Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

Circulating tumor DNA (ctDNA) in peripheral blood has become a promising noninvasive biomarker. However, the diagnostic potential of Wnt/β-catenin signaling pathway-related ctDNA for liver cancer is controversial. Here, we aimed to access the diagnostic potential and clinicopathological features of Wnt/β-catenin signaling pathway-related ctDNA in liver cancer and provide data support for its clinical diagnosis and treatment.

In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence.

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.

The tumorigenesis of lung cancer is complicated, and genetic factor may have the role in the malignant transformation of lung cells. IL-10 gene polymorphisms have been evaluated for their potential roles in lung cancer. However, those studies results are controversial. To clarify the effects of IL-10 rs1800871, rs1800872 and rs1800896 polymorphisms on the risk of lung cancer, a meta-analysis was performed with eligible individual studies.

Breast cancer is one of the most common cancers in the world and leading cause of cancer-related death among women. Several studies indicated that Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) may be associated with breast cancer risk. However, this association remains ambiguous. Thus, we performed a meta-analysis to provide more precise conclusion on this issue. A comprehensive search in PubMed, Google Scholar and ISI Web of Science was performed to select all relevant studies. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were applied to assess the strength of the relationships. A total of 17 studies with 5694 breast cancer cases and 6450 healthy subjects were identified. The pooled data revealed that XRCC2 Arg188His polymorphism was marginally with susceptibility to breast cancer globally under the heterozygote contrast (OR = 0.929, 95% CI = 0.873-0.987, p=0.018). Moreover, subgroup analysis by ethnicity revealed that this polymorphism was associated with breast cancer risk among Caucasians. On the whole, the present study demonstrates that the XRCC2 Arg188His polymorphism may contribute to an increased risk of breast cancer.

Poly (ADP-ribose) polymerase inhibitors (PARPi) represent an option in selected cases of metastatic castration-resistant prostate cancer (mCRPC). The aim of the present systematic review and meta-analysis is to evaluate the efficacy and safety of approved (Olaparib, Rucaparib) and investigational (Talazoparib, Niraparib, Veliparib) PARPi in mCRPC patients. Three databases were queried for studies analyzing oncological outcomes and adverse events of mCRPC patients receiving PARPi. Primary outcome was a PSA decline ≥ 50% from baseline. Secondary outcomes were objective response rate, progression-free survival (PFS), radiological PFS, overall survival (OS), conversion of circulating tumor cell count, and time to PSA progression. The number and rate of any grade adverse events (AEs), grade ≥ 3 AEs, and most common grade ≥ 3 AEs were registered. A subanalysis of outcomes per mutation type, prospective trials, and studies adopting combination therapies was performed. Overall, 31 studies were included in this systematic review, 28 of which are available for meta-analysis. The most frequently investigated drug was Olaparib. The most frequent mutation was BRCA2. A PSA decline rate of 43% (95% CI 0.32-0.54) was observed in the overall population. Mean OS was 15.9 (95% CI 12.9-19.0) months. In BRCA2 patients, PSA decline rate was 66% (95% CI 0.57-0.7) and OS 23.4 months (95% CI 22.8-24.1). Half of the patients suffered from grade 3 and 4 AEs (0.50 [95% CI 0.39-0.60]). Most common AEs were hematological, the most frequent being anemia (21.5%). PARP inhibitors represent a viable option for mCRPC patients. Current evidence suggests an increased effectiveness in homologous recombination repair (HRR) gene mutation carriers, especially BRCA2.

Non-small cell lung cancers (NSCLC) harboring Human Epidermal Growth Factor Receptor 2 (HER2) mutations represent a distinct subset with unique therapeutic challenges. Although immune checkpoint inhibitors (ICIs) have been transformative in lung cancer treatment, the efficacy of ICIs in HER2-mutated NSCLC remains to be established.

The objective of this meta-analysis is to evaluate the association between LncRNA MALAT1 and the clinicopathological characteristics and prognosis in patients with bladder cancer. Related studies were searched from Pubmed, Embase, Cochrane Library, CNKI and Web of Science up to Sep 1, 2021. Basic characteristic and prognostic data were extracted from the included studies. We synthesized and compared primary outcomes such as overall survival. Based on the cut-off value, sample size, and follow-up time, subgroup analysis was conducted. We calculated the combined hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) to assess the relationship between LncRNA MALAT1 and prognosis clinicopathological features of bladder cancer patients. Seven studies with 822 patients were included in this meta-analysis. The results showed that the high lncRNA MALAT1 was significantly related to poor overall survival (HR = 2.34, 95% CI:1.61-3.38; P<0.001) in bladder cancer patients. Furthermore, a high level of LNCRNA MALAT1 is associated with lymph node metastasis (LNM) (OR = 1.82, 95% CI 1.32-2.52, P <0.001) in bladder cancer. The results of sensitivity analysis showed the stabilization and reliability of results in this Meta-analysis. In conclusion, elevated LncRNA MALAT1 is associated with a poor prognosis and a higher risk of LNM in patients with bladder cancer. LncRNA MALAT1 could be identified as a biomarker with a potential prognostic value in bladder cancer.

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.

Head and neck cancer (HNC) is a prevalent and complex group of malignancies with increasing incidence globally. Alcohol dehydrogenases (ADHs) play a crucial role in alcohol metabolism, and their polymorphisms have been linked to HNC risk. This systematic review and meta-analysis aims to evaluate the association between ADH polymorphisms and susceptibility to HNCs, incorporating additional analyses and adding more studies to increase power and accuracy of the results.

Environmental pollutants known as polycyclic aromatic hydrocarbons (PAHs) are produced through the incomplete combustion of organic material. While PAHs have been investigated as genotoxicants, they can also operate through nongenotoxic pathways in estrogen-dependent malignancies, such as breast, cervical and ovarian cancer. However, whether PAHs induce colorectal cancer (CRC) risk through estrogenic effects is still illusive. Here, we systematically investigated the abnormal expression and activation of estrogen receptor beta (ERβ) regulated by PAHs in CRC as well as the underlying mechanisms of ERβ-mediated CRC risk. Based on the 300 plasma samples from CRC patients and healthy controls detected by GC-MS/MS, we found that the plasma concentrations of benzo[a]pyrene (BaP) were significantly higher in CRC cases than in healthy controls, with significant estrogenic effects. Moreover, histone deacetylase 2 (HDAC2)-induced deacetylation of the promoter decreases ERβ expression, which is associated with poor overall survival and advanced tumor stage. The study also revealed that BaP and estradiol (E2) had different carcinogenic effects, with BaP promoting cell proliferation and inhibiting apoptosis, while E2 had the opposite effects. Additionally, this study mapped ERβ genomic binding regions by performing ChIP-seq and ATAC-seq and identified genetic variants of rs1411680 and its high linkage disequilibrium SNP rs6477937, which were significantly associated with CRC risk through meta-analysis of two independent Chinese population genome-wide association studies comprising 2,248 cases and 3,173 controls and then validation in a large-scale European population. By integrating data from functional genomics, we validated the regulatory effect of rs6477937 as an ERβ binding-disrupting SNP that mediated allele-specific expression of LINC02977 in a long-range chromosomal interaction manner, which was found to be highly expressed in CRC tissues. Overall, this study suggests that the different active effects on ERβ by PAHs and endogenous E2 may play a crucial role in the development and progression of CRC and highlights the potential of targeting ERβ and its downstream targets for CRC prevention and treatment.

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs.

Estrogen receptor (ER) is a molecular marker and target for diagnosing and treating breast cancer (BC). ER-α36, a novel estrogen receptor subtype, involved in the proliferation, differentiation, metastasis, and invasion of tumor cells. It is closely linked to the progression of various cancers. Therefore, studying ER is of high significance in treating BC. In this study, we will investigate the changes in the expression level of ER-α36 in patients with BC treated by chemotherapy through meta-analysis, so as to evaluate the clinical value of ER-α36 in the prognosis of BC treated by chemotherapy. English databases such as PubMed, Web of Science, Embase, and The Cochrane Library were searched to retrieve the articles published from the establishment of the database to April 2023. The keywords included chemotherapy, neoadjuvant chemotherapy, breast cancer, estrogen receptor alpha, and ER-α36. Five suitable studies, encompassing 636 patients, were ultimately selected. The meta-analysis results revealed that, following the chemotherapy, the analysis of ER-α36 positive cases yielded an Odds Ratio (OR) of 0.42, a 95% confidence interval (CI) of 0.28-0.64 (Z = 4.00, P < 0.0001). Additionally, the analysis of cases exhibiting remission in BC demonstrated an OR of 2.22 (95% CI = 1.40-3.50, Z = 3.40, P = 0.0007). Compared to patients receiving single chemotherapy agents or those untreated with chemotherapy, the combined use of multiple chemotherapy drugs can significantly reduce the levels of ER-α36 in BC patients, enhancing the remission rate of BC. ER-α36 can serve as a critical indicator for assessing the prognosis of BC following chemotherapy.

Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges.

Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs.

POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior.

The cancer biomarker field has been an object of thorough investigation in the last decades. Despite this, colorectal cancer (CRC) heterogeneity makes it challenging to identify and validate effective prognostic biomarkers for patient classification according to outcome and treatment response. Although a massive amount of proteomics data has been deposited in public data repositories, this rich source of information is vastly underused. Here, we attempted to reuse public proteomics datasets with two main objectives: i) to generate hypotheses (detection of biomarkers) for their posterior/downstream validation, and (ii) to validate, using an orthogonal approach, a previously described biomarker panel. Twelve CRC public proteomics datasets (mostly from the PRIDE database) were re-analysed and integrated to create a landscape of protein expression. Samples from both solid and liquid biopsies were included in the reanalysis. Integrating this data with survival annotation data, we have validated in silico a six-gene signature for CRC classification at the protein level, and identified five new blood-detectable biomarkers (CD14, PPIA, MRC2, PRDX1, and TXNDC5) associated with CRC prognosis. The prognostic value of these blood-derived proteins was confirmed using additional public datasets, supporting their potential clinical value. As a conclusion, this proof-of-the-concept study demonstrates the value of re-using public proteomics datasets as the basis to create a useful resource for biomarker discovery and validation. The protein expression data has been made available in the public resource Expression Atlas.

Several recent studies have reported the increasing application of preoperative circulating tumor DNA (ctDNA) as a biomarker of tumor burden for guiding potential postoperative treatment strategies.