Exploratory Study of a New Technique of Pixelated Chromoendoscopy in the Diagnosis of Early Esophageal Cancer.

BACKGROUND: Chromoendoscopy is an effective method for early screening of esophageal cancer, but diagnosis can depend on subjective judgment. The study aimed to explore a new technique of pixelated chromoendoscopy in the diagnosis of early esophageal cancer. PATIENTS AND METHODS: The study included patients with symptoms of esophageal cancer who attended Jiangyin People's Hospital between January 2015 and July 2021. Chromoendoscopy was performed on each patient. The images then underwent digital analysis; the lesion area (the sensitive region) was pixelated by dividing it into the smallest image unit and the red, green, and blue color components. The diagnostic performance of pixelated chromoendoscopy was evaluated by calculating the area under the receiver operating characteristic. RESULTS: The study finally enrolled 86 patients (aged 51.34 ± 5.82 y), including 54 males and 32 females. Pathologic diagnosis identified 54 cases in the cancer group and 32 cases in the non-cancer group. Traditional judgment had a diagnostic sensitivity of 70.73% and specificity was 75.00%. Pixelated chromoendoscopy sensitivity was 80.49%, and specificity was 83.33%. The area under the receiver operating characteristic was 0.814, at a cutoff value of 0.625, indicating a good prediction effect. CONCLUSIONS: These results showed that pixelated chromoendoscopy might improve the rate of esophageal cancer diagnoses from early screening.

Comprehensive plasma metabolomics and lipidomics of benign and malignant solitary pulmonary nodules.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates. OBJECTIVE: We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics. METHODS: In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GC‒MS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LC‒MS) were used to analyze the samples for untargeted metabolomics and lipidomics. RESULTS AND CONCLUSION: GC‒MS-based metabolomics revealed 1336 metabolic features, while LC‒MS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.

Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

Pralsetinib treatment for multiple RET fusions in lung adenocarcinoma: a case report.

Despite recent advances in treatments and knowledge of biomarkers, patients with metastatic lung cancer have a 5-year survival rate of 5%. Rearranged during transfection (RET) fusions occur in 1% to 2% of lung cancer patients. Pralsetinib has been used to treat non-small cell lung cancer with a single RET fusion; however, there have been no reports regarding its use in patients with multiple RET fusions. Genetic mutations in tumor tissues were tested using Amplification Refractory Mutation System-PCR and next-generation sequencing (NGS). Pleural fluids obtained from a male patient with non-small cell lung cancer were also used to detect genetic aberrations by NGS. Pleural fluid-based NGS revealed three RET rearrangements: CCDC6-RET (C2:R12), RET-NRG3 (R11:N3), and CCDC6-RET (C1:R12). All three rearrangements were targeted by pralsetinib, a RET fusion inhibitor. Pralsetinib drastically improved the patient's condition within 4 days, and a partial response was achieved 1 week after pralsetinib was administered. We report for the first time the important clinical observation of a patient with multiple RET fusions who was effectively treated with pralsetinib.

Potential value of tripartite motif-containing 59 as a biomarker for predicting the prognosis of patients with lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: In recent years, related studies have revealed that tripartite motif-containing 59 (TRIM59) is related to the prognosis of lung cancer. However, these results have not been proved by any evidence. Therefore, this study evaluated the relationship between TRIM59 and the prognosis of lung cancer by carrying out meta-analysis. In addition, we explored the mechanism and related pathways of TRIM59 in lung cancer through bioinformatics analysis. METHODS: Comprehensive literature search was performed in China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang, Web of Science, PubMed, and EMBASE databases, and eligible studies were obtained based on the inclusion and exclusion criteria. The pooled hazard ratios and odds ratios were applied to assess the clinical value of TRIM59 expression for overall survival and clinicopathological features. Meanwhile, meta-analysis was conducted on the Stata 16.0. The mRNA expression level of TRIM59 in lung cancer was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Set Enrichment Analysis (GSEA) was used to predict the signaling pathways that TRIM59 might be involved in. The correlation between the expression level of TRIM59 in lung cancer and the abundance of immune cell invasion was analyzed by TIMER database. The survival analysis was verified by Kaplan-Meier Plotter database. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: In this study, the application of meta-analysis and bioinformatics analysis will provide evidence support for the study on the prognosis and mechanism of TRIM59 in lung cancer.

Nanotoxic Effects of Silver Nanoparticles on Normal HEK-293 Cells in Comparison to Cancerous HeLa Cell Line.

PURPOSE: Biomimetic approaches for the synthesis of silver nanoparticles (AgNPs) had created a substantial impression among the research community that focuses on nano-bio interactions. In this study, an eco-friendly method using Rhizophora apiculata aqueous leaf extract as a reductant-rich hydrosol was followed to synthesize AgNPs and test its cytotoxicity. METHODS: To optimise the parameters for the synthesis of AgNPs, central composite design based on response surface methodology was used. The particles synthesized at a nano-scale were characterized in our previously published report. The present report further characterizes the nanoparticles by X-ray diffraction, SEM and TEM at varying sites and magnifications. The characterized AgNPs were tested for their cytotoxic effects on HEK-293 and HeLa cells. RESULTS: The cytotoxicity on the cell lines was dose-dependent. At a concentration of 2.5 µL/mL of the AgNPs-containing hydrosol, 100% inhibition of HEK-293 cells and 75% inhibition of the HeLa cells were observed. The IC50 value for AgNPs on HEK-293 was 0.622 µL/mL (12.135 ng), whereas, for HeLa cells, it was 1.98 µL/mL (38.629 ng). CONCLUSION: The nanoparticles were three-fold toxic towards the HEK-293 cells in comparison to the HeLa cells. Therefore, the therapeutic index is low for R. apiculata derived AgNPs on HeLa cells when tested in comparison with the HEK-293 cells. The nanotoxicity profile of the synthesized AgNPs seems more prominent than the nanotherapeutic index. According to our knowledge, this is the first-ever report on the optimization of synthesis of AgNPs using response surface methodology and identifying the therapeutic index of mangrove leaf-derived AgNPs.

LINC00565 promotes the progression of colorectal cancer by upregulating EZH2.

The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). The relative levels of LINC00565 and EZH2 in CRC tissues, based on their Tumor-Node-Metastasis stage and tumor size, were detected by reverse transcription-quantitative polymerase chain reaction. The diagnostic value of LINC00565 in CRC was assessed by depicting receiver operating characteristic curves. Pearson's correlation test was applied to analyze the expression correlation between LINC00565 and EZH2 in CRC tissues. The transfection efficacy of three LINC00565 small interfering RNAs was examined in CRC HCT116 and SW480 cell lines. After knockdown of LINC00565, the proliferative and migratory abilities of CRC cells were detected by Cell Counting Kit-8 and Transwell assays, respectively. The subcellular distribution of LINC00565 was analyzed, and the interaction between LINC00565 and EZH2 was determined by RNA immunoprecipitation. Finally, co-regulation of LINC00565 and EZH2 on CRC cell functions was explored by performing rescue experiments. Results showed that LINC00565 was upregulated in CRC tissues, especially in patients with stage III+IV and in those with large tumor sizes, suggesting its diagnostic value in CRC. EZH2 was also upregulated in CRC tissues, showing a positive correlation with LINC00565. LINC00565 was mainly expressed in the cytoplasm and was found to bind with EZH2. Validation was performed by overexpressing EZH2, which abolished the role of silenced LINC00565 in regulating proliferative and migratory abilities in CRC. Therefore, the upregulation of LINC00565 in CRC tissues was found to stimulate the aggravation of CRC by upregulating EZH2.

[Application of metabonomics examination in differential diagnosis of non-small cell lung cancer (NSCLC)].

Objective To explore the preliminary application of metabonomics in the qualitative diagnosis of non-small cell lung cancer (NSCLC). Methods According to the pathological type, 201 patients with NSCLC were divided into squamous cell carcinoma (SCC) group (n=71) and adenocarcinoma (AC) group (n=130). Immunohistochemistry was used to detect the expression of ki67, cytokeratin 5/6 (CK5/6) and CK7. Ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to detect serum metabolomics. Results SCC group showed typical SCC structure; ki67 proliferation index was 21.9%; CK5/6 expression was positive; CK7 expression was negative or weakly positive. The typical adenoid structure was found in the AC group; the proliferation index of ki67 was 17.6%; CK7 was positive; and CK5/6 was negative or weakly positive. UPLC-Q/TOF-MS screened 28 different metabolites, of which 6 were the most significant ones: L-leucine, carnitine, C16 sphinganine, 13, 16, 19-docosatrienoic acie (DA), LysoPE (18:2/0:0), PC (20:4/P-16:0). These metabolites had good diagnostic value, among which L-Leucine had the highest specificity and LysoPE had the highest sensitivity. Conclusion Metabolomic analysis of lung SCC and AC provides a new index for the differential diagnosis of NSCLC.

Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer Progression through Inhibiting NF-κB Signaling Pathway.

BACKGROUND/AIMS: Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. Dopamine receptor D2 (DRD2) has multiple roles in clinical progression of NSCLC and functional maintenance of cancer cells. However, little is known about the molecular mechanism. Here, we clarified whether DRD2 inhibits lung cancer progression and identified the underlying downstream signaling. METHODS: DRD2 mRNA and protein levels were detected in clinical specimens by qRT-PCR and immunohistochemistry, respectively. MTT and colony formation assays were applied to analyze cell proliferation. The underlying molecular mechanism was identified by dual luciferase, western blot, qRT-PCR, cAMP detection, immunoprecipitation, and chromatin immunoprecipitation assays. A murine NSCLC model was used to clarify the role of DRD2 in tumor cell proliferation. RESULTS: We found that DRD2 ablated tumor cell growth. DRD2 expression in NSCLC tissues was lower than in adjacent normal lung tissues. Moreover, DRD2 mRNA and protein levels in NSCLC were negatively correlated with the tumor size, TNM status, and patient overall survival. In vitro experiments showed that disruption of DRD2 promoted the proliferation of NSCLC cell lines A549 and SK-MES-1 by inhibiting the NF-κB signaling pathway. Furthermore, DRD2 overexpression not only blocked lipopolysaccharide-induced A549 and SK-MES-1 cell proliferation and growth, but also inhibited the tumorigenesis in murine xenograft models. CONCLUSION: These results indicate that DRD2 may be a potential therapeutic target for lung cancer patients with high DRD2 expression by ablating the NF-κB signaling pathway.

Associations between polymorphisms of long non-coding RNA MEG3 and risk of colorectal cancer in Chinese.

Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), is involved in cancer development and metastasis. The objective of the present study was to evaluate whether common single nucleotide polymorphisms (SNPs) in MEG3 could be related with colorectal cancer risk in Chinese. We genotyped six tagSNPs of MEG3 in a colorectal cancer case-control study including 518 cases and 527 control subjects. Multivariate logistic regression analysis was applied to calculate adjusted odds ratios (ORs). We found that MEG3 rs7158663 AA genotype, but not GA genotype, had significant increased colorectal cancer risk, compared with GG genotype (OR = 1.96 and P = 0.006 for AA versus GG, and OR = 1.20 and P = 0.171 for GA versus GG). Further stratified analysis indicated that the increased risk was significantly correlated with individuals with age ≤ 60 and family history of cancer. However, there was no significant association between rs7158663 and colorectal tumor site and stage (P = 0.842 for tumor site, and P = 0.601 for tumor stage). These results demonstrate that genetic variants in MEG3 may contribute to the development and risk of colorectal cancer. Further studies are required to confirm these findings.

Thalidomide Combined with Chemotherapy in Treating Patients with Advanced Colorectal Cancer.

OBJECTIVE: To assess the safety and effectiveness of thalidomide (produced by CHANGZHOU PHARMACEUTICAL FACTORY CO.LTD) combined with chemotherapy in treating patients with advanced colorectal cancer. METHOD: A consecutive cohort of pretreated patients with advanced colorectal cancer were treated with thalidomide combined with chemotherapy. And chemotherapy for patients with advanced colorectal cancer were administered according to the condition of patients. Thalidomide was orally administered at a dosage of 50mg/day to 150 mg/day before sleeping for at least 14 days. After at least 14 days of treatment, safety and side effects were evaluated. RESULTS: There were 12 female and 3 male patients with advanced cancer recruited into this study, including 9 patients with colon, 6 patients with rectal cancer. The median age of patients was 57(41- 82) years. Partial response was observed in 2 patients (2/15), and stable disease in 3 patients(3/15). Incidences of Grade 1 to 2 myelosuppression was observed in 1/15 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 1/15 patients. Adverse effects on the gastrointestinal tract were documented in 1/15 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. CONCLUSIONS: Thalidomide combined with chemotherapy was safe and mildly effective in treating patients with advanced colorectal cancer. However, further study should be conducted to clarify the effectiveness of this combination.

Sphingosine kinase-1 activation causes acquired resistance against Sunitinib in renal cell carcinoma cells.

Multi-target tyrosine kinase inhibitor Sunitinib has been widely used in cancer treatment, including metastatic renal cell carcinoma. However, most patients who initially benefit from Sunitinib develop resistance with extended usage of Sunitinib, which is referred to as "acquired resistance". The molecular mechanisms contributing to this acquired resistance remain poorly understood. In this present study, we established Sunitinib-resistant cell lines from human renal cell lines (786-O, A498, ACHN and CAKI1) by continuous treatment with Sunitinib to explore the molecular mechanism leading to Sunitinib resistance. We found that PDGFR-ß expression in cell seems to be a protective factor against Sunitinib resistance formation. In addition, we found that both SK1 and ERK were activated in Sunitinib-resistance cell lines and SK1 and ERK inhibitors could resensitize Sunitinib-resistant cell lines. In conclusion, our observations suggest that SK1 and ERK activation is a feature of resistant cell lines, which serves as an alternative pathway evading anti-tumor activity of Sunitinib.

Association of the SNP rs1800925(C/T) in the interleukin-13 gene promoter with pulmonary function in Chinese Han patients with idiopathic pulmonary fibrosis.

The present report studied potential association of the rs1800925(C/T) single nucleotide polymorphism (SNP) of the Interleukin (IL)-13 gene promoter with idiopathic pulmonary fibrosis (IPF) in patients of Chinese Han ethnicity. Seventy patients with IPF were enrolled and divided into three subgroups: group A (61-79 % pred. DLCO; n = 22), group B (51-60% pred. DLCO; n = 20), and group C (≤50% pred. DLCO; n = 28). Control group consisted of 80 healthy individuals of Chinese Han ethnicity. The SNP rs1800925(C/T) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The IL-13 CC genotype was present in 28/70 (40.0%), homozygous TT in 6/70 (8.6%) and heterozygous CT in 36/70 (51.4%) patients with IPF. In control group, these genotypes were present in 30/80 (37.5%), 11/80 (13.75%), 39/80 (48.75%), respectively, indicating that the distribution of the above three genotypes was not significantly different between patients with IPF and healthy controls. When the patients were stratified according to their DLCO and DLCO/VA, the frequencies of genotypes CT and TT in the groups A, B, and C were, respectively, 40.9% (9/22), 50% (10/20), and 82.1% (23/28). Thus, significant differences in the distribution of alleles at -1112 region of IL-13 gene were observed among the study groups A, B, and C, with the highest frequency in group C (p < 0.05). In conclusion, the rs1800925 T allele of the IL-13 gene is associated with worse pulmonary function in patients with IPF of Chinese Han ethnicity.

[Curative effect of 3D-CRT combined with gemcitabine concurrently with addition of Kanglaite Injection in treatment of locally advanced pancreatic].

OBJECTIVE: To explore the efficacy of concurrent chemoradiotherapy combined with Kanglaite Injection (KI) for locally advanced pancreatic carcinoma patients. METHODS: Totally 50 patients unsuitable for surgery were randomly assigned to the treatment group and the control group, 25 in each group. Patients in the control group were treated with gemcitabine and concurrent 3D-CRT, while those in the treatment group were also treated with intravenous injection of KI (at 100 mL/d) for 21 successive days, 28 days as one cycle, two cycles with one week interval. The short-term curative effect, the survival time, the improvement of symptoms, the tumor markers, and adverse reactions were respectively observed for two years. RESULTS: The short-term curative effective rate (CR + PR) was 52.17% (12/23), and the disease control rate (CR + PR + SD) was 95.65% (22/23) in the treatment group. The short-term curative effective rate (CR + PR) was 41.67% (10/24), and the disease control rate (CR + PR + SD) was 87.50% (21/24) in the control group. There was no statistical difference between the two groups (P > 0.05). The 2-year survival rate was 34.78% (8/23) in the treatment group, better than that in the control group (25.00%, 6/24). The median survival time was 17.2 months in the treatment group and 12.4 months in the control group with statistical difference (P < 0.05). The response rate of pain relief and weight gain were 75.00% and 82.61% in the treatment group respectively, and they were 50.00% and 54.67% in the control group respectively, showing statistical difference between the two groups (P < 0.05). After treatment, the levels of CA19-9 (U/mL) and CEA (ng/mL) were respectively reduced to 118. 00 +/- 78.89 and 7.41 +/- 2.37 respectively in the treatment group, showing statistical difference when compared with those of the control group (being 216.00 +/- 153.23 and 12.25 +/- 7.53 respectively, P < 0.05). CONCLUSION: The concurrent chemoradiotherapy com- bined with KI for locally advanced pancreatic carcinoma patients obtained better results.

Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

BACKGROUND: Salidroside [2-(4-hydroxyphenyl)ethyl-ß-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated. OBJECTIVE: The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin. METHODS: Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n = 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2. RESULTS: A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p < 0.05) and 400 mg/m2 (1.68 ± 0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside. CONCLUSION: Salidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis.

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case-control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy-Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16-2.33; GA versus GG, OR = 1.42, 95% CI = 1.18-1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21-1.72). Furthermore, Egger's test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.