To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.

Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic meta-analysis to evaluate the diagnostic value of noncoding salivary RNAs in pancreatic cancer diagnosis.

This study was undertaken to evaluate the prognostic significance of circulating tumour DNA (ctDNA) detection at different time periods in resectable non-small cell lung cancer (NSCLC). A comprehensive search strategy was conducted through the electronic platforms published up to June 2022. In total, 7 studies with 1138 patients were included. Patients with positive ctDNA have an increased risk of recurrence and mortality. The association between risk of recurrence and detectable ctDNA after surgery 3 days-2 weeks and 1-3 months was stronger than detected at 1 week before surgery. The predictive value of longitudinal detection ctDNA for recurrence and mortality was not stronger than at other time periods. In conclusion, ctDNA is a promising biomarker for predictive recurrence and survival in resectable NSCLC patients. The ctDNA detection after surgery 3 days-2 weeks with more reliably and feasible in identifying resectable NSCLC patients at high risk for recurrence.

Several studies have inspected the relationship between rs735482 polymorphism and the risk of some human cancers, but the findings remain controversial. We designed this meta-analysis to validate the association between rs735482 polymorphism and cancer risk. All articles were published before September 1, 2018 and searched in Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, WangFang, and Chinese BioMedical databases, STATA 12.0 software was used for statistical analysis, which provides reasonable data and technical support for this article. A total of 10 studies were included in the meta-analysis, including 2652 cancer cases and 3536 rs735482 polymorphic controls. Data were directly extracted from these studies and odds ratios with 95% confidence intervals were computed to estimate the strength of the association. By pooling all eligible studies, the rs735482 polymorphism showed no significant association with susceptibility of several cancers in all the five genetic models (the allelic model: OR = 1.019, 95% CI: 0.916-1.134, P = .731). In addition, another adjusted OR data showed a significant increased risk between the rs735482 and susceptibility of several cancers (the codominant model BB vs AA: OR = 1.353, 95% CI: 1.033-1.774, P = .028) and the stratification analysis by ethnicity indicated the rs735482 is associated with an increased risk of cancer in Chinese group (BB vs AA, OR = 1.391, 95% CI = 1.054-1.837, P = .020; AB+BB vs AA OR = 1.253, 95% CI = 1.011-1.551, P = .039). However, the ERCC1 rs735482 is associated with a decreased risk of cancer in Italian group (AB vs AA, OR = 0.600, 95% CI = 0.402-0.859, P = .012; AB + BB vs AA, OR = 0.620, 95% CI = 0.424-0.908, P = .014). The results of this meta-analysis do not support the association between rs735482 polymorphism and cancer risk. But stratified analysis showed that rs735482 significantly increased the risk of cancer in Chinese while decreased the risk of cancer in Italian. Because of the limited number of samples, larger and well-designed researches are needed to estimate this association in detail.

There are conflicting opinions on whether miR-486 could be used for cancer diagnosis and prognosis. Therefore, this present study investigated the potential effect of miR-486 on lung cancer diagnosis and prognosis.

Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) exhibits unusual geographic restriction despite ubiquitous lifelong infection. Screening programs can detect most NPC cases at an early stage, but existing EBV diagnostics are limited by false positives and low positive predictive value (PPV), leading to excess screening endoscopies, MRIs, and repeated testing. Recent EBV genome-wide association studies (GWAS) suggest that EBV BALF2 variants account for more than 80% of attributable NPC risk. We therefore hypothesized that high-risk BALF2 variants could be readily detected in plasma for once-lifetime screening triage.

Cervical cancer is the fourth commonest and the fourth leading cause of cancer death in females globally. The upregulated expression of microRNA-21 in cervical cancer has been investigated in numerous studies, yet given the inconsistency on some of the findings, a systematic review and meta-analysis is needed. Therefore, the aim of this systematic review and meta-analysis is to investigate the role in disease progression as well as the diagnostic and prognostic value of microRNA-21 in patients with cervical cancer.

Taxane-based chemotherapy regimens are used as first-line treatment for breast cancer. Neurotoxicity, mainly taxane-induced peripheral neuropathy (TIPN), remains the most important dose-limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random-effects gene meta-analyses and examined interstudy heterogeneity with meta-regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single-nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta-analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1-rs2032582, ABCB1-rs3213619, BCL6/-rs1903216, /CAND1-rs17781082, CYP1B1-rs1056836, CYP2C8-rs10509681, CYP2C8-rs11572080, EPHA5-rs7349683, EPHA6-rs301927, FZD3-rs7001034, GSTP1-rs1138272, TUBB2A-rs9501929, and XKR4-rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta-analysis. In conclusion, through systematic review and meta-analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.

Background: Signet ring cell carcinoma (SC) accounts for 1% of total colorectal cancer (CRC) cases and is associated with aggressive behaviors, such as lymphatic invasion and distant metastases, resulting in poor prognosis. To date, there is still a lack of consensus on the genetic etiology underpinning this cancer subtype. This study aimed to clarify the molecular associations of SC by using meta-analysis and a systematic review. Methods: PubMed, Embase, and Cochrane Library were searched for studies evaluating the KRAS, BRAF, P53 statuses, and microsatellite instability (MSI) in CRC patients with different histological subtypes, including SC. The diagnosis of SC is defined as the signet ring cells comprising ≥50 percent of the tumor mass. By dividing the studies into subgroups based on the composition of control groups, such as classic adenocarcinoma (AC; no SC components) and non-SC (including those with SC components < 50%), the relative risk (RR) of molecular alterations for SC in each study were pooled using a random-effects model. Two reviewers identified trials for inclusion, assessed quality, and extracted data independently. Results: Data from 29 studies consisting of 9366 patients were included in this analysis. SC was associated positively with MSI (RR 1.78, 95% CI 1.34 to 2.37; 95% CI 0.77 to 4.15; p = 0.0005), BRAF mutation (RR 1.99, 95% CI 1.21 to 3.26; 95%CI 0.68 to 5.82; p = 0.0146), and negatively with KRAS mutation (RR 0.48, 95% CI 0.29 to 0.78; 95% CI 0.09 to 2.49; p = 0.0062). No association was found between SC and P53 expression (RR 0.92, 95% CI 0.76 to 1.13; 95%CI 0.61 to 1.39; p = 0.3790). Moreover, it was associated negatively with P53 gene mutations (RR 0.92, 95% CI 0.77 to 1.09; 95% CI 0.46 to 1.82; p = 0.1568), and P53 protein (RR 0.93, 95% CI 0.58 to 1.49; 95% CI 0.40 to 2.17; p = 0.6885). Conclusions: The molecular etiology of SC may be associated with the BRAF and MSI pathways. Its features, such as the high frequency of BRAF mutation, could partly explain its less favorable outcomes and limited effects of traditional chemotherapy.

Although programmed cell death-ligand 1 (PD-L1) has been recognized as a potential marker in several cancers, the relationship between PD-L1 expression and survival in patients with salivary gland carcinoma (SGC) has remained unclear. We aimed to evaluate the association of PD-L1 expression with clinicopathological features and prognosis in SGC patients.

Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis.

A growing number of regimens have been approved as first-line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer. However, the optimal regimen has not been determined, especially for patients with different clinicopathological characteristics. Therefore, we performed this meta-analysis to compare the efficacy and safety of first-line treatments for patients with EGFR-mutated NSCLC based on clinicopathological characteristics, thereby providing evidence for individual patient clinical decision-making.

Observational studies provided conflicting results on the association between iron status and the risk of lung cancer. The aim of our study was to investigate the effect of genetically determined iron status on lung cancer risk using a mendelian randomization (MR) approach. Single-nucleotide polymorphisms for iron status were selected from a genome-wide meta-analysis of 48,972 subjects. Genetic association estimates for risk of lung cancer were derived from a Genome-Wide Association Study (GWAS) summary performed by the International Lung Cancer Consortium. The inverse-variance weighted method was used for the main analyses and sensitivity analyses. MR analysis demonstrated that increased genetically-predicted iron status did not causally increase risk of lung cancer. The odds ratios were 1.11 (95% CI, 0.92, 1.34; P = .26), 0.76 (95% CI, 0.52, 1.12; P = .17), 1.09 (95% CI, 0.86, 1.38; P = .47), and 0.91 (95% CI, 0.81, 1.02; P = .11) per 1 standard deviation increment of serum iron, ferritin, transferrin saturation, and transferrin levels, respectively. No observed indication of heterogeneity (P for Q > 0.05) or pleiotropy (P for intercept > 0.05) were found from the sensitivity analysis. The MR study indicated that genetic iron status was not causally associated with the risk of lung cancer, the causal relationship between iron status and lung cancer needs to be further elucidated by additional studies that strictly control for confounding factors.

Tumor mutation burden (TMB) has been reported to emerge as an independent biomarker of response to identify patients who would achieve benefit from immune checkpoint inhibitors. However, it still remains controversy that whether TMB can be a robust biomarker of response to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibition. We performed this meta-analysis to assess the relationship between TMB and the efficacy with PD-1/PD-L1 inhibition in advanced nonsmall cell lung cancer (NSCLC).

Inflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach.

Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.

Nucleolin (NCL) is a multifunctional protein expressed in the nucleus, cytoplasm, and cell membrane. Overexpression of NCL has a controversial role as a poor prognostic marker in cancers. In this study, a meta-analysis was performed to evaluate the prognostic value of NCL in different subcellular localizations (cytoplasmic (CyNCL) and nuclear (NuNCL)) across a range of cancers. PubMed was searched for relevant publications. Data were extracted and analyzed from 12 studies involving 1221 patients with eight cancer types. The results revealed high total NCL was significantly associated with poor overall survival (OS) (HR = 2.85 (1.94, 4.91), p < 0.00001, I2 = 59%) and short disease-free survival (DFS) (HR = 3.57 (2.76, 4.62), p < 0.00001, I2 = 2%). High CyNCL was significantly associated with poor OS (HR = 4.32 (3.01, 6.19), p < 0.00001, I2 = 0%) and short DFS (HR = 3.00 (2.17, 4.15), p < 0.00001, I2 = 0%). In contrast, high NuNCL correlated with increased patient OS (HR = 0.42 (0.20, 0.86), p = 0.02, I2 = 66%), with no significant correlation to DFS observed (HR = 0.46 (0.19, 1.14), p = 0.09, I2 = 57%). This study supports the role of subcellular NCL as a poor prognostic cancer biomarker.

Selecting the appropriate patient for further treatment after surgery and adjuvant chemotherapy (ACT) for colorectal cancer (CRC) can improve the patient's prognosis. Circulating tumour DNA (ctDNA) has the potential to predict recurrence and prognosis after CRC surgery and ACT, but the results are still inconclusive.

This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values.

The progesterone response of the nuclear progesterone receptor plays an important role in the female reproductive system. Changes in the function of the progesterone receptor gene may increase the risk of reproductive cancer. The present study performed a meta-analysis to examine whether the progesterone receptor gene PROGINS polymorphism was a susceptibility factor for female reproductive cancer.