An increasing number of publications had reported the association between single‐nucleotide polymorphisms (SNPs) and esophageal cancer (EC) risk in the past decades. Results from these publications were controversial. We used PubMed, Medline, and Web of Science to identify meta‐analysis articles published before 30 July 2018, that summarize a comprehensive investigation for cumulative evidence of genetic polymorphisms of EC and its subtype risk. Two methods, Venice criteria and false‐positive report probability (FPRP) tests, were used to assess cumulative evidence of significant associations. At last, 107 meta‐analyses were considered to be in conformity with the inclusion criteria, yielding 51 variants associated with EC or esophageal squamous cell carcinoma (ESCC). Thirty‐eight variants were considered to be nominally significant associated with risk of EC or ESCC, whereas the rest showed non‐association. In additional, five variants on five genes were rated as strong cumulative epidemiological evidence for a nominally significant association with EC and ESCC risk, including CYP1A1 rs1048943, EGF rs444903, HOTAIR rs920778, MMP2 rs243865, and PLCE1 rs2274223, 10 variants were rated as moderate, and 18 variants were rated as weak. Additionally, 17 SNPs were verified noteworthy in six genomewide association studies (GWAS) using FPRP methods. Collectively, this review offered a comprehensively referenced information with cumulative evidence of associations between genetic polymorphisms and EC and ESCC risk.

Background and Aim:A large number of papers reporting the relationships between body mass index (BMI) and esophageal cancer (EC) risk have been published in the past few decades; however, these results are inconsistent. Therefore, we carried out meta-analyses to explore the relationships between BMI and the risk of EC (including esophageal squamous cell carcinoma [ESCC] and esophageal adenocarcinoma [EADC]). Methods: We used the Web of Science, PubMed, and Embase to identify all published/online articles before December 30, 2018, which yielded 25 articles eligible for data extraction (including 16,561 cases and 11,954,161 controls), and then pooled the relative risks (RRs) and corresponding 95% confidence intervals (CIs) using randomeffects model. Results: Our study presented that underweight had statistically significant association with the risk of EC (RR = 1.78, 95% CI = 1.48, 2.14, P < 0.001) and ESCC (RR = 1.57, 95% CI = 1.20, 2.06, P = 0.001) when compared with normal weight. Interestingly, both overweight and obesity could increase the risk of EADC (RR = 1.56, 95% CI = 1.42, 1.71, P < 0.001; RR = 2.34, 95% CI = 2.02, 2.70, P < 0.001) while decrease the risk of ESCC (RR = 0.71, 95% CI = 0.60, 0.84, P < 0.001; RR = 0.63, 95% CI = 0.60, 0.84, P = 0.002). Additionally, obesity could increase the risk of EC (RR = 1.51, 95% CI = 1.21, 1.89, P < 0.001). Conclusion: These meta-analyses provide a comprehensive and updated epidemiological evidence to confirm the associations between BMI and EC risk. These findings have public health implications with respect to better control bodyweight and then reduce the occurrence of EC (including ESCC and EADC).Body mass index and esophageal cancer risk J Tian et al. Figure 2The forest plot of overall effect for association between underweight subjects and esophageal cancer risk. Figure 3 The forest plot of overall effect for association between underweight subjects and esophageal squamous cell carcinoma risk. at wileyonlinelibrary.com] [Color figure can be viewed [Color figure can be viewed at wileyonlinelibrary.com] J Tian et al. Body mass index and esophageal cancer risk

Background: Brain metastasis (BM) causes high morbidity and mortality rates in lung cancer (LC) patients. The present study aims to develop models for predicting the development and prognosis of BM using a large LC cohort. Methods: A total of 266,522 LC cases diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program cohort. Risk factors for developing BM and prognosis were calculated by univariable and multivariable logistic and Cox regression analysis, respectively, and nomograms were constructed based on risk factors. Nomogram performance was evaluated with receiver operating characteristics (ROC) curve, or C-index and calibration curve. Results: The prevalence of BM was 13.33%. Associated factors for developing BM include: advanced age;Asian or Pacific Islander race; uninsured status; primary tumor site; higher T stage; higher N stage; poorly differentiated grade; the presence of lung, liver, and bone metastases; and adenocarcinoma histology. Median overall survival (OS) was 4 months; associated prognosis factors were similar to risk factors plus female gender, unmarried status, and surgery. The calibration curve showed good agreement between predicted and actual probability, and the AUC/C-index was 73.1% (95% CI: 72.6-73.6%) and 0.88 (95% CI: 0.87-0.89) for risk and prognosis predictive models, respectively.Conclusions: BM was highly developed in LC patients, and homogeneous and heterogeneous factors were found between risk and prognosis for BM. The nomogram showed good performance in predicting BM development and prognosis.

Objective In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms (SNPs) on candidate genes and gastric cancer (GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC. Methods We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability (FPRP) test. Results Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1 (rs1760944), DNMT1 (rs16999593), ERCC5 (rs751402), GSTT1 (null/presence), MDM2 (rs2278744), PPARG (rs1801282), TLR4 (rs4986790), IL-17F (rs763780), and CASP8 (rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies. Conclusions Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk; however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.

BackgroundGenetic studies have previously reported that single-nucleotide polymorphisms (SNPs) in CHRNA genes (such as CHRNA3, CHRNA4, CHRNA5, or CHRNA3-CHRNA5-CHRNB4 clusters) are linked to the risk of neoplastic and non-neoplastic diseases. However, these conclusions were controversial and no systematic research synopsis has been available. We aimed to synthesize current knowledge of variants in the CHRNA genes on the risk of diseases.MethodsWe systematically searched for publications using PubMed, Medline, and Web of Science on or before 25 August 2021. A total of 1,818 publications were identified, of which 29 were deemed eligible for inclusion that could be used to perform meta-analysis based on at least three data sources to assess whether the morbidity associated with neoplastic and non-neoplastic diseases can be attributed to SNPs in CHRNA genes. To further evaluate the authenticity of cumulative evidence proving significant associations, the present study covered the Venice criteria and false-positive report probability tests. Through the Encyclopedia of DNA Elements (ENCODE) project, we created functional annotations for strong associations.ResultsMeta-analyses were done for nine genetic variants with two diseases {chronic obstructive pulmonary disease (COPD) and lung cancer (LC)}that had at least three data sources. Interestingly, eight polymorphisms were significantly related to changes in the susceptibility COPD and LC (p &lt; 0.05). Of these, strong evidence was assigned to six variants (28 significant associations): CHRNA3 rs1051730, CHRNA3 rs6495309, and CHRNA5 rs16969968 with COPD risk, and CHRNA3 rs1051730, CHRNA3 rs578776, CHRNA3 rs6495309, CHRNA3 rs938682, CHRNA5 rs16969968, and CHRNA5 rs588765 with LC risk; moderate evidence was assigned to five SNPs (12 total associations) with LC or COPD risk. Data from ENCODE and other public databases showed that SNPs with strong evidence may be located in presumptive functional regions.ConclusionsOur study summarized comprehensive evidence showing that common mutations in CHRNA genes are strongly related to LC and COPD risk. The study also elucidated the vital function of CHRNA genes in genetic predispositions to human diseases.