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In prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-β1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-β1/SMAD signaling pathway.

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. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC) often occurs in the elderly, and approximately 40% of patients are 70 years or older. To investigate the long‐term survival of EC in elderly patients, to provide a theoretical direction for better management and predicting survival of EC based on the hospital‐based multi‐center study in China. Methods: The study was conducted in 18 hospitals including 6 provincial hospitals, 8 municipal hospitals, and 4 county hospitals. We extracted information from medical record homepage, records of admission and discharge, and pathological diagnosis reports from the medical record department of the elderly patients at 70–84 years old to obtain the 3‐year and 5‐year overall survival (OS), and main associated factors, and to analyze the current therapeutic effect of different treatment options for elderly patients. Results: The 3‐year and 5‐year OS rate of the 1013 elderly patients was 44.8% and 32.8%, respectively. Their median survival was 28.00 months. The median survival of patients with squamous cell carcinoma was longer than that of other pathological type (squamous vs. other types: 31.00 vs. 20.00 months, p = 0.018). The median survival of patients with surgery only or combined therapy was longer than that of radiotherapy, chemotherapy, and no therapy (surgery only vs. combined therapy vs. radiotherapy vs. chemotherapy vs. no therapy: 56.00 vs. 33.00 vs. 26.00 vs.18.00 vs. 16.00 months, p < 0.001). The 5‐year OS rate of patients with highly differentiated cancer was higher than that of medium differentiated and poor differentiation/undifferentiated. In multivariate analysis, the older ages, pathological stage, were independent prognostic risk factors for poor EC survival. Treatment method was independent protective factors predictive of a good EC OS. Conclusions: The survival rate of the elderly EC patients was still low in China. Age, therapy method, and pathological stage were mainly associated with the survival rate of EC in elderly patients. [ABSTRACT FROM AUTHOR]

Objective: Using data from cancer registries to estimate thyroid cancer incidence and mortality in China, 2015. Methods: Data submitted from local cancer registries were checked and evaluated according to the criteria of data quality control, a total of 368 cancer registries' data were qualified for the final analysis. Data were stratified by area (urban/rural, eastern/central/western), sex and age, combined with national population data to estimate thyroid cancer incidence and mortality in China, 2015. Results: Approximately 200,700 new cases were diagnosed in 2015, accounting for 5.11% of all cancer cases. The crude incidence rate was 14.60/100,000. Age-standardized incidence rates by Chinese standard population (ASIRC) and world standard population (ASIRW) were 12.05/100,000 and 10.44/100,000, with the cumulative incidence rate (0–74 years old) of 1.00%. About 7,900 deaths of thyroid cancer were reported in 2015, accounting for 0.34% of all cancer deaths. The crude mortality rate was 0.58/100,000, age-standardized mortality rates by Chinese standard population (ASMRC) and world standard population (ASMRW) were 0.37/100,000 and 0.36/100,000. The age-standardized incidence and mortality in females were significantly higher than those in males (P < 0.001). The rates in urban areas were higher than those in rural areas (P < 0.001). The ASIRC in eastern areas was higher than that in central and western areas (P < 0.001), while the ASMRC in central areas was higher than that in eastern and western areas (P < 0.001). Conclusions: The burden of thyroid cancer was heavy in China, cancer control faces the problem of the disparity between geographic areas, and the incidence and mortality rates were varied by sex and age. Targeted cancer preventive measures should be put into practice. [ABSTRACT FROM AUTHOR]

Background: We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health‐related quality of life (HRQoL). Methods: A hospital‐based multicenter cross‐sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life‐5 dimension (EQ‐5D‐3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ‐5D utility scores. Results: A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self‐reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ‐5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ‐5D utility scores of EC patients. Conclusions: There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost‐utility analysis in populations in China. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer is the one of the most prevalent cancer of the upper respiratory tract. Aiming to get a better understanding of the epidemiological characteristics and trends of laryngeal cancer in Zhejiang cancer registry in China during 2000-2011, we used the standardized quality control and statistical methods to analyze the incidence and mortality that were vital for making decision about laryngeal cancer prevention and control.Materials and Methods: Comparably high-quality data from eight population-based cancer registries in Zhejiang from 2000 to 2011 were qualified for analysis. The pooled data were stratified by area, sex, and age group. All incidence and mortality rates were age-standardized to the 2000 Chinese standard population and Segi's population, which were expressed per 100,000 populations. Average annual percent changes (AAPCs) and 95% confidence intervals of laryngeal cancer incidence and mortality were calculated for the temporal trends. The logarithmic trend line was also drawn to reflect the time trends of incidence and mortality.Results: During the 12 years, the 8 cancer registries covered a total of 81,758,277 person-year population (65,500,842 in urban and 16,257,435 in rural areas) including 41,315,911 person-year males and 40,442,366 person-year females. The age-standardized incidence rates were 1.10/10(5) by Chinese population and 1.12/10(5) by world population, respectively. The incidence of laryngeal cancer was relatively low in subjects under 44 years old. Then, it increased sharply after 45 years old and finally reached the peak in subjects of 75-79 years old. The age-standardized mortality rates of the Chinese population and world population were 0.28/10(5) and 0.35/10(5), respectively. The mortality of laryngeal cancer was at a low level in subjects under 49 years old. The rate dramatically increased in subjects over 50 years old, and then peaked in the age group of 80-84 years. The crude incidence of laryngeal cancer in Zhejiang cancer registration areas in 2000 was approximately 1.39/10(5), and it reached 1.78/10(5) in 2011, with the AAPC of 2.47%; the temporal trend line indicates that the incidence remained steady during the 12 years. The crude mortality of laryngeal cancer in Zhejiang registration areas in 2000 was about 0.30/10(5) and increased to 0.66/10(5), with the AAPC of 4.24% which showed no statistical significance; the temporal trend line indicates that mortality was going up to a certain extent, but not evident.Conclusions: Laryngeal cancer significantly influenced the quality of life for the patients. The comprehensive measures should be carried out to prevent the upward trend of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We have previously confirmed the associations of genetic variants in HHEX, CDKAL1, VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes in Han Chinese are largely unknown. Methodology/Principal Findings: We conducted a two-stage case-control study consisting of 2,925 cases and 3,281controls to examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio (OR) = 1.41, P = 9.91 × 10–16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34 × 10–10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 × 10-4 for rs1552224) and SLC30A8 (OR = 1.19, P = 1.43 × 10-5 for rs13266634). We further evaluated the cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or more risk alleles had a nearly 4-fold increased risk for developing type 2 diabetes compared with those carrying less than 6 risk alleles [adjusted OR = 3.68, 95% confidence interval (CI): 2.76–4.91]. Adding the genetic factors to clinical factors slightly improved the prediction of type 2 diabetes, with the area under the receiver operating characteristic curve increasing from 0.76 to 0.78. However, the difference was statistically significant (P < 0.0001). Conclusions/Significance: We confirmed associations of SNPs in KCNQ1, CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The utilization of genetic information may improve the accuracy of risk prediction in combination with clinical characteristics for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer (PCa) as competitive endogenous RNA. The present study aimed to investigate the molecular mechanisms of lncRNA small nucleolar RNA host gene 16 (SNHG16) in the proliferation and metastasis of PCa cells. Cancer tissues and adjacent normal tissues were collected from 80 patients with PCa who did not receive any treatment. Reverse transcription-quantitative PCR analysis was performed to detect the expression levels of SNHG16, hsa-microRNA (miRNA/miR)-373-3p and transforming growth factor-β receptor type 2 (TGF-β-R2), and Spearman's correlation coefficient analysis was performed to assess the correlations between these molecules. Furthermore, the effects of SNHG16 knockdown and overexpression on the biological functions of DU-145 PCa cells and TGF-β-R2/SMAD signaling were analyzed. The dual-luciferase reporter assay was performed to assess the associations between SNHG16 and miR-373-3p, and TGF-β-R2 and miR-373-3p, the effects of which were verified via rescue experiments. The results demonstrated that the expression levels of SNHG16 and TGF-β-R2 were significantly upregulated in PCa tissues, whereas miR-373-3p expression was significantly downregulated (P<0.001). In addition, negative correlations were observed between SNHG16 and miR-373-3p (rho, −0.631) and miR-373-3p and TGF-β-R2 (rho, −0.516). Overexpression of SNHG16 significantly promoted the proliferation, migration and invasion of PCa cells (P<0.05), and significantly increased the protein expression levels of TGF-β-R2, phosphorylated (p)-SMAD2, p-SMAD3, c-Myc and E2F4 (P<0.001). Notably, the results revealed that miR-373-3p is a target of SNHG16, and miR-373-3p knockdown rescued short hairpin (sh)-SNHG16-suppressed cellular functions by promoting TGF-β-R2/SMAD signaling. The results also revealed that miR-373-3p targets TGF-β-R2. Notably, transfection with miR-373-3p inhibitor rescued sh-TGF-β-R2-suppressed cell proliferation and migration. Taken together, the results of the present study suggest that SNHG16 promotes the proliferation and migration of PCa cells by targeting the miR-373-3p/TGF-β-R2/SMAD axis. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 (COX-2) involves in multiple processes in carcinogenesis, including inflammation, apoptosis inhibition, immune response suppression, tumor cell invasion, and angiogenesis. COX-2 is overexpressed in various cancers, including gastric cancer. COX-2 is encoded by prostaglandin endoperoxide synthase 2 ( PTGS2) gene. We hypothesized that potentially functional polymorphisms in PTGS2 may contribute to gastric cancer risk. To assess this hypothesis, we conducted a case-control study with 1681 gastric cancer cases and 1916 control subjects in a Chinese population to evaluate the association between a polymorphism in 3′-untranslated region of PTGS2, rs5275, and the risk of gastric cancer. Logistic regression analysis revealed that variant allele (C) of rs5275 was significantly associated with an increased risk of gastric cancer (per allele odds ratio [OR]=1.14, 95% confidence interval [CI]=1.01-1.29, p=0.030). This association was more prominent in females (per allele OR=1.42, 95% CI=1.11-1.81, p=0.005) and nonsmokers (per allele OR=1.35, 95% CI=1.14-1.59, p=0.001). Interestingly, we detected a negative interaction between rs5275 and smoking on the gastric cancer risk ( p=0.007). Our findings indicate that PTGS2 rs5275T/C may be a candidate genetic marker for gastric cancer susceptibility. [ABSTRACT FROM AUTHOR]

A single nucleotide polymorphism (SNP) rs999737 at 14q24.1 was identified as a susceptibility marker of breast cancer in a genome-wide association study of the European population, which was also confirmed by some of the following studies in populations of European descent. However, rs999737 is very rare or nonpolymorphic in non-Europeans including Chinese, and the role of other genetic variants at 14q24.1 has not been evaluated in populations of non-European descent. In this study, we first selected 21 common tagging SNPs (minor allele frequency [MAF] >0.05 in the Chinese population) by searching the Hapmap database, covering a linage disequilibrium region of more than 70 Kb at 14q24.1, and then conducted a two-stage study (stage I: 878 cases and 900 controls; stage II: 914 cases and 967 controls) to investigate the associations between these tagging SNPs and risk of breast cancer in a Chinese population. In stage I, two SNPs (rs2842346 and rs17828907) were identified to be significantly associated with breast cancer risk ( p=0.030 and 0.027 for genotype distributions, respectively). However, no significant associations were found between these two SNPs and breast cancer risk in either stage II or the combined dataset. These findings suggest that common variants at 14q24.1 might not be associated with the risk of breast cancer in the Chinese population, which will need the replication in additional larger studies. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) on chromosome 6p21.1 and 6p22.3 as type 2 diabetes (T2D) susceptibility loci in the European and Japanese populations. However, these SNPs have not been well evaluated in Chinese population. Here, we performed a case-control study with 2925 T2D cases and 3281 controls in a Chinese population. We used TaqMan OpenArray and Sequenom MassARRAY to genotype the four SNPs (rs4712523, rs7756992, rs4712524 and rs6931514) in CDKAL1 (cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1) at 6p22.3 and one SNP (rs9472138) near vascular endothelial growth factor A (VEGFA) at 6p21.1. All the five SNPs were significantly associated with T2D risk with overall effects (odds ratio, OR) from 1.19 to 1.29 in the additive genetic model (rs6931514: OR=1.29, 95% confidence intervals (95% CI)=1.19-1.39, P=5.6 × 10−10; rs7756992: OR=1.23, 95% CI=1.15-1.32, P=1.2 × 10−8; rs4712523: OR=1.25, 95% CI=1.15-1.35, P=3.8 × 10−8; rs4712524: OR=1.24, 95% CI=1.15-1.35, P=6.8 × 10−8; rs9472138: OR=1.19, 95% CI=1.05-1.34, P=006). Conditional analysis identified two independent signals (rs6931514 at 6p22.3 and rs9472138 at 6p21.1) that were significantly associated with T2D. Compared with the wild homozygote of rs6931514 and rs9472138, subjects with variant alleles of the two SNPs had increased risk for T2D susceptibility in a dose-response manner (Ptrend=7.4 × 10−12). Our findings indicated that genetic variants of CDKAL1 and VEGFA on chromosome 6 may contribute to T2D risk in Chinese population, especially for rs9472138 at 6p21.1 identified for the first time to significantly increase the T2D risk in Chinese individuals. [ABSTRACT FROM AUTHOR]

Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility. Its pathophysiology is largely unknown, and few genetic influences have been defined. To identify common variants contributing to NOA in Han Chinese men, we performed a three-stage genome-wide association study of 2,927 individuals with NOA and 5,734 controls. The combined analyses identified significant (P < 5.0 × 10?8) associations between NOA risk and common variants near PRMT6 (rs12097821 at 1p13.3: odds ratio (OR) = 1.25, P = 5.7 × 10?10), PEX10 (rs2477686 at 1p36.32: OR = 1.39, P = 5.7 × 10?12) and SOX5 (rs10842262 at 12p12.1: OR = 1.23, P = 2.3 × 10?9). These findings implicate genetic variants at 1p13.3, 1p36.32 and 12p12.1 in the etiology of NOA in Han Chinese men. [ABSTRACT FROM AUTHOR]

Gastric cancer, including the cardia and non-cardia types, is the second leading cause of cancer-related deaths worldwide. To identify genetic risk variants for non-cardia gastric cancer, we performed a genome-wide association study in 3,279 individuals (1,006 with non-cardia gastric cancer and 2,273 controls) of Chinese descent. We replicated significant associations in an additional 6,897 subjects (3,288 with non-cardia gastric cancer and 3,609 controls). We identified two new susceptibility loci for non-cardia gastric cancer at 5p13.1 (rs13361707 in the region including PTGER4 and PRKAA1; odds ratio (OR) = 1.41; P = 7.6 × 10?29) and 3q13.31 (rs9841504 in ZBTB20; OR = 0.76; P = 1.7 × 10?9). Imputation analyses also confirmed previously reported associations of rs2294008 and rs2976392 on 8q24, rs4072037 on 1q22 and rs13042395 on 20p13 with non-cardia gastric cancer susceptibility in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Previous studies have reported that the expression levels of microRNA (miR)-28-3p are downregulated in prostate cancer (PCa) compared with those in adjacent normal tissues. However, to the best of our knowledge, the function and underlying mechanisms of miR-28-3p in PCa have not been reported. The present study aimed to explore the role of miR-28-3p and its mechanism in the development of PCa. In the present study, miR-28-3p and ADP-ribosylation factor 6 (ARF6) expression levels were analyzed using reverse transcription-quantitative PCR (RT-qPCR). Cell proliferation, colony formation, apoptosis, migration and invasion were determined using Cell Counting Kit-8, colony forming, flow cytometry and Transwell assays, respectively. The association between miR-28-3p and ARF6 was investigated using a dual luciferase reporter assay. ARF6, Rac1, Erk1/2 and phosphorylated (p)-Erk1/2 protein expression levels were analyzed using western blotting. The results of the present study revealed that miR-28-3p expression levels were downregulated, whereas ARF6 expression levels were upregulated in PCa cell lines (LNCaP, 22Rv-1, PC-3 and DU145) compared with those in the normal prostate line RWPE-1. The overexpression of miR-28-3p promoted cell apoptosis, and inhibited cell proliferation, colony formation, migration and invasion. However, the knockdown of miR-28-3p exerted the opposite results. The results of the dual luciferase reporter assays, RT-qPCR and western blotting indicated that ARF6 was a target gene of miR-28-3p. Finally, rescue experiments demonstrated that ARF6 overexpression attenuated the effects of the miR-28-3p mimic by upregulating Rac1 and p-Erk1/2 expression in PCa cells. In conclusion, these findings indicated that miR-28-3p may inhibit the biological behaviors of PCa cells by targeting ARF6, and therefore may represent a novel therapeutic candidate for PCa. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions Plain Language Summary 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.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.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.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. 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. 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. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) in populations of European ancestry have identified nine single nuclear polymorphisms (SNP) on chromosome 11 related to type 2 diabetes (T2D) susceptibility. Herein, we further evaluate the association of these SNPs and T2D in a Chinese Han population. We performed a case-control study of 2925 T2D cases and 3281 controls to evaluate the association of five SNPs of KCNJ11 , MTNR1B , CENTD2 and LOC387761 and T2D in addition to the previously reported four SNPs of KCNQ1 . Multiple logistic regression was used to evaluate SNP's effect by adjustment for confounding factor age, sex and BMI. In the first stage, SNPs rs1552224 at CENTD2 were significantly associated with T2D and the association was statistically significant in the whole study population (P = 0.001) although it was not replicated in the second stage. rs1552224 and rs2237897 of KCNQ1 showed significant joint effect on T2D and there was a significant decreased risk of T2D with the number increase of risk alleles (P for trend = 3.81 × 10 −17 ). Compared to those without carrying any risk allele, individuals carrying one, two, and three or four risk alleles had a 30.7%, 44.8% and 62.0% decreased risk for developing T2D, respectively. Our finding suggests that genetic variant rs1552224 of CENTD2 on chromosome 11 contributes to an independent effect as well as joint cumulative effect with rs2237897 of KCNQ1 on the risk of T2D in Chinese Han population, and further functional research would be warranted. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Chinese National Cancer Center. Published by Elsevier B.V.)

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., (©Le Wang, Youqing Wang, Fei Wang, Yumeng Gao, Zhimei Fang, Weiwei Gong, Huizhang Li, Chen Zhu, Yaoyao Chen, Lei Shi, Lingbin Du, Ni Li. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 14.03.2023.)

Background : Survival of patients with stage I non-small cell lung cancer (NSCLC) varies greatly. We sought to explore whether presence of oncogenic alterations in histologically-negative lymph nodes (LNs) can be of prognostic significance in stage I lung adenocarcinoma (LUAD). Methods : Genomic analysis of oncogenic alterations was applied to 123 stage I LUAD tumors. The same genomic variants identified in primary tumors were examined in corresponding histologically-negative LNs. Results : A total of 102 (82.9%) patients had at least one canonical oncogenic alteration detected in primary tumors, and 57 LNs from 12 patients (11.8%) were found to carry the identical oncogenic alterations detected in the corresponding primary tumor tissues, including EGFR mutations (six cases), KRAS mutations (three cases), ALK fusion (one case), BRAF mutation (one case) and HER2 & NRAS co-mutations (one case). None of these LNs was found to have occult tumor cells by routine pathological assessment or immunohistochemistry staining using antibodies against pan-cytokeratins (AE1/AE3) and the epithelial marker Ber-EP4. The detection rate of oncogenenic alterations in LN was significantly higher in RAS -mutant tumors than EGFR mutant tumors (36.36% verse 7.41%, p = 0.017). Patients with oncogenic alterations in LN showed inferior disease-free survival (DFS, p = 0.025) and overall survival (OS, p = 0.027). Furthermore, patients with RAS -mutations detected in LN had the worst DFS and OS ( p = 0.001). Among the 11 patients with RAS mutation in primary tumors, DFS and OS in the four patients with mutations detected in LN were significantly shorter than the remaining seven patients without mutations LN (DFS, p = 0.001, OS, p = 0.002). Conclusions : Genomic analysis has the potential to detect oncogenic alterations in regional LNs for localized LUAD and presence of oncogenic alterations in regional LN may be associated with inferior clinical outcome of stage I LUAD, particularly for certain molecular subgroups. ClinicalTrials.gov ID NCT04266691.

Importance: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed., Objective: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer., Design, Setting, and Participants: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021., Interventions: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone., Main Outcomes and Measures: The primary end point was the 2-year overall survival rate using intention-to-treat analysis., Results: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group., Conclusions and Relevance: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT02813967.

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.

Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRβ and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors. However, the function and molecular mechanism of SU6668 in prostate cancer has not been fully elucidated. In the present study, we found that SU6668 inhibited the proliferation and invasion of prostate cancer cells. Functional studies also demonstrated that SU6668 inhibited epithelial-mesenchymal transition in DU145 and LNCap cells. After treatment with SU6668, MTDH protein, which has been reported to be significantly overexpressed in many human tumor tissues, was downregulated in DU145 and LNCap cells. siRNA-mediated silencing of MTDH in prostate cancer cells decreased their proliferation and invasive capabilities, suggesting that SU6668 may inhibit cell proliferation and invasion of prostate cancer cells partly through downstream targeting of MTDH. Mechanistic investigations showed that AKT signaling pathway was inhibited after SU6668 treatment in prostate cancer cells. Moreover, a combination of SU6668 and PI3K-AKT pathway inhibitor LY29004 resulted in increased inhibition of cell proliferation and invasion in DU145 cells. Taken together, our findings revealed that SU6668 suppressed prostate cancer progression by downregulating MTDH/AKT signaling pathway and identified a promising therapeutic strategy for prostate cancer.

Objective: To evaluate and compare the effectiveness of double Endobutton technique and suture anchor combined Endobutton plate in the treatment of Tossy type III acromioclavicular joint dislocation., Methods: Between May 2010 and March 2014, a retrospective study was preformed on 56 patients with Tossy type III acromioclavicular joint dislocation. The coracoclavicular ligament was reconstructed with double Endobutton technique in 31 cases (Endobutton group), and with suture anchor combined Endobutton plate in 25 cases (Anchor group). There was no significant difference in age, gender, injury causes, injury side, associated injury, medical comorbidities, and disease duration between 2 groups (P>0.05). The operation time, medical device expenses, postoperative complications, preoperative and postoperative Constant-Murley scores, and postoperative Karlsson grading of the injured shoulder were compared between 2 groups., Results: The average operation time in Endobutton group was significantly greater than that in Anchor group (t = 4.285, P = 0.000); there was no significant difference in the medical device expenses between 2 groups (t = 1.555, P = 0.126). Primary healing of incision was obtained in all patients of 2 groups; no early complications of infection and skin necrosis occurred. All patients were followed up 15.6 months on average (range, 11-35 months). During follow-up, some loss of reduction and ectopic ossification in the coracoclavicular gap were observed in 1 case and 6 cases of Endobutton group, respectively. No recurrence of acromioclavicular joint dislocation, implant fixation loosening and broken, and secondary fractures occurred in the other patients. There was significant difference in the incidence of postoperative complications between 2 groups (P = 0.013). Constant-Murley scores of the injured shoulder significantly increased at 9 months after operation when compared with preoperative values in 2 groups (P < 0.05), but no significant difference was observed between 2 groups (P > 0.05). At last follow-up, there was no significant difference in Karlsson grading between 2 groups (Z = -0.628, P = 0.530)., Conclusion: Both double Endobutton technique and suture anchor combined Endobutton plate have good effectiveness in the treatment of Tossy type III acromioclavicular joint dislocation. But the latter is associated with easier operation, less operation time, and less complications.

Background: Laryngeal cancer is the one of the most prevalent cancer of the upper respiratory tract. Aiming to get a better understanding of the epidemiological characteristics and trends of laryngeal cancer in Zhejiang cancer registry in China during 2000-2011, we used the standardized quality control and statistical methods to analyze the incidence and mortality that were vital for making decision about laryngeal cancer prevention and control., Materials and Methods: Comparably high-quality data from eight population-based cancer registries in Zhejiang from 2000 to 2011 were qualified for analysis. The pooled data were stratified by area, sex, and age group. All incidence and mortality rates were age-standardized to the 2000 Chinese standard population and Segi's population, which were expressed per 100,000 populations. Average annual percent changes (AAPCs) and 95% confidence intervals of laryngeal cancer incidence and mortality were calculated for the temporal trends. The logarithmic trend line was also drawn to reflect the time trends of incidence and mortality., Results: During the 12 years, the 8 cancer registries covered a total of 81,758,277 person-year population (65,500,842 in urban and 16,257,435 in rural areas) including 41,315,911 person-year males and 40,442,366 person-year females. The age-standardized incidence rates were 1.10/10(5) by Chinese population and 1.12/10(5) by world population, respectively. The incidence of laryngeal cancer was relatively low in subjects under 44 years old. Then, it increased sharply after 45 years old and finally reached the peak in subjects of 75-79 years old. The age-standardized mortality rates of the Chinese population and world population were 0.28/10(5) and 0.35/10(5), respectively. The mortality of laryngeal cancer was at a low level in subjects under 49 years old. The rate dramatically increased in subjects over 50 years old, and then peaked in the age group of 80-84 years. The crude incidence of laryngeal cancer in Zhejiang cancer registration areas in 2000 was approximately 1.39/10(5), and it reached 1.78/10(5) in 2011, with the AAPC of 2.47%; the temporal trend line indicates that the incidence remained steady during the 12 years. The crude mortality of laryngeal cancer in Zhejiang registration areas in 2000 was about 0.30/10(5) and increased to 0.66/10(5), with the AAPC of 4.24% which showed no statistical significance; the temporal trend line indicates that mortality was going up to a certain extent, but not evident., Conclusions: Laryngeal cancer significantly influenced the quality of life for the patients. The comprehensive measures should be carried out to prevent the upward trend of laryngeal cancer.

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.

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.

Objective: To investigate the incidence and mortality rates of thyroid cancer in Zhejiang province during 2000 to 2009., Methods: The data of thyroid cancer were collected from six cancer registries in Zhejiang province and the incidence and mortality rates of thyroid cancer were analysed., Results: The mean annual incidence rate of thyroid cancer in Zhejiang cancer registration areas was 6.93/100 000 during 2000 to 2009, and male/female ratio was 1: 3.43. The incidence rate was 3.62/100 000 in 2000 and it increased to 11.42/100 000 in 2009, with the annual percent change (APC) of 16.32% (95% confidence interval: 12.90%-19.85%). The mean annual mortality rate of thyroid cancer was 0.27/100 000 during 2000 to 2009, and male/female ratio was 1: 1.12. The mortality showed a rising trend without a distinct fluctuation from 2000 to 2009, the APC was 2.14% (95% confidence interval: from -7.10% to 12.30%). The incidence showed a rising trend with the increase of ages after 15 years old, and peaked at 55-60 years old. The mortality was low before 54 years old, but showed a rising trend with a distinct fluctuation after 55 years old, and peaked at 85-90 years old., Conclusion: The prevention and control of risk factors for thyroid cancer in young and middle-aged people is key to decrease the incidence and mortality of thyroid cancer.

Objective: To investigate the incidence and mortality of brain tumor in Zhejiang cancer registration areas from 2000 to 2009., Methods: Data from 6 Cancer registration areas of Zhejiang province were collected. Number of cases, crude rates, proportions, age standardized rates, cumulate rates, cut rates, age-specific rates and annual percentage change (APC, 95% CI) of brain tumor incidence and mortality were analyzed., Results: There were 5 123 new diagnosed brain tumor cases in Zhejiang cancer registration areas, accounting for 3.14% of all the new cancer cases. The incidence rate of brain tumor was 8.53/100 000, and the standardized incidence rate by Chinese population was 5.72/100 000, ranking the 7th????? in cancer incidence spectrum of anatomic sites. Agespecific incidence of brain tumor increased along with age, and peaked among 70-74 age groups (24.09/100 000). The annual incidence rate of brain tumor increased from 2000 (6.87/100 000) to 2009(8.35/100 000), with APC as 1.58% (95%CI: -2.17%-5.47%, no statistical significance). A total of 2 357 deaths caused by brain tumor were reported from 2000-2009, accounting for 2.47% of all the cancer death cases. Mortality rate on brain tumor appeared to be 3.92/100 000, with the standardized mortality rate by Chinese population as 2.45/100 000, ranking the 7th????? in cancer mortality spectrum of anatomic sites. The age-specific mortality of brain tumor remained low among 0-39 year-olds, and reached the peak at 80-84 age groups (17.64/100 000). The annual mortality rate of brain tumor decreased from 2000(4.30/100 000)to 2009 (3.83/100 000) with minor fluctuation, and the APC was -0.65% (95%CI: -3.35%-2.12%, no statistical significance)., Conclusion: Brain tumors incidence and mortality in Zhejiang cancer registration areas were at a relatively high level. People who were at middle-age, especially above 70 years old should be the key targets for protection on this disease. Brain tumor incidence rates increased annually in Zhejiang, which should be called for attention.

Plasma lipid abnormalities are implicated in the pathogenic process of type 2 diabetes. The IDE-KIF11-HHEX gene cluster on chromosome 10q23.33 has been identified as a susceptibility locus for type 2 diabetes. We hypothesized that genetic variants at 10q23.33 may be associated with plasma lipid concentrations. Seven tagging single nucleotide polymorphisms (SNPs: rs7923837, rs2488075, rs947591, rs11187146, rs5015480, rs4646957 and rs1111875) at 10q23.33 were genotyped in 3,281 subjects from a Han Chinese population, using the TaqMan OpenArray and Sequenom MassARRAY platforms. Multiple linear regression analyses showed that SNP rs7923837 in the 3'-flanking region of HHEX was significantly associated with triglyceride levels (P = 0.019, 0.031 mmol/L average decrease per minor G allele) and that rs2488075 and rs947591 in the downstream region of HHEX were significantly associated with total cholesterol levels (P = 0.041, 0.058 mmol/L average decrease per minor C allele and P = 0.018, 0.063 mmol/L average decrease per minor A allele, respectively). However, the other four SNPs (rs11187146, rs5015480, rs4646957 and rs1111875) were not significantly associated with any plasma lipid concentrations in this Chinese population. Our data suggest that genetic variants in the IDE-KIF11-HHEX gene cluster at 10q23.33 may partially explain the variation of plasma lipid levels in the Han Chinese population. Further studies are required to confirm these findings in other populations.

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.

Although tobacco and alcohol consumption are the major risk factors of head and neck cancer (HNC), genetic variations of genes involved in several biological pathways, such as DNA repair genes, may affect an individual's susceptibility to HNC. However, few studies have investigated the associations between polymorphisms in DNA repair genes and HNC risk in the Chinese population. Thus, we genotyped five common, non-synonymous single-nucleotide polymorphisms (SNPs) [APEX1 (Asp148Glu), XRCC1 (Arg399Gln), ADPRT (Val762Ala), XPD (Lys751Gln) and XPG (His1104Asp)] in a hospital-based, case-control study of 397 HNC cases and 900 cancer-free controls in China. The results showed that none of the five SNPs in the DNA repair pathway was significantly associated with HNC risk, suggesting that these polymorphisms may not play a major role in HNC susceptibility in this Chinese population.

Background: Genome-wide association studies (GWAS) in populations of European ancestry have mapped a type 2 diabetes susceptibility region to chromosome 10q23.33 containing IDE, KIF11 and HHEX genes (IDE-KIF11-HHEX), which has also been replicated in Chinese populations. However, the functional relevance for genetic variants at this locus is still unclear. It is critical to systematically assess the relationship of genetic variants in this region with the risk of type 2 diabetes., Methodology/principal Findings: A fine-mapping study was conducted by genotyping fourteen tagging single-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetes in a Chinese Han population. Suggestive associations (P<0.05) observed from 1,200 cases and 1,200 controls in the first stage were further replicated in 1,725 cases and 2,081 controls in the second stage. Seven tagging SNPs were consistently associated with type 2 diabetes in both stages (P<0.05), with combined odds ratios (ORs) ranging from 1.14 to 1.33 in the combined analysis. The most significant locus was rs7923837 [OR = 1.33, 95% confidence interval (CI): 1.21-1.47] at the 3'-flanking region of HHEX gene. SNP rs1111875 was found to be another partially independent locus (OR = 1.23, 95% CI: 1.13-1.35) in this region that was associated with type 2 diabetes risk. A cumulative effect of rs7923837 and rs1111875 was observed with individuals carrying 1, 2, and 3 or 4 risk alleles having a 1.27, 1.44, and 1.73-fold increased risk, respectively, for type 2 diabetes (P for trend = 4.1E-10)., Conclusions/significance: Our results confirm that genetic variants of the IDE-KIF11-HHEX region at 10q23.33 contribute to type 2 diabetes susceptibility and suggest that rs7923837 may represent the strongest signal related to type 2 diabetes risk in the Chinese Han population.

Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility. Its pathophysiology is largely unknown, and few genetic influences have been defined. To identify common variants contributing to NOA in Han Chinese men, we performed a three-stage genome-wide association study of 2,927 individuals with NOA and 5,734 controls. The combined analyses identified significant (P < 5.0 × 10(-8)) associations between NOA risk and common variants near PRMT6 (rs12097821 at 1p13.3: odds ratio (OR) = 1.25, P = 5.7 × 10(-10)), PEX10 (rs2477686 at 1p36.32: OR = 1.39, P = 5.7 × 10(-12)) and SOX5 (rs10842262 at 12p12.1: OR = 1.23, P = 2.3 × 10(-9)). These findings implicate genetic variants at 1p13.3, 1p36.32 and 12p12.1 in the etiology of NOA in Han Chinese men.