Cancer In Chinese Population Research Articles

Diagnostic value of tumor associated autoantibody panel in early detection of lung cancer in Chinese population: Protocol for a prospective, observational, and multicenter clinical trial

Lung cancer is the leading cause of cancer deaths. Although targeted therapies and programmed cell death protein 1 (PD-1) blockade have offered great advances, five-year survival rates remained low. Diagnosis of lung cancer at an earlier stage is the most efficient approach to improve survival. Tumor associated autoantibodies (TAAb) have been proven a promising innovative biomarker of lung cancer. We aimed to comprehensively evaluate the sensitivity, specificity, and accuracy of TAAbs in lung cancer detection, especially in early-stage patients, through a multicenter prospective observational clinical trial, and to screen out the novel combination of TAAbs with the best detection value for Chinese population. We aimed to enroll 1,400 participants from three clinical centers and divide into two cohorts. One cohort is participants with newly pathologically confirmed lung cancer as the case cohort, and the other is participants with benign nodules, matched healthy controls and other benign lung diseases as the control cohort. Cases and controls were randomly distributed into training or validation set. The level of 14 autoantibody candidates in their plasma were detected. A Monte-Carlo Simulated Annealing method was implemented to develop a composite panel of autoantibodies to distinguish between matched lung cancer cases and controls in the training set. The newly developed autoantibody panel was tested in the validation set for sensitivity, specificity and accuracy. This is the first and largest clinical trial designed to develop a novel autoantibody panel for lung cancer detection specifically for Chinese people. We performed a multicenter, prospective, observational study to find a novel panel of autoantibody markers that can help the diagnosis of lung cancer and the characterization of pulmonary nodules in Chinese population. The results may help to provide evidence-based recommendations to clinicians for lung cancer early detection and pulmonary nodule management. This study is registered in the ClinicalTrials.gov (NCT04216511).

Cost-effectiveness of lung cancer screening combined with nurse-led smoking cessation intervention: A population-based microsimulation study

BackgroundThe appropriate screening inclusion criteria of low-dose computed tomography screening for lung cancer in Chinese population remains unclear and the effect of combining screening with nurse-led smoking cessation intervention is poorly understood as well. ObjectiveWe compared the benefits and costs of lung cancer screening with and without nurse-led smoking cessation intervention in different inclusion criteria to help select optimal screening strategies. MethodsDifferent screening strategies were set based on diverse starting ages, smoking pack-year and whether nurse-led smoking cessation intervention was applied. We use nationally representative data published by the China Health and Retirement Longitudinal Survey, based on a microsimulation model, to predict incremental cost-effectiveness ratio and net health benefits under different strategies. ResultsThe incremental cost-effectiveness ratios for all lung cancer screening strategies were less than three times GDP per capita, and screening combined with smoking cessation intervention had lower incremental cost-effectiveness ratios. The largest net health benefits and probability of cost-effectiveness were both obtained in the strategy which conducted screening and nurse-led smoking cessation intervention for people over 45 years with at least 20 pack-year smoking history. In strategies screening alone, it was obtained in screening for people over 50 years and with at 20 pack-year smoking history. ConclusionsNurse-led smoking cessation intervention is recommended provided in conjunction with lung cancer screening. The optimal strategy is conducted screening with cessation intervention for current smokers or smoking quitters in the past 15 years who are over 45 years with at least 20 pack-year smoking history. For strategies screening alone, the target population should be over 50 years old with at least 20 pack year smoking history, when willingness to pay less than three times GPD per capita.

Preferences for oral nutritional supplement therapy among postoperative patients with gastric cancer: a discrete choice experiment.

PurposesPatients after gastrectomy have poor compliance with oral nutritional supplement (ONS) therapy. Incorporating patient preferences into treatment decisions allows possible product improvements or treatment focus adjustments. The purpose of this research was to investigate the preferences for ONS therapy among postoperative patients with gastric cancer, and to provide person-centered oral nutrition management strategies.MethodsA discrete choice experiment was designed and implemented within a Chinese cancer population. The survey was administered via paper-based questionnaires during face-to-face interviews with assistance from health professionals. A mixed logit model was used to estimate respondents’ preferences for different levels of nutrition therapy attributes.ResultsOne hundred ninety respondents valued “Adverse reactions-almost none” (β 3.43 [SE, 0.28]) the most, followed by “Flavor-good taste” (β 0.68 [SE, 0.13]) and “Follow-up frequency-once every 2 weeks” (β 0.52 [SE, 0.13]), and were willing to pay more for these attribute levels. Respondents would be 93.73% more likely to accept a nutrition therapy program if there were almost no adverse reactions compared to the frequent adverse reactions.ConclusionsHealth professionals should pay attention to the management and prevention of adverse reactions when prescribing nutritional products, and provide diversified ONS products when necessary to meet patient preferences. When formulating intervention strategies, health professionals should also consider the different characteristics of patients, acknowledge the importance of the role of nurse specialists in a novel model of multidisciplinary nutritional care, standardize ONS information, follow up regularly, and encourage patients’ families to participate in daily nutrition care.Supplementary informationThe online version contains supplementary material available at 10.1007/s00520-022-07154-8.

TLR4 regulatory region variants reduce the susceptibility of small-cell lung cancer in Chinese population.

Toll-like receptors (TLRs) participate in the induction and regulation of immune responses and are closely related to the occurrence and development of small-cell lung cancer (SCLC). This study aimed to investigate the impact of polymorphisms in the regulatory regions of TLRs on the susceptibility of SCLC. The case-control study included 304 SCLC patients and 304 healthy controls. TLRs gene polymorphisms were genotyped by PCR-restrictive fragment length polymorphism analysis and TaqMan assay. Unconditional logistic regression was used to estimate odds ratio (OR) and its 95% confidence interval (95% CI). Our results showed that TLR4 rs1927914 GG genotype and TLR4 rs7869402 TT genotype reduced the risk of SCLC with OR (95% CI) of 0.54 (0.32-0.90) and 0.47 (0.28-0.80), respectively. Stratified analysis suggested that TLR4 rs1927914 GG genotypes significantly reduced the risk of SCLC among male (OR = 0.35; 95% CI, 0.18-0.69; P < 0.01), the younger patients (OR = 0.49; 95% CI, 0.26-0.94; P = 0.03) and non-drinkers (OR = 0.47; 95% CI, 0.24-0.89; P = 0.02). TLR4 rs7869402 CT or TT genotype significantly reduced the susceptibility to SCLC among male patients (OR = 0.37; 95% CI, 0.19-0.71, P < 0.01), the younger patients (OR = 0.41; 95% CI, 0.22-0.79; P < 0.01), smokers (OR = 0.25; 95% CI, 0.10-0.60; P < 0.01) and drinkers (OR = 0.31; 95% CI, 0.11-0.88; P = 0.03). TLR3 rs5743303, TLR4 rs11536891, TLR5 rs1640816 and TLR7 rs3853839 had no significant correlation with the risk of SCLC. These findings emphasized the important role of TLR4 in the development of SCLC.

Screening methods for colorectal cancer in Chinese populations.

Screening methods for colorectal cancer in Chinese populations.

Associations of systemic inflammation markers with identification of pulmonary nodule and incident lung cancer in Chinese population.

ObjectivesNeutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII), easily accessible systemic inflammation response parameters, were reported to associate with poor lung cancer prognosis. However, research on the effects of these markers on the risk of positive nodules (PNs) and lung cancer is limited.MethodsParticipants in this retrospective study were those who had their first computed tomography (CT) screening at Jiangsu Province Hospital's Health Promotion Center between January 1, 2017 and December 31, 2020. We identified PNs (≥6 mm in diameter) from free text of CT reports and lung cancer from medical records. Multivariate logistic analysis was used to assess the association between NLR, PLR, or SII and PNs or lung cancer.ResultsThe detected rate of PNs was 9.60% among the 96,476 participants. Age, smoking and body mass index were possible influencing factors for PNs. We observed linear dose‐effect relationship between NLR, PLR, or SII and PNs (p non‐linear > 0.05). Compared with low quintile, participants with top quintiles of NLR, PLR or SII had an increased risk of PNs, with the adjusted ORs of 1.19 (1.11–1.28), 1.11 (1.04–1.19) or 1.11 (1.03–1.18), respectively. Meanwhile, NLR showed the U‐shaped relationship with lung cancer, with adjusted ORs of 1.40 (1.08–1.81) comparing highest NLR quintile to the third quintile. The high PLR and SII showed significantly associated with lung cancer with adjusted ORs of 1.29 (0.99–1.68) and 1.35 (1.04–1.74) comparing to the lowest quintile.ConclusionsThe high levels of systemic inflammation markers were associated with the risk of positive pulmonary nodules and lung cancer, which suggested systemic immune response may be an important pre‐clinical feature for the early identification of diseases.

The distinct genetic features of pancreatic cancer in Chinese population.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with unclear genetic foundation. Genetic association studies with large cohort were extensively performed but not for East Asian population especially for Chinese Population. To date, little is known about racial disparities in the genetic landscape of PDAC. Significantly higher rate of EGFR mutation in Chinese lung cancer patients bring about a new era of lung cancer treatment, leading to a remarkably improved survival. Therefore, understanding the distinct genetic features of PDAC in Chinese population is warranted and could possibly change the paradigm of PDAC management.

Assessment of the efficacy and safety of intraperitoneal chemotherapy in patients with advanced gastric cancer in Chinese population: a meta-analysis

To investigate the safety and efficacy of intraoperative intraperitoneal chemotherapy in treating advanced gastric cancer. A randomized controlled trial (RCT) of gastric cancer surgery combined with intraoperative intraperitoneal chemotherapy for the efficacy and safety were screened by computer search PubMed, Medline, Springer, Elsevier Science Direct, Weipu, Wanfang and China National Knowledge Infrastructure (CNKI) with the last report up to October 2019. The control group underwent radical gastrectomy, and the experimental group underwent intraoperative intraperitoneal chemotherapy and radical gastrectomy. A total of 997 (Experimental group 453; Control group 544) participants were considered in this meta-analysis. Compared with the control group, the experimental group has higher 1-year survival rate [OR=2.40, 95%CI (1.34, 4.33), P=0.003], 2-year survival rate [OR=3.45, 95%CI (2.08, 5.75), P<0.00001], 3-year survival rate [OR=2.70, 95%CI (2.05, 3.54), P<0.00001] and 5-year survival rate [OR=2.90, 95%CI (1.93, 4.37), P<0.00001]. There is no significant difference in postoperative bleeding (P=0.95), postoperative infection (P=0.26), postoperative anastomotic leakage (P=0.41), and postoperative intestinal obstruction (P=0.11). Intraoperative intraperitoneal chemotherapy with advanced gastric cancer in the Chinese population can improve patients’ survival rate after surgery and does not increase the incidence of postoperative complications, so it is clinically significant and safe.

Association of p73 G4C14-A4T14 and p53 codon 72 polymorphism with cervical cancer in Chinese population.

Cervical cancer is known to be the fourth most common cancer among women globally. In various factors, genetic factors have been considered as one major risk factor for cervical cancer. The research of genetic susceptibility to cervical cancer can be greatly helpful in studying the complex mechanism. This study was conducted to identify whether polymorphic variants of p73 G4C14-A4T14 and tumor protein p53 (p53) codon 72, either independently or jointly, might be associated with the risk of cervical cancer. The genotypes of p73 G4C14-A4T14 and p53 codon 72 polymorphisms of peripheral blood DNA from 190 cervical cancer patients and 210 controls were investigated using polymerase chain reaction with confronting two-pair primers and polymerase chain reaction-restriction fragment length polymorphism, respectively. The frequency of p73 G4C14-A4T14 AT/AT (P = 0.013) or p53 codon 72 GG (P = 0.026) genotype was associated with an increased risk of cervical cancer by comparing with the p73 G4C14-A4T14 GC/GC or p53 codon 72 CC genotype, respectively. In addition, the interaction between the p73 G4C14-A4T14 and p53 codon 72 polymorphisms increased the risk of cervical cancer in a multiply manner, with the odds ratio being 3.692 (95% confidence interval =2.106-6.473) for subjects carrying both p73 G4C14-A4T14 GC/AT+AT/AT and p53 codon 72 GG genotypes. These results suggest that there is a statistical difference between p73 and p53 gene polymorphism and the risk of cervical cancer in Chinese women, and there is a potential gene-gene interaction in the incidence of cervical cancer.

Germline Mutational Profiles and Clinicopathological Features Of Hereditary Breast Cancer In Chinese Population

Germline Mutational Profiles and Clinicopathological Features Of Hereditary Breast Cancer In Chinese Population

The relationship between XPD Asp312Asn Polymorphism and esophageal cancer in Chinese population: a meta-analysis

It has been reported that xeroderma pigmentosum group D (XPD) Asp312Asn is related to esophageal cancer (EC). Nevertheless, in 12 recent years, some researchers have put forward different points of view. Thus, we aimed to investigate the relation between XPD Asp312Asn polymorphism and the risk of EC in Chinese. Related studies were searched in the databases between the beginning to October 2019. An OR with 14 the corresponding 95% CI was carried out to appraise the relevance. There were 8 studies with 2553 esophageal cancer cases and 3091 controls in 15 this meta-analysis. Due to no heterogeneities among the selected studies of all the four genetic models, fxed-effect model was used in each genotype. There was not significant relationship between XPD Asp312Asn polymorphism and EC in overall analyses by pooled ORs and subgroup analyses stratified by geographic area and source of controls. In conclusion, there may be not association between XPD Asp312Asn polymorphism and EC in Chinese populations. Further studies about other ethnic groups are needed to confirm this conclusion.

Diagnostic value of exosome derived long noncoding RNA in gastric cancer in Chinese population: A PRISMA-compliant systematic review and meta-analysis.

Background:Objective to systematically evaluate the diagnostic value of long noncoding RNA (lncRNA) in gastric cancer (GC) in the Chinese population.Methods:PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, and Wanfang Database were searched. According to the search strategy and inclusion and exclusion criteria, 2 staff members screened the relevant kinds of literature from January 2010 to December 2020 and extracted the relevant data. Revman5.3, Meta-Disc1.4, and Stata15.1 software were used to analyze the relationship between lncRNA from exosomes and the diagnosis of GC. The combined values of sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic curve was drawn and the area under the ROC curve (AUC) value was calculated.Results:In 9 studies, 1314 samples were included, including 792 cases in the case group and 522 cases in the control group. The combined SEN was 0.82 (95% CI: 0.77–0.86), the combined SPE was 0.78 (95% CI: 0.72–0.83), the combined positive likelihood ratio was 3.7 (95% CI: 2.9–4.6), the negative likelihood ratio was 0.23 (95% CI: 0.18–0.29), and the DOR was 16 (95% CI: 12–23), AUC was 0.87 (95% CI: 0.84–0.90). Subgroup analysis showed that the SEN, SPE, likelihood ratio, DOR, and AUC of plasma-derived lncRNA in the diagnosis of GC were better than those of serum.Conclusions:Exosome-derived lncRNA may be a new potential biomarker for the clinical diagnosis of GC.

Polymorphisms in lncRNA MIR2052HG and susceptibility to breast cancer in Chinese population.

Background: Published studies based on pharmacokinetics have explored the relationship between the lncRNA MIR2052HG and the prognosis of breast cancer (BC) resistance and recurrence. However, the underlying association of MIR2052HG SNPs with BC development remains unclear.Methods: Combining bioinformatics and databases, SNPs (Single Nucleotide Polymorphisms) in the MIR2052HG gene were screened, and SNPs in the lncRNA MIR2052HG were selected for genotyping among 504 Chinese Han patients and 505 healthy controls, which were frequency-matched for age (±2 years). Logistic regression analysis was used to explore the association between MIR2052HG SNPs and the BC risk. Interactions between the MIR2052HG SNPs and reproductive factors were further evaluated using the multifactor dimensionality reduction (MDR) method. qRT–PCR was performed to detect MIR2052HG expression in individuals with different genotypes of rs34841297. The target miRNA, miR-4456 of MIR2052HG rs34841297 was predicted by websites and confirmed by performing dual luciferase gene reporter assays. CCK-8 and Transwell experiments were designed to explore the effects of miR-4456 on the proliferation, invasion and migration of BC cells.Results: In this study, nine SNPs were screened. After adjusting for age, menarche age, menopausal status, number of pregnancies, history of abortions, breast feeding history and family history of BC, the results of the logistic regression analysis showed the rs34841297 A/- gene polymorphism was positively correlated with the incidence of BC. Compared with the AA genotype, patients with the A-+-- genotype of rs34841297 at age<50 years, and menarche age<14 years, Premenopausal status, history of abortion, no history of breastfeeding and no family history of tumors in first-degree relatives had an increased risk of BC. MDR results revealed that individuals with rs34841297 - (homozygous deletion) of the A allele who were not menopausal and had no history of breastfeeding had a higher risk of BC. qRT–PCR results revealed that homozygous deletion (1.68±1.37) of the rs34841297 A- genotype resulted in higher MIR2052HG expression than the heterozygous deletion genotype (0.95±0.94) and wild AA genotype (0.26±0.12). Binding between MIR2052HG and miR-4456 was occurred when rs34841297 carried the AA genotype. Moreover, preliminary functional studies indicated that the overexpression of miR-4456 increased the proliferation, invasion and migration of BC cells.Conclusion: Our study showed that the MIR2052HG gene polymorphism may be related to BC susceptibility, and the MIR2052HG rs34841297 A/- genotype may probably affect the proliferation, invasion and migration of BC cells by modulating the interactions with of miR-4456.

Potential pleiotropism of cancer-related single nucleotide polymorphisms among Chinese population

Objective: To investigate the potential pleiotropism of cancer-related single nucleotide polymorphisms (SNPs) among Chinese population. Methods: Based on the catalogue of GWAS jointly constructed by the National Human Genome Research Institute and the European Institute of Bioinformatics, according to population origin (Chinese population and non-Chinese population) and disease traits (cancer and non-cancer traits). All SNPs found by GWAS before August 2020 were divided into four categories: cancer in Chinese population, non-cancer in Chinese population, cancer in non-Chinese population and non-cancer in non-Chinese population. The number, correlation and linkage of the four categories of SNPs were described. Results: By August 2020, a total of 196 813 SNPs from 4 096 GWAS were included in the GWAS directory. The information that SNPs refer to unknown or were not related to the disease was excluded, and 117 441 independent SNPs were finally included. There were 619 SNPs related to cancer and 9 569 SNPs related to non-cancer disease in Chinese population, respectively. There were 4 624 SNPs related to cancer and 106 448 SNPs related to non-cancer disease (trait) in non-Chinese population, respectively. Three SNPs, rs2736100, rs6983267 and rs401681, were associated with two or more types of cancer in both Chinese and non-Chinese populations. Seven SNPs, rs7705526, rs2736100, rs10993994, rs2735839, rs4430796, rs174537 and rs9271588, were associated with cancer and non-cancer diseases in both Chinese and non-Chinese populations, respectively. Conclusion: There is a potential pleiotropism of cancer-related SNPs in Chinese population.

A Functional Polymorphism in Accessible Chromatin Region Confers Risk of Non-Small Cell Lung Cancer in Chinese Population.

BackgroundThe disease-associated non-coding variants identified by genome-wide association studies (GWASs) were enriched in open chromatin regions (OCRs) and implicated in gene regulation. Genetic variants in OCRs thus may exert regulatory functions and contribute to non-small cell lung cancer (NSCLC) susceptibility.ObjectiveTo fine map potential functional variants in GWAS loci that contribute to NSCLC predisposition using chromatin accessibility and histone modification data and explore their functions by population study and biochemical experimental analyses.MethodsWe mapped the chromatin accessible regions of lung tissues using data of assay for transposase-accessible chromatin using sequencing (ATAC-seq) in The Cancer Genome Atlas (TCGA) and prioritized potential regulatory variants within lung cancer GWAS loci by aligning with histone signatures using data of chromatin immunoprecipitation assays followed by sequencing (ChIP-seq) in the Encyclopedia of DNA Elements (ENCODE). A two-stage case–control study with 1,830 cases and 2,001 controls was conducted to explore the associations between candidate variants and NSCLC risk in Chinese population. Bioinformatic annotations and biochemical experiments were performed to further reveal the potential functions of significant variants.ResultsSixteen potential functional single-nucleotide polymorphisms (SNPs) were selected as candidates from bioinformatics analyses. Three variants out of the 16 candidate SNPs survived after genotyping in stage 1 case–control study, and only the results of SNP rs13064999 were successfully validated in the analyses of stage 2 case–control study. In combined analyses, rs13064999 was significantly associated with NSCLC risk [additive model; odds ratio (OR) = 1.17; 95%CI, 1.07–1.29; p = 0.001]. Functional annotations indicated its potential enhancer bioactivity, and dual-luciferase reporter assays revealed a significant increase in luciferase activity for the reconstructed plasmid with rs13064999 A allele, when compared to the one with wild-type G allele (pA549 < 0.001, pSK-MES-1 = 0.004). Further electrophoretic mobility shift assays (EMSA) and super-shift assays confirmed a stronger affinity of HP1γ for the binding motif containing SNP rs13064999 A allele.ConclusionThese findings suggested that the functional variant rs13064999, identified by the integration of ATAC-seq and ChIP-seq data, contributes to the susceptibility of NSCLC by affecting HP1γ binding, while the exact biological mechanism awaits further exploration.

Identification and epidemiological evaluation of gastric cancer risk factors: based on a field synopsis and meta-analysis in Chinese population.

To summarize and assess the credibility and strength of non-genetic factors and genetic variation on gastric cancer risk, we performed a field synopsis and meta-analysis to identify the risk of gastric cancer in Chinese population. Cumulative evidence was graded according to the Venice criteria, and attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to evaluate the epidemiological effect. A total of 956 studies included non-genetic (404 studies) and genetic factors (552 studies) were quantified, and data on 1161 single nucleotide polymorphisms (SNPs) were available. We identified 14 non-genetic factors were significantly associated with gastric cancer risk. For the analysis of time trends, H. pylori infection rate in gastric cancer and population showed a downward trend. Meanwhile 22 variants were identified significantly associated with gastric cancer: 3 (PLCE1 rs2274223, PSCA rs2976392, MUC1 rs4072037) were high and 19 SNPs were intermediate level of summary evidence, respectively. For non-genetic factors, the top three for ARP were 54.75% (pickled food), 65.87% (stomach disease), and 49.75% (smoked and frying). For PARP were 34.22% (pickled food), 34.24% (edible hot food) and 23.66%(H. pylori infection). On the basis of ARP and PARP associated with SNPs of gastric cancer, the top three for ARP were 53.91% (NAT2, rs1799929),53.05% (NAT2 phenotype), and 42.85% (IL-10, rs1800896). For PARP (Chinese Han in Beijing) were 36.96% (VDR, rs731236), 25.58% (TGFBR2, rs3773651) and 20.56% (MUC1, rs4072037). Our study identified non-genetic risk factors and high-quality biomarkers of gastric cancer susceptibility and their contribution to gastric cancer.

Cost-effectiveness of anti-tumor associated antigen autoantibody screening for hepatocellular carcinoma in the population with chronic hepatitis B-related cirrhosis

Objective: To evaluate the cost-effectiveness of anti-tumor associated antigen autoantibody (TAAb) for hepatocellular carcinoma (HCC) screening in cirrhosis population with chronic hepatitis B (CHB). Methods: A simulated cohort of 40-year-old patients with CHB cirrhosis was established with a sample size of 10 000. Using TAAb screening alone or TAAb and AFP screening in parallel (TAAb + AFP) as the research strategy, and liver ultrasound and AFP screening in parallel (liver ultrasound + AFP) as the control strategy, the decision analysis Markov model was constructed and the model validity was evaluated. The 6-month cycle was simulated using TreeAge Pro 2020 software. Cost and quality-adjusted life years (QALY) were calculated. Incremental cost-effectiveness ratio (ICER) was used to compare the two strategies, and sensitivity analysis was used to evaluate the uncertainty of results. Results: The Markov model had a total of 11 outcomes, of which 7 were natural outcomes and 4 wereclinical intervention outcomes, and the goodness of fit was 0.969. The lifetime screening cost of TAAb+AFP strategy for HCC screening was 249 612 yuan/case, and the QALY per capita was 7.704 years. Compared with liver ultrasound +AFP strategy (247 805 yuan/case), the total health cost increased by 1 807 yuan/case, and the QALY obtained was 0.014. The ICER was 127 635 yuan /QALY. When the TAAb screening fee was higher than 889.552 yuan, or the discount rate was higher than 0.068, or the antiviral treatment compliance was lower than 45.1%, ICER > 212 676 yuan /QALY. When the single TAAb screening fee was 400-600 yuan, the TAAB+AFP strategy had cost effective value. When the willingness to pay was 70 892, 141 784 and 212 676 yuan /QALY, the probability of cost-effectiveness of TAAb+AFP strategy was 70.6%, 75.3% and 77.8%, respectively. Conclusion: It is cost-effective to use TAAb+AFP for early screening of liver cancer in Chinese population with CHB cirrhosis.

Genome-wide gene-smoking interaction study identified novel susceptibility loci for non-small cell lung cancer in Chinese populations.

Gene-smoking interactions play important roles in the development of non-small cell lung cancer (NSCLC). To identify single-nucleotide polymorphisms (SNPs) that modify the association of smoking behavior with NSCLC risk, we conducted a genome-wide gene-smoking interaction study in Chinese populations. The genome-wide interaction analysis between SNPs and smoking status (ever- versus never-smokers) was carried out using genome-wide association studies of NSCLC, which included 13 327 cases and 13 328 controls. Stratified analysis by histological subtypes was also conducted. We used a genome-wide significance threshold of 5 × 10-8 for identifying significant gene-smoking interactions and 1 × 10-6 for identifying suggestive results. Functional annotation was performed to identify potential functional SNPs and target genes. We identified three novel loci with significant or suggestive gene-smoking interaction. For NSCLC, the interaction between rs2746087 (20q11.23) and smoking status reached genome-wide significance threshold [odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.54-0.74, P = 3.31 × 10-8], and the interaction between rs11912498 (22q12.1) and smoking status reached suggestive significance threshold (OR = 0.72, 95% CI: 0.63-0.82, P = 8.10 × 10-7). Stratified analysis by histological subtypes identified suggestive interactions between rs459724 (5q11.2) and smoking status (OR = 0.61, 95% CI: 0.51-0.73, P = 7.55 × 10-8) in the risk of lung squamous cell carcinoma. Functional annotation indicated that both classic and novel biological processes, including nicotine addiction and airway clearance, may modulate the susceptibility to NSCLC. These novel loci provide new insights into the biological mechanisms underlying NSCLC risk. Independent replication in large-scale studies is needed and experimental studies are warranted to functionally validate these associations.

LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis.

Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P<0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.

Clinicopathological and genomic characteristics of POLE-mutated colorectal cancer in a Chinese population.

e15531 Background: DNA polymerase ε (POLE) is essential for proofreading and fidelity in DNA replication and repair. Previous studies found that mutation in POLE associated with higher tumor mutational burden (TMB), which is an approved biomarker for immunotherpy in solid tumors. However, the clinicopathological and mutational analyses of POLE-mutated colorectal cancer in a large Chinese population have not yet been reported. Methods: Hybrid capture-based next-generation sequencing (NGS) were performed in 4628 samples of colorectal tumors and matched normal pairs in a CAP/CLIA-approved laboratory (3DMed). NGS testing for gene mutations, TMB and MSI was implemented. Results: Of 4628 colorectal cancer patients, POLE mutations were observed in 67 patients (1.45%). A total of 11 different POLE mutations were identified, mostly associated with exonucleas domain. P286R(32,0.69%), V411L(13,0.28%), A456P(7,0.15%), S459F(3,0.06%) and S297F(3,0.06%) were the most frequently mutated sites of POLE. We also detected 1 V758L and 1 W1130R mutation outside the exonuclease domain in separate cases. Among the 4628 patients, 2157 patients were detectable for TMB by NGS panel, including 2128 POLE wild type and 29 POLE mutation patients. The TMB of patients with POLE mutations was significantly higher than that in wide type POLE tumors (mean TMB 252.3 vs 13.4 muts/Mb, P ＜0.0001). All the 29 POLE-mutated patients were TMB-H (≥10 muts/Mb) and 28 of them were MSS. A MSS patient with metastatic colon cancer harboring A456P POLE mutation responsed well to the immunotherpy and achieved a partial response. Conclusions: Our results realved a remarkable positive correlation between POLE mutation and TMB level in a Chinese colorectal cancer population, which suggests POLE gene will be a promising biomarker of immunotherpy for MSS colorectal tumor.[Table: see text]