a significant, multiplicative interaction with H. pylori infection in risk of GC. Meanwhile, PRKAA1 rs13361707 had an additive interaction with H. pylori infection. SLC52A3 rs13042395 showed an interaction with alcohol drinking in risk of GC. Moreover, three SNPs, MUC1 rs4072037, ZBTB20 rs9841504 and PRKAA1 rs13361707, were associated with precancerous gastric lesions (severe IM/dysplasia). Our data suggest that genetic predisposition factors identified by GWAS may interact with environmental risk factors, Particularly for H. pylori infection and alcohol consumption, to increase the risk of GC.

Temporal Trends in Geographical Variation in Breast Cancer Mortality in China, 1973–2005: An Analysis of Nationwide Surveys on Cause of Death

To describe geographical variation in breast cancer mortality over time, we analysed breast cancer mortality data from three retrospective national surveys on causes of death in recent decades in China. We first calculated the age-standardized mortality rate (ASMR) for each of the 31 provinces in mainland China stratified by survey period (1973–1975, 1990–1992 and 2004–2005). To test whether the geographical variation in breast cancer mortality changed over time, we then estimated the rate ratio (RR) for the aggregated data for seven regions and three economic zones using generalized linear models. Finally, we examined the correlation between mortality rate and several macro-economic measures at the provincial level. We found that the overall ASMR increased from 2.98 per 100,000 in 1973–1975 to 3.08 per 100,000 in 1990–1992, and to 3.85 per 100,000 in 2004–2005. Geographical variation in breast cancer mortality also increased significantly over time at the regional level (p = 0.002) but not at the economic zone (p = 0.089) level, with RR being generally lower for Western China (Northwest and Southwest) and higher in Northeast China over the three survey periods. These temporal and spatial trends in breast cancer mortality were found to be correlated with per capita gross domestic product, number of hospitals and health centres’ beds per 10,000 population and number of practicing doctors per 10,000 population, and average number of live births for women aged 15–64. It may be necessary to target public health policies in China to address the widening geographic variation in breast cancer mortality, and to take steps to ensure that the ease of access and the quality of cancer care across the country is improved for all residents.

Changing cancer survival in China during 2003–15: a pooled analysis of 17 population-based cancer registries

BACKGROUND From 2003 to 2005, standardised 5-year cancer survival in China was much lower than in developed countries and varied substantially by geographical area. Monitoring population-level cancer survival is crucial to the understanding of the overall effectiveness of cancer care. We therefore aimed to investigate survival statistics for people with cancer in China between 2003 and 2015. METHODS We used population-based data from 17 cancer registries in China. Data for the study population was submitted by the end of July 31, 2016, with follow-up data on vital status obtained on Dec 31, 2015. We used anonymised, individual cancer registration records of patients (aged 0-99 years) diagnosed with primary, invasive cancers from 2003 to 2013. Patients eligible for inclusion had data for demographic characteristics, date of diagnosis, anatomical site, morphology, behaviour code, vital status, and last date of contact. We analysed 5-year relative survival by sex, age, and geographical area, for all cancers combined and 26 different cancer types, between 2003 and 2015. We stratified survival estimates by calendar period (2003-05, 2006-08, 2009-11, and 2012-15). FINDINGS There were 678 842 records of patients with invasive cancer who were diagnosed between 2003 and 2013. Of these records, 659 732 (97·2%) were eligible for inclusion in the final analyses. From 2003-05 to 2012-15, age-standardised 5-year relative survival increased substantially for all cancers combined, for both male and female patients, from 30·9% (95% CI 30·6-31·2) to 40·5% (40·3-40·7). Age-standardised 5-year relative survival also increased for most cancer types, including cancers of the uterus (average change per calendar period 5·5% [95% CI 2·5-8·5]), thyroid (5·4% [3·2-7·6]), cervix (4·5% [2·9-6·2]), and bone (3·2% [2·1-4·4]). In 2012-15, age-standardised 5-year survival for all patients with cancer was higher in urban areas (46·7%, 95% CI 46·5-47·0) than in rural areas (33·6%, 33·3-33·9), except for patients with oesophageal or cervical cancer; but improvements in survival were greater for patients residing in rural areas than in urban areas. Relative survival decreased with increasing age. The increasing trends in survival were consistent with the upward trends of medical expenditure of the country during the period studied. INTERPRETATION There was a marked overall increase in cancer survival from 2003 to 2015 in the population covered by these cancer registries in China, possibly reflecting advances in the quality of cancer care in these areas. The survival gap between urban and rural areas narrowed over time, although geographical differences in cancer survival remained. Insight into these trends will help prioritise areas that need increased cancer care. FUNDING National Key R&D Program of China, PUMC Youth Fund and the Fundamental Research Funds for the Central Universities, and Major State Basic Innovation Program of the Chinese Academy of Medical Sciences.

Evaluating efficacy of screening for upper gastrointestinal cancer in China: a study protocol for a randomized controlled trial

Objective To evaluate the efficacy and feasibility of screening procedure for upper gastrointestinal cancer in both high-risk and non-high-risk areas in China. Setting Seven cities/counties, representing three economical-geographical regions (Eastern, Central and Western) in China, were selected as screening centers: three in high-risk areas and four in non-high-risk areas. Participants Villages/communities in these seven centers regarded as clusters were randomly assigned to either intervention group (screening by endoscopic examination) or control group (with normal community care) in a 1:1 ratio stratified by each center. Eligible participants are local residents aged 40–69 years in the selected villages/communities with no history of cancer or endoscopic examination in the latest 3 years who are mentally and physically competent. Those who are not willing to take endoscopic examination or are unwilling to sign the consent form are excluded from the study. Totally 140,000 participants will be enrolled. Interventions In high-risk areas of upper gastrointestinal cancer, all subjects in screening group will be screened by endoscopy. In non-high-risk areas, 30% of the subjects in screening group, identified through a survey, will be screened by endoscopy. Primary and secondary outcome measures The primary outcome is the mortality caused by upper gastrointestinal cancer. The secondary outcomes include detection rate, incidence rate, survival rate, and clinical stage distribution. Additional data on quality of life and cost-effectiveness will also be collected to answer important questions regarding screening effects. Conclusions Screening strategy evaluated in those areas with positive findings may be promoted nationally and applied to the majority of Chinese people. On the other hand, negative findings will provide scientific evidence for abandoning a test and shifting resources elsewhere. Trial registration The study has been registered with the Protocol Registration System in Chinese Clinical Trial Registry (identifier: ChiCTR-EOR-16008577).

Comparison of cancer incidence and mortality in three GDP per capita levels in China, 2013

Objective In this research, the patterns of cancer incidence and mortality in areas with different gross domestic product per capita (GDPPC) levels in China were explored, using data from population-based cancer registries in 2013, collected by the National Central Cancer Registry (NCCR). Methods Data from 255 cancer registries were qualified and included in this analysis. Based on the GDPPC data of 2014, cities/counties were divided into 3 levels: high-, middle- and low-GDPPC areas, with 40,000 and 80,000 RMB per year as cut points. We calculated cancer incidences and mortalities in these three levels, stratified by gender and age group. The national population of the Fifth Census in 2000 and Segis population were applied for age-standardized rates. Results The crude incidence and mortality rates as well as age-standardized incidence rate (ASIR) showed positive associations with GDPPC level. The age-standardized mortality rate (ASMR) nevertheless showed a negative association with GDPPC level. The ASMR in high-, middle- and low-GDPPC areas was 103.12/100,000, 112.49/100,000 and 117.43/100,000, respectively. Lung cancer was by far the most common cancer in all three GDPPC levels. It was also the leading cause of cancer death, regardless of gender and GDPPC level. Negative associations with GDPPC level were found for the ASIRs of lung, stomach, esophageal and liver cancer, whereas colorectal and breast cancer showed positive associations. Except for breast cancer, the ASMRs of the other five cancers were always higher in middle- and low-GDPPC areas than in high-GDPPC areas. Conclusions The economic development is one of the main factors of the heavy cancer burden on Chinese population. It would be reasonable to implement cancer control strategies referring to the local GDPPC level.

Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013

Background The burden of cancer in China is high, and it is expected to further increase. Information on cancers attributable to potentially modifiable risk factors is essential in planning preventive measures against cancer. We estimated the number and proportion of cancer deaths and cases attributable to ever-smoking, second-hand smoking, alcohol drinking, low fruit/vegetable intake, excess body weight, physical inactivity, and infections in China, using contemporary data from nationally representative surveys and cancer registries. Methods The number of cancer deaths and cases in 2013 were obtained from the National Central Cancer Registry of China and data on most exposures were obtained from the China National Nutrition and Health Survey 2002 or 2006 and Global Adult Tobacco Smoking 2010. We used a bootstrap simulation method to calculate the number and proportion of cancer deaths and cases attributable to risk factors and their corresponding 95% confidence intervals (CIs), allowing for uncertainty in data. Results Approximately 718 000 (95% CI 702 100-732 200) cancer deaths in men and 283 100 (278 800-288 800) cancer deaths in women were attributable to the studied risk factors, accounting for 52% of all cancer deaths in men and 35% in women. The numbers for incident cancer cases were 952 500 (95% CI 934 200-971 400) in men and 442 700 (437 200-447 900) in women, accounting for 47% of all incident cases in men and 28% in women. The greatest proportions of cancer deaths attributable to risk factors were for smoking (26%), HBV infection (12%), and low fruit/vegetable intake (7%) in men and HBV infection (7%), low fruit/vegetable intake (6%), and second-hand smoking (5%) in women. Conclusions Effective public health interventions to eliminate or reduce exposure from these risk factors, notably tobacco control and vaccinations against carcinogenic infections, can have considerable impact on reducing the cancer burden in China.

Trends in geographical disparities for cervical cancer mortality in China from 1973 to 2013: a subnational spatio-temporal study

Objective This study was designed to explore the time trends in geographical variations of cervical cancer mortality in mainland China over the period 1973 to 2013, to provide subnational spatio-temporal patterns for targeted promotion of human papillomavirus vaccine in China. Methods Data were extracted from three national retrospective death surveys and cancer registry. The rate ratio (RR) was estimated for the aggregated data for seven geographical regions using generalized linear models to evaluate time trends in geographical disparities of cervical cancer mortality. Results There was a significant decrease in cervical cancer mortality in China from 1973-1975 to 2004-2005, but leveled off thereafter to 2011-2013. Compared to the period 1973-1975 the RR for the three last time periods were 0.33 [95% confidence interval (95% CI): 0.30-0.37] for 1990-1992, 0.21 (95% CI: 0.19-0.24) for 2004-2005 and 0.24 (95% CI: 0.22-0.26) for 2011-2013. Females living in the Northwest China and Central China have a high risk of mortality from cervical cancer compared to the nationwide, with the RR being 2.09 (95% CI: 1.83-2.38) and 1.26 (95% CI: 1.11-1.44) respectively, while the RRs for South China, Northeast China and Southwest China were below 1.00, indicating the lower death risk. Despite the mortality rate had increased slightly from 2004 to 2013, there was an encouraging sign that the geographical disparities in cervical cancer mortality had gradually narrowed over time across China. Conclusions Although cervical cancer mortality in China has reduced to very low levels, the high risk of cervical cancer in Northwest China and Central China is still noteworthy. Public health policies including the promotion of vaccine should be targeted to further reduction of geographical disparities in cervical cancer mortality.

Provincial-level cancer burden attributable to active and second-hand smoking in China

Background Understanding disparities in the burden of cancer attributable to smoking is crucial to inform and improve tobacco control measures. In this report, we estimate the population attributable fraction (PAF) of cancers deaths attributable to smoking at the national and provincial levels in China. Methods Using cancer mortality data from 978 counties, smoking data from a nationwide survey and relative risks from a prospective study of 0.5 million adults in China, we calculated the absolute (non-standardised) and standardised numbers and proportions of cancer deaths among adults 30 years and older attributable to active and second-hand smoking in 2014 across all 31 provinces in Mainland China. Results The estimated number of cancer deaths attributable to smoking in China in 2014 was 342 854 among men and 40 313 among women, of which second-hand smoking accounted for 1.8% and 50.0%, respectively. Among men, the absolute PAF in China was 23.8%, ranging from 14.6% in Xinjiang to 26.8% in Tianjin; the overall standardised PAF was 22.2%, ranging from 15.7% in Xinjiang to 26.0% in Guizhou. Among women, the overall absolute and standardised PAFs were 4.8% and 4.0%, ranging from 1.8% and 1.6% in Jiangxi to 14.9% and 9.6% in Heilongjiang, respectively. Overall, provinces with the highest standardised PAFs among men were located in Southwest China and among women in the Northeast. Conclusions Comprehensive smoke-free policies in China should expand to all provinces, notably those with a higher burden of cancer attributable to smoking, instead of being mostly limited to Beijing and some other metropolitan areas.

Annual cost of illness of stomach and esophageal cancer patients in urban and rural areas in China: A multi-center study

Objective Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereas there were few studies on the financial burden of the two cancers. Methods Costs per hospitalization of all patients with stomach or esophageal cancer discharged between September 2015 and August 2016 in seven cities/counties in China were collected, together with their demographic information and clinical details. Former patients in the same hospitals were sampled to collect information on annual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost was obtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness (ACI) was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost, stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalization were itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars (1 USD=6.6423 RMB). Results Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urban patients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancer patients were