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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]

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]

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]

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]

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]

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]

Two recent genome-wide association studies reported significant associations of genetic variants at 1q22, 10q23 and 20p13 with gastric cancer (GC) risk in Chinese populations. However, these findings have not been confirmed in other independent studies. Here, we performed an independent case–control study in a Chinese population by genotyping three loci (rs4072037A>G at 1q22, rs2274223A>G at 10q23 and rs13042395C>T at 20p13) in 1681 GC cases and 1858 controls. We found that rs4072037 at 1q22 and rs2274223 at 10q23 were significantly associated with risk of GC with per allele odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.63–0.81; P = 2.98 × 10−7] and 1.42 (95% CI: 1.27–1.58; P = 9.68 × 10−10), respectively. The association was more prominent for rs2274223 in female (OR = 1.86, 95% CI: 1.49–2.32) and gastric cardia adenocarcinoma (GCA) (OR = 1.71, 95% CI: 1.49–1.95). Furthermore, we combined the two single-nucleotide polymorphisms to evaluate the joint effect and found that the GC risk significantly increased with the number of risk allele increasing with a trend P value of 6.66 × 10−16, and individuals with four risk alleles had a 3.28-fold (95% CI: 1.75–6.13) risk of GC compared with those having no risk alleles. However, no significant association was detected between rs13042395 at 20p13 and GC risk (OR = 1.04, 95% CI: 0.94–1.15; P = 0.452). In conclusion, our results indicate that genetic variants at 1q22 and 10q23 but not 20p13 may serve as candidate markers for GC susceptibility in the Chinese population. [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]

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]

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]

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]

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]

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. [ABSTRACT FROM AUTHOR]