Development and evaluation of a risk assessment tool for the personalized screening of breast cancer in Chinese populations: A prospective cohort study.

INTRODUCTION: Breast cancer is a significant contributor to female mortality, exerting a public health burden worldwide, especially in China, where risk-prediction models with good discriminating accuracy for breast cancer are still scarce. METHODS: A multicenter screening cohort study was conducted as part of the Cancer Screening Program in Urban China. Dwellers aged 40-74 years were recruited between 2014 and 2019 and prospectively followed up until June 30, 2021. The entire data set was divided by year of enrollment to develop a prediction model and validate it internally. Multivariate Cox regression was used to ascertain predictors and develop a risk-prediction model. Model performance at 1, 3, and 5 years was evaluated using the area under the curve, nomogram, and calibration curves and subsequently validated internally. The prediction model incorporates selected factors that are assigned appropriate weights to establish a risk-scoring algorithm. Guided by the risk score, participants were categorized into low-, medium-, and high-risk groups for breast cancer. The cutoff values were chosen using X-tile plots. Sensitivity analysis was conducted by categorizing breast cancer risk into the low- and high-risk groups. A decision curve analysis was used to assess the clinical utility of the model. RESULTS: Of the 70,520 women enrolled, 447 were diagnosed with breast cancer (median follow-up, 6.43 [interquartile range, 3.99-7.12] years). The final prediction model included age and education level (high, hazard ratio [HR], 2.01 [95% CI, 1.31-3.09]), menopausal age (≥50 years, 1.34 [1.03-1.75]), previous benign breast disease (1.42 [1.09-1.83]), and reproductive surgery (1.28 [0.97-1.69]). The 1-year area under the curve was 0.607 in the development set and 0.643 in the validation set. Moderate predictive discrimination and satisfactory calibration were observed for the validation set. The risk predictions demonstrated statistically significant differences between the low-, medium-, and high-risk groups (p < .001). Compared with the low-risk group, women in the high- and medium-risk groups posed a 2.17-fold and 1.62-fold elevated risk of breast cancer, respectively. Similar results were obtained in the sensitivity analyses. A web-based calculator was developed to estimate risk stratification for women. CONCLUSIONS: This study developed and internally validated a risk-adapted and user-friendly risk-prediction model by incorporating easily accessible variables and female factors. The personalized model demonstrated reliable calibration and moderate discriminative ability. Risk-stratified screening strategies contribute to precisely distinguishing high-risk individuals from asymptomatic individuals and prioritizing breast cancer screening. PLAIN LANGUAGE SUMMARY: Breast cancer remains a burden in China. To enhance breast cancer screening, we need to incorporate population stratification in screening. Accurate risk-prediction models for breast cancer remain scarce in China. We established and validated a risk-adapted and user-friendly risk-prediction model by incorporating routinely available variables along with female factors. Using this risk-stratified model helps accurately identify high-risk individuals, which is of significant importance when considering integrating individual risk assessments into mass screening programs for breast cancer. Current clinical breast cancer screening lacks a constructive clinical pathway and guiding recommendations. Our findings can better guide clinicians and health care providers.

Calcium Phosphate-Based Nanomaterials: Preparation, Multifunction, and Application for Bone Tissue Engineering.

Calcium phosphate is the main inorganic component of bone. Calcium phosphate-based biomaterials have demonstrated great potential in bone tissue engineering due to their superior biocompatibility, pH-responsive degradability, excellent osteoinductivity, and similar components to bone. Calcium phosphate nanomaterials have gained more and more attention for their enhanced bioactivity and better integration with host tissues. Additionally, they can also be easily functionalized with metal ions, bioactive molecules/proteins, as well as therapeutic drugs; thus, calcium phosphate-based biomaterials have been widely used in many other fields, such as drug delivery, cancer therapy, and as nanoprobes in bioimaging. Thus, the preparation methods of calcium phosphate nanomaterials were systematically reviewed, and the multifunction strategies of calcium phosphate-based biomaterials have also been comprehensively summarized. Finally, the applications and perspectives of functionalized calcium phosphate biomaterials in bone tissue engineering, including bone defect repair, bone regeneration, and drug delivery, were illustrated and discussed by presenting typical examples.

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

Incidence and mortality of thyroid cancer in China, 2008-2012.

OBJECTIVE: To analyze the incidence and mortality rates of thyroid cancer (TC) in China from 2008 to 2012. METHODS: Incident and death cases of TC were retrieved from the National Central Cancer Registry (NCCR) database collecting from 135 cancer registries in China during 2008-2012. The crude incidence and mortality rates of TC were calculated by area (urban/rural), region (eastern, middle, western), gender and age group (0, 1-4, 5-9, …, 85+). China census in 2000 and world Segi's population were applied for age-standardized rates. Joinpoint (Version 4.6.0.0) model was used for time-trend analysis. RESULTS: The crude incidence rate of TC was 7.56/100,000 which ranked the seventh in overall cancers. The age-standardized incidence rates by China population (ASIRC) and by World population (ASIRW) were 6.25/100,000 and 5.52/100,000, respectively. The crude mortality of TC in China was 0.52/100,000. The age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.34/100,000 and 0.32/100,000, respectively. Incidence and mortality rates of TC were higher in females than in males and higher in urban areas than in rural areas. Eastern areas had the highest incidence followed by middle and western areas. TC incidence increased dramatically after age of 15 years, then peaked at 14.08/100,000 in the group of 50-54 years and finally decreased sharply after 55 years old. TC mortality increased with age in population, reaching the peak of 5.09/100,000 in sub-population aged 85 years or older. TC incidence increased by 4.73 times from 2.40/100,000 in 2003 to 13.75/100,000 in 2012 with an average annual increase of 20%, while TC mortality only increased slightly around 0.32/100,000 from 0.26/100,000 to 0.36/100,000. CONCLUSIONS: Appropriate targeted prevention, early detection and treatment programs can be carried out to curb the rapid growth trend of TC and control the disease burden.

Thyroid cancer: trends in incidence, mortality and clinical-pathological patterns in Zhejiang Province, Southeast China.

BACKGROUND: Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province. METHODS: Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012. The incidence and mortality rates were age-standardized to Segi's world population. A Joinpoint model was used to examine secular trends in age-adjusted thyroid cancer rates with the Joinpoint Regression Program Version 4.0.0. Thyroid cancer patients were recruited from Zhejiang Cancer Hospital from 1972 to 2014. Patient demographics, tumor histology and tumor size were compared among the different periods of 1972-1985, 1986-1999 and 2000-2014. RESULTS: The age-standardized incidence rate of thyroid cancer in Zhejiang cancer registries was 2.75/105 in 2000, and increased to 19.42/105 in 2012. Additionally, we observed significantly increasing incidence rates with the Annual Percent Change (APC) of 22.86% (95%CI, 19.2%-26.7%). The age-standardized mortality of thyroid cancer in Zhejiang cancer registries was 0.23/105 in 2000 and 0.25/105 in 2012. No significant change in mortality rate was found. We observed a rapid increase in the proportions of papillary thyroid carcinoma (PTC) in 12,508 patients with thyroid carcinoma identified in the Zhejiang Cancer Hospital from 1972 to 2014 while the proportions of poorly differentiated thyroid cancer (PDTC), medullary thyroid carcinoma (MTC) and follicular thyroid carcinoma (FTC) decreased over the decades. In the PTC cases, the proportion of patients with maximum tumor diameter (MTD) < 1 cm dramatically and significantly increased from 0 in 1972-1985 to 32.1% in 2000-2014. CONCLUSIONS: A rapid increase in incidence and a stable trend in mortality of thyroid cancer were found in the distribution of thyroid cancer. Most of the increased incidence was PTC, especially the papillary thyroid microcarcinoma (PTMC) with MTD < 1 cm. This increase in incidence might be due to increased diagnosis with advanced technology.

Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.

Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.

Uric Acid Promotes Osteogenic Differentiation and Inhibits Adipogenic Differentiation of Human Bone Mesenchymal Stem Cells.

To investigate the effect of uric acid on the osteogenic and adipogenic differentiation of human bone mesenchymal stem cells (hBMSCs). The hBMSCs were isolated from bone marrow of six healthy donors. Cell morphology was observed by microscopy and cell surface markers (CD44 and CD34) of hBMSCs were analyzed by immunofluorescence. Cell morphology and immunofluorescence analysis showed that hBMSCs were successfully isolated from bone marrow. The number of hBMSCs in uric acid groups was higher than that in the control group on day 3, 4, and 5. Alizarin red staining showed that number of calcium nodules in uric acid groups was more than that of the control group. Oil red-O staining showed that the number of red fat vacuoles decreased with the increased concentration of uric acid. In summary, uric acid could promote the proliferation and osteogenic differentiation of hBMSCs while inhibit adipogenic differentiation of hBMSCs.

[Crypotanshione reduces the expression of metadherin in DU145 prostate cancer cells].

OBJECTIVE: To investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells. METHODS: We treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p-AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours. RESULTS: CPT significantly inhibited the proliferation of the DU145 cells in a dose- and time-dependent manner (P < 0.05). After treatment with 10 µmol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 ± 4.51), (55.07 ± 5.67) and (70.84 ± 4.66)%, respectively, significantly higher than (3.1 ± 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 µmol/L CPT for 48 hours (P < 0.05). CONCLUSION: CPT can inhibit the proliferation and induce the apoptosis of DU145 prostate cancer cells, which may be associated with its suppression of the downstream PI3K/AKT signaling pathway by reducing the expression of metadherin in the DU145 cells.

Incidence and mortality of laryngeal cancer in China, 2011.

OBJECTIVE: Laryngeal cancer is the common cancer of the upper aerodigestive tract. We aimed to use the national cancer registration data in 2011 to estimate the incidence and mortality of laryngeal cancer within China. METHODS: Comparable, high-quality data from 177 population-based cancer registries were qualified for analysis. The pooled data were stratified by area, sex and age group. National new cases and deaths of laryngeal cancer were estimated using age-specific rates and national population in 2010. All incidence and death rates were age-standardized to the 2000 Chinese standard population and Segi's population, which were expressed per 100,000 populations. RESULTS: All 177 cancer registries covered a total of 175,310,169 population (98,341,507 in urban and 76,968,662 in rural areas), accounting for 13.01% of the national population. The data quality indicators of proportion of morphological verification (MV%), percentage of cancer cases identified with death certification only (DCO%) and mortality to incidence ratio (M/I) were 77.98%, 2.62% and 0.55, respectively. Estimated 20,875 new cases of laryngeal cancer were diagnosed and 11,488 deaths from laryngeal cancer occurred in China in 2011. The crude incidence rate of laryngeal cancer was 1.55/100,000 (2.69/100,000 in males and 0.35/100,000 in females). Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 1.13/100,000 and 1.14/100,000, respectively. Laryngeal cancer is much rarer in females than in males. The incidence rate was higher in urban areas than that in rural areas. The crude mortality rate of laryngeal cancer was 0.85/100,000 (1.42/100,000 in males and 0.25/100,000 in females). Age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were both 0.61/100,000. The mortality rate in males was much higher than that in females. There was no definite difference in mortality rates of laryngeal cancer between urban and rural areas. CONCLUSIONS: Larynx is a specialized area and cancer of larynx significantly affects the quality of life for the patients. Comprehensive measures should be carried out to prevent the ascent of laryngeal cancer.

TGFBR1 tagging SNPs and gastric cancer susceptibility: a two-stage case-control study in Chinese population.

The transforming growth factor (TGF)-ß is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF-ß receptor type I (TGFßR1) may be a modifier of cancer risk by constitutively decreasing the TGF-ß inhibitory signals during early tumorigenesis and increasing the TGF-ß signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two-stage case-control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P = 3.35 × 10(-3) for rs6478974 AT vs. TT and P = 0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P = 0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14-1.63 for rs6478974 AT/AA vs. TT; adjusted OR = 1.26, 95% CI: 1.05-1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR = 1.23, 95% CI: 1.08-1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han-Chinese population.

Association between cyclooxygenase-2 gene polymorphisms and head and neck squamous cell carcinoma risk.

Cyclooxygenase-2 (COX-2) is an inducible enzyme that catalyzes prostaglandins through inflammatory response, which may be involved in autoimmune diseases and cancer pathogenesis. Two potentially functional genetic single-nucleotide polymorphisms (COX-2 -1195G>A and 8473T>C) were supposed to contribute to head and neck squamous cell carcinoma (HNSCC) susceptibility. The aim of this study was to determine the association of these polymorphisms with HNSCC susceptibility in a Chinese Han population. In this study, 2 SNPs were genotyped by TaqMan methods in a patient-control study including 260 patients with HNSCC and 1047 cancer-free controls in a Chinese Han population. We found significant difference in the frequency of alcohol consumption between the patients with HNSCC and controls (P < 0.001), but the genotype frequencies of the 2 polymorphisms were not significantly different between the patients and controls. Further stratified analysis indicated that none of the genotypes were associated with increased risk for HNSCC. This research indicated that the COX-2 -1195G>A and 8473T>C polymorphisms may not be involved in the development of HNSCC in the Chinese Han population. However, further perspective studies are warranted to test these findings and further investigate the potential interactions involving the COX-2 polymorphism and HNSCC.

[Analysis of cervical cancer incidence and mortality in cancer registries of Zhejiang province, 2000 to 2009].

OBJECTIVE: To investigate the cervical cancer incidence and mortality in cancer registries of Zhejiang province during 2000 to 2009. METHODS: The data of cervical cancer incidence and mortality were collected from six cancer registries in Zhejiang province. Staff of Zhejiang Provincial Cancer Prevention and Control Office checked, sorted and analyzed the data to calculate crude, standardized rate and trend. Chinese census in 1982 and Segi's population were used for age-standardized incidence and mortality rates. RESULTS: The incidence rate of cervical cancer in Zhejiang cancer registration areas was 11.78/100 000 during 2000 to 2009, and age-standardized incidence rates by Chinese standard population and by world standard population were 7.05/100 000 and 8.62/100 000, respectively. The mortality rate was 1.89/100 000, and age-standardized mortality rates by Chinese standard population and by world standard population were 0.95/100 000 and 1.23/100 000, respectively. The age-specific incidence rates showed different trends, increased significantly after the age of 25, peaked at 45-year-old group, which was 23.03/100 000 (578/2 510 099) , and decreased at the age of 50, while the age-specific mortality rates gentlely increased, peaked at 85 years of age group, which was 11.94/100 000 (33/276 414) . The cervical Cancer Incidence from 5.96/100 000 (86/1 443 589) in 2000, increased to 18.90/100 000 (898/4 751 426) in 2009, the annual percent change (APC) was 16.64% (95%CI:11.87%-21.61%). The mortality showed a gentle upward trend from 1.45/100 000 (21/1 443 589) , increased to 2.53/100 000 (120/4 751 426) in 2009, the APC was 6.63% (95%CI:1.73%-11.77%). CONCLUSION: Cervical cancer showed younger trend, the incidence and mortality trends showed an increasing trend, should strengthen the prevention and control of cervical cancer.

Effectiveness of Risk-Adapted Upper Gastrointestinal Cancer Screening in China: Prospective Cohort Study.

Background: Previous studies have proved the effectiveness of endoscopic screening in rural areas; however, long-term, high-quality evidence regarding the effectiveness of risk-adapted upper gastrointestinal cancer (UGC) sequential screening strategies in resource-rich regions is currently lacking. Objective: The objectives were to validate the effectiveness of risk-adapted sequential screening strategies in UGC prevention and control and assess the potential of sequential screening to lower mortality rates. Methods: Based on the Cancer Screening Program in Urban China, a prospective, large-scale cohort study based on population was conducted to recruit individuals from 4 cities in China from 2013-2019. Those identified as having a high risk of UGC according to a validated risk-score model were advised to undergo endoscopy tests. Follow-up outcomes were tracked until June 2021. Incidence of UGC, UGC-related mortality, and all-cause mortality were evaluated between the screened and nonscreened cohorts. Results: The study included 153,079 participants at baseline. In total, 113,916 (74.42%) of the participants were designated as low risk of UGC. The remaining 39,163 (25.68%) participants were deemed to be at high risk of UGC and were offered gastroscopy tests. Among the high-risk participants, 9627 (compliance rate 24.6%) adhered to the gastroscopy tests. Over a median follow-up of 6.05 (IQR 3.06-7.06) years, 622 UGC cases, 180 UGC deaths, and 1958 all-cause death cases were traced. The screened cohort exhibited the highest cumulative incidence of UGC (119.2 per 100,000 person-years), followed by the nonscreened and low-risk cohorts. Obvious reductions in both all-cause mortality and UGC mortality were observed between those who undertook screening (153.7 and 4.7 per 100,000 person-years, respectively) and the nonscreened group (245.3 and 27 per 100,000 person-years, respectively). The screening population showed a significant 36% and 82% reduction in both all-cause mortality (hazard ratio [HR] 0.64, 95% CI 0.49-0.83, P<.001) and UGC mortality (HR 0.18, 95% CI 0.04-0.74, P=.02), respectively, compared to the nonscreened group. Reductions of 35% in all-cause mortality (HR 0.65, 95% CI 0.49-0.86, P=.003) and 81% in UGC mortality (HR 0.19, 95% CI 0.05-0.80, P=.02) were observed in participants aged older than 55 years in the screened group compared to the nonscreened group. The reductions in all-cause mortality and UGC mortality were statistically significant in males (all-cause mortality: HR 0.64, 95% CI 0.47-0.88, P=.005; UGC mortality: HR 0.10, 95% CI 0.01-0.72, P=.02), but significant reductions were not observed in females (all P values were >.05). Conclusions: Our study suggests the significance of one-off risk-adapted UGC screening in reducing both all-cause mortality and UGC mortality, particularly among high-risk individuals, indicating its effectiveness in UGC prevention and management.

Cancer survival analysis on population-based cancer registry data in Zhejiang Province, China (2018-2019).

Objective: This is a comprehensive overview of long-term cancer survival in Zhejiang Province, China. Hybrid analysis, a combination of cohort and period analysis, has been proposed to derive up-to-date cancer survival estimates. Using this approach, we aimed to timely and accurately analyze the 5-year relative survival (RS) and net survival (NS) in cancer registries of Zhejiang Province, China. Methods: A total of 255,725 new cancer cases diagnosed during 2013-2017 were included in 14 cancer registries in Zhejiang Province, China, with a follow-up on vital status until the end of 2019. The hybrid analysis was used to calculate the 5-year RS and 5-year NS during 2018-2019 for overall and stratifications by sex, cancer type, region, and age at diagnosis. Results: During 2018-2019, the age-standardized 5-year RS and NS for overall cancer in Zhejiang was 47.5% and 48.6%, respectively. The age-standardized 5-year RS for cancers of women (55.4%) was higher than that of men (40.0%), and the rate of urban areas (49.7%) was higher than that of rural areas (43.1%). The 5-year RS declined along with age, from 84.4% for ages <45 years to 23.7% for ages >74 years. Our results of the RS and NS showed the similar trend and no significant difference. The top five cancers with top age-standardized 5-year RS were thyroid cancer (96.0%), breast cancer (84.3%), testicular cancer (79.9%), prostate cancer (77.2%), and bladder cancer (70.6%), and the five cancers with the lowest age-standardized 5-year RS were pancreatic cancer (6.0%), liver cancer (15.6%), gallbladder cancer (17.1%), esophageal cancer (22.7%), and leukemia (31.0%). Conclusions: We reported the most up-to-date 5-year cancer RS and NS in Zhejiang Province, China for the first time, and found that the 5-year survival for cancer patients in Zhejiang during 2018-2019 was relatively high. The population-based cancer registries are recognized as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems.

Type 2 diabetes, glycaemic traits and upper gastrointestinal cancer risk: a prospective cohort study.

BACKGROUND: Type 2 diabetes (T2D) has been linked with site-specific upper gastrointestinal (UGI) cancers during the past decades, but associations are still inconclusive. This study aimed to determine the association between T2D, glycaemic traits (random blood glucose and HbA1c) and UGI cancer (oesophageal and gastric cancer). METHODS: In the present study, based on the large-scale prospective cohort of UK Biobank, we included 452 631 eligible participants. T2D was defined according to baseline self-report data, clinical data and biochemistry data. Random blood glucose and HbA1c were measured at baseline. Polygenic risk score was used to classify individuals into different UGI cancer genetic risks. Multivariable Cox regression models were used to estimate HRs and 95% CIs. RESULTS: During a median follow-up of 10.26 years (IQR: 9.47-10.97), 1392 incident UGI cancer cases were identified. T2D was significantly associated with a 44% increment in UGI cancer risk (95% CI 1.22 to 1.70, p<0.001). Moreover, per SD increase in random blood glucose and HbA1c was associated with 7% (95% CI 1.03 to 1.12, p<0.001) and 6% (95% CI 1.04 to 1.09, p<0.001) increased hazards of developing UGI cancer, respectively. Patients with T2D at high genetic risk had a 2.33-fold hazard of UGI cancer (95% CI 1.66 to 3.28, p<0.001), compared with non-T2D individuals at low genetic risk. CONCLUSION: Our results indicate that T2D and elevated levels of glycaemic traits may be risk factors for incident UGI cancer. Individuals with a high genetic risk and T2D have a significantly increased risk of developing UGI cancer.

Construction and evaluation of a polygenic hazard score for prognostic assessment in localized gastric cancer.

To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer (GC), we performed two genome-wide association studies (GWASs) of GC survival in the Jiangsu (N = 1049) and Shanghai (N = 1405) cohorts. By using a TCGA dataset, we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated loci. Then, we constructed a weighted polygenic hazard score (PHS) and developed a nomogram in combination with clinical variables. We also evaluated prognostic accuracy with the time-dependent receiver operating characteristic (ROC) curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). We identified a single nucleotide polymorphism (SNP) of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12 × 10-8, and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA cohort. The PHS derived from these 26 SNPs (PHS-26) was an independent prognostic factor for GC survival (all P < 0.001). The 5-year AUC of PHS-26 was 0.68, 0.66 and 0.67 for Jiangsu, Shanghai and their pooled cohorts, respectively, which increased to 0.80, 0.82 and 0.81, correspondingly, after being integrated into a nomogram together with variables of the clinical model. The PHS-26 could improve the NRIs by 16.20%, 4.90% and 8.70%, respectively, and the IDIs by 11.90%, 8.00% and 9.70%, respectively. The 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.

Nonsynonymous polymorphisms in FAT4 gene are associated with the risk of esophageal cancer in an Eastern Chinese population.

FAT4 plays a crucial role in carcinogenesis as a key component of the Hippo signaling pathway. We hypothesized that potential functional polymorphisms in the FAT4 gene may modify the risk of esophageal cancer. To test this hypothesis, we evaluated the association between four nonsynonymous polymorphisms (rs1039808, rs12508222, rs1567047 and rs1014867) in FAT4 and esophageal cancer risk in a case-control study of 2,139 esophageal cancer cases and 2,273 controls in a Chinese population. We found that the T allele of rs1014867 (Pro4972Ser) was significantly associated with a decreased risk of esophageal cancer (odds ratio [OR]=0.77, 95% confidence interval [95% CI]=0.66-0.90; p=1.42 × 10(-3)). We also observed a borderline significant association between rs1039808 (Ala807Val) and esophageal cancer risk (OR=0.90, 95% CI=0.82-1.00; p=0.050), which was more prominent in non-drinkers (OR=0.82, 95% CI=0.71-0.94; p=6.53 × 10(-3)). Furthermore, we detected a significant interaction between rs1039808 genotypes and alcohol drinking on esophageal cancer risk (p=0.013). These findings indicate that the nonsynonymous variants rs1014867 (Pro4972Ser) and rs1039808 (Ala807Val) of FAT4 may contribute to esophageal cancer susceptibility.

Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese.

BACKGROUND: Genome-wide association study (GWAS) has identified that rs8050136 C/A polymorphism in fat mass and obesity-associated gene (FTO) was associated with the risk of type 2 diabetes (T2D) in Europeans. But this association was abolished after adjustment for body mass index (BMI), suggesting that the effect of rs8050136 on T2D risk might be mediated by BMI in Europeans. However, the findings in subsequent studies were inconsistent among Asian populations. To determine whether rs8050136 polymorphism in FTO is independently associated with the risk of T2D in Chinese, we conducted a case-control study with 2,925 T2D patients and 3,281 controls in Han Chinese. RESULTS: Logistic regression revealed that the A allele of rs8050136 was significantly associated with an increased risk of T2D, independent of BMI (odds ratio (OR) = 1.17, 95% confidence interval (95% CI) = 1.03-1.32, p = 0.016). Meta-analysis containing 10 reported studies and our data with a total of 15,819 cases and 18,314 controls further confirmed the association between rs8050136 polymorphism and T2D risk in East Asians (OR = 1.13, 95% CI = 1.07-1.19). CONCLUSIONS: Our findings indicate that the genetic variant in FTO may contribute to T2D risk in Han Chinese and rs8050136 polymorphism may be a genetic marker for T2D susceptibility.

[Incidence and mortality of cancer in Zhejiang province in 2009].

OBJECTIVE: To investigate the incidence and mortality of cancer registered in Zhejiang province in 2009. METHODS: The statistics of incidence and mortality of cancer were collected from 6 population-based cancer registries in Zhejiang province, including 30 613 new incidence cases and 16 920 death cases reported in 2009. The 6 cancer registries covered population at 9 560 699 in all. The crude rate, age-standardized rate, cumulative rate (0-74 years old), cut rate (35-64 years old), age-specific rate of incidence/mortality as well as the constitution of top 10 common cancers were then calculated and analyzed. The age-standardized rate was calculated and adjusted by the Chinese standard population in 1982 as well as the Segi's world standard population. RESULTS: The crude incidence of cancer was 320.20/100 000. Age-standardized incidence by Chinese standard population and by world standard population were separately 161.99/100 000 and 207.92/100 000, the cumulative rate was 23.83% and the cut rate was 346.87/100 000. Meanwhile, the crude mortality rate was 176.97/100 000, and the age-standardized mortality by Chinese standard population and by world standard population were 79.17/100 000, 107.02/100 000, respectively; and the cumulative mortality rate was 12.23% and cut rate was 139.75/100 000. Age-specific incidence among 0-34 years old population remained low; however, the incidence among 35-39 age group increased obviously (116.46/100 000, 954 cases). The incidence among 45-49 age group elevated even more sharply (272.97/100 000, 2388 cases) and finally reached the peak among 80-84 age group (1564.36/100 000, 2272 cases). Age-specific mortality arose among 40-44 age group (48.06/100 000, 424 cases) and reached its peak among 80-84 age group (1392.23/100 000, 2022 cases) as well. The most common types of cancer were lung cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, esophageal cancer, thyroid cancer, pancreatic cancer, cervical cancer and lymphoma, which accounted for 74.37% (22 763/30 613) of all new cancer cases.Lung cancer, liver cancer, gastric cancer, colorectal cancer, esophageal cancer, pancreatic cancer, leukemia, lymphoma, brain tumors and breast cancer accounted for 87.75% (14 848/16 920) of all cancer deaths. CONCLUSION: The incidence and mortality of cancer both increased in 2009 according to the statistics from cancer registry in Zhejiang province.Lung cancer, malignant tumor in digestive system and breast cancer were still the key challenges in cancer prevention and control. Meanwhile, the increased incidence of thyroid cancer should also be noticed.

Disparity in Lung Cancer Screening Among Smokers and Nonsmokers in China: Prospective Cohort Study.

BACKGROUND: Low-dose computed tomography (LDCT) screening is effective in reducing lung cancer mortality in smokers; however, the evidence in nonsmokers is scarce. OBJECTIVE: This study aimed to evaluate the participant rate and effectiveness of one-off LDCT screening for lung cancer among smokers and nonsmokers. METHODS: A population-based prospective cohort study was performed to enroll participants aged between 40 and 74 years from 2013 to 2019 from 4 cities in Zhejiang Province, China. Participants who were evaluated as having a high risk of lung cancer from an established risk score model were recommended to undergo LDCT screening. Follow-up outcomes were retrieved on June 30, 2020. The uptake rate of LDCT screening for evaluated high-risk participants and the detection rate of early-stage lung cancer (stage 0-I) were calculated. The lung cancer incidence, lung cancer mortality, and all-cause mortality were compared between the screened and nonscreened groups. RESULTS: At baseline, 62.56% (18,818/30,079) of smokers and 6% (5483/91,455) of nonsmokers were identified as high risk (P<.001), of whom 41.9% (7885/18,818) and 66.31% (3636/5483) underwent LDCT screening (P<.001), respectively. After a median follow-up of 5.1 years, 1100 lung cancer cases and 456 all-cause death cases (116 lung cancer death cases) were traced. The proportion of early-stage lung cancer among smokers was 60.3% (173/287), which was lower than the proportion of 80.3% (476/593) among nonsmokers (P<.001). Among smokers, a higher proportion was found in the screened group (72/106, 67.9%) than the nonscreened group (56/114, 49.1%; P=.005), whereas no significance was found (42/44, 96% vs 10/12, 83%; P=.20) among nonsmokers. Compared with participants who were not screened, LDCT screening in smokers significantly increased lung cancer incidence (hazard ratio [HR] 1.39, 95% CI 1.09-1.76; P=.007) but reduced lung cancer mortality (HR 0.52, 95% CI 0.28-0.96; P=.04) and all-cause mortality (HR 0.47, 95% CI 0.32-0.69; P<.001). Among nonsmokers, no significant results were found for lung cancer incidence (P=.06), all-cause mortality (P=.89), and lung cancer mortality (P=.17). CONCLUSIONS: LDCT screening effectively reduces lung cancer and all-cause mortality among high-risk smokers. Further efforts to define high-risk populations and explore adequate lung cancer screening modalities for nonsmokers are needed.