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Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

BACKGROUND Colon adenocarcinoma (COAD) is one of the most common and fatal malignant tumors, which increases the difficulty of prognostic predictions. Thus, new biomarkers for the diagnosis and prognosis of COAD should be explored. Ferroptosis is a recently identified programmed cell death process that has the characteristics of iron-dependent lipid peroxide accumulation. However, the predictive value of ferroptosis-related genes (FRGs) for COAD still needs to be further clarified. AIM To identify some critical FRGs and construct a COAD patient prognostic signature for clinical utilization. METHODS The Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus databases were the data sources for mRNA expression and corresponding COAD patient clinical information. Differentially expressed FRGs were recognized using R and Perl software. We constructed a multi-FRG signature of the TCGA-COAD cohort by performing a univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis. COAD patients from the Gene Expression Omnibus cohort were utilized for verification. RESULTS Our research showed that most of the FRGs (85%) were differentially expressed between the corresponding adjacent normal tissues and cancer tissues in the TCGA-COAD cohort. Seven FRGs were related to overall survival (OS) in the univariate Cox analysis (all P < 0.05). A model with five FRGs ( AKR1C1, AKR1C3, ALOX12, CRYAB, and FDFT1 ) was constructed to divide patients into high- and low-risk groups. The OS of patients in the high-risk group was significantly lower than that of the low-risk group (all P < 0.01 in the TCGA and Gene Expression Omnibus cohorts). The risk score was an independent prognosticator of OS in the multivariate Cox analysis (hazard ratio > 1, P < 0.01). The predictive capacity of the model was verified by a receiver operating characteristic curve analysis. In addition, a nomogram based on the expression of five hub FRGs and risk score can precisely predict the OS of individual COAD cancer patients. Immune correlation analysis and functional enrichment analysis results revealed that immunology-related pathways were abundant, and the immune states of the high-risk group and the low-risk group were different. CONCLUSION In conclusion, a novel five FRG model can be utilized for predicting prognosis in COAD. Targeting ferroptosis may be a treatment option for COAD.

Background Duodenal carcinoma is the third cause of mortality in familial adenomatous polyposis (FAP) patients. The molecular mechanism by which FAP triggers and regulates duodenal carcinoma development was seldom studied so far. Objective The present study sought to use the bioinformatics approaches to provide novel insights into the molecular mechanism of FAP developing into duodenal carcinoma. Methods Based on GSE111156 dataset, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify differentially expressed genes (DEGs) and key gene modules, respectively. The functional enrichment analysis was conducted R package “clusterProfiler” and biological functions and pathways related to the immune system were further identified. Results Between adenoma tissue samples from FAP patients with and without duodenal carcinoma, 13 up-regulated genes including MIR4747, THBS1, and RNU6_62 and 113 down-regulated genes including AKR1B10, AGAP9 and AKR1C3 were identified. These DEGs were mainly involved in terpnoid metabolism. In WGCNA analysis, the blue module associated with duodenal carcinoma in FAP contained 5393 genes including 11 hub genes and was mainly related to the regulation of neuron projection development. In tissues from FAP patients with duodenal carcinoma, 32 up-regulated genes including INHBA, COL3A1, and COL1A1 and 18 down-regulated genes including MT1H, KIAA1324, and HMGCS2 were screened between adenocarcinoma and normal tissues and were also significantly related to terpnoid metabolism. Between adenocarcinoma and adenoma tissues, we screened 171 up-regulated genes including CEACAM5, SLC2A1 and PKMRNU6_62 and 238 downregulated genes including RBP2, GSTA5 and SST, which were mainly involved in extracellular matrix organization. WGCNA revealed that the darkorange module associated with adenocarcinoma contained 554 genes including 19 hub genes and was involved in extracellular matrix organization and focal adhesion. Further identification of immune related processes showed that leukocyte migration was the process mostly involved in the transition of normal tissue into adenoma while neutrophil-mediated immunity was the most dysregulated in adenocarcinoma. Conclusion The present study preliminary uncovered the mechanism behind initiation and progression in duodenal carcinoma in FAP, and provided some scientific information for exploring novel therapeutic strategies for FAP patients with duodenal carcinoma.

The most prevalent type of intestinal polyposis, colorectal adenomatous polyposis (CAP), is regarded as a precancerous lesion of colorectal cancer with obvious genetic characteristics. Early screening and intervention can significantly improve patients’ survival and prognosis. The adenomatous polyposis coli ( APC ) mutation is believed to be the primary cause of CAP. There is, however, a subset of CAP with undetectable pathogenic mutations in APC , known as APC (-)/CAP. The genetic predisposition to APC (-)/CAP has largely been associated with germline mutations in some susceptible genes, including the human mutY homologue (MUTYH) gene and the Nth-like DNA glycosylase 1 (NTHL1) gene, and DNA mismatch repair (MMR) can cause autosomal recessive APC (-)/CAP. Furthermore, autosomal dominant APC (-)/CAP could occur as a result of DNA polymerase epsilon ( POLE )/DNA polymerase delta 1 ( POLD1 ), axis inhibition protein 2 ( AXIN2 ), and dual oxidase 2 ( DUOX2 ) mutations. The clinical phenotypes of these pathogenic mutations vary greatly depending on their genetic characteristics. Therefore, in this study, we present a comprehensive review of the association between autosomal recessive and dominant APC (-)/CAP genotypes and clinical phenotypes and conclude that APC (-)/CAP is a disease caused by multiple genes with different phenotypes and interaction exists in the pathogenic genes.