Organophosphate esters in milk across thirteen countries from 2020 to 2023: Concentrations, sources, temporal trends and ToxPi priority to humans.

Recent increases in organophosphate ester (OPE) application have led to their widespread presence, yet little is known about their temporal trends in food. This study collected milk samples from 13 countries across three continents during 2020-2023, finding detectable OPEs in all samples (range: 2.25-19.7; median: 7.06 ng/g ww). Although no statistical temporal differences were found for the total OPEs during the 4-year sampling campaign, it was interesting to observe significant variations in the decreasing trend for Cl-OPEs and concentration variations for aryl-OPEs and alkyl-OPEs (p < 0.05), indicating changing OPE use patterns. Packaged milk exhibited significant higher OPE levels than those found in directly collected raw unpackaged milk, and milk with longer shelf-life showed higher OPE levels, revealing packaging material as a contamination source. No significant geographical differences were observed in milk across countries (p > 0.05), but Shandong Province, a major OPE production site in China, showed relatively higher OPE concentrations. The Monte Carlo simulation of estimated daily intakes indicated no exposure risk from OPEs through milk consumption. The molecular docking method was used to assess human hormone binding affinity with OPEs, amongst which aryl-OPEs had the highest binding energies. The Toxicological-Priority-Index method which integrated chemical property, detection frequency, risk quotients, hazardous quotients and endocrine-disrupting effects was employed to prioritize OPEs. Aryl-OPEs showed the highest scores, deserving attention in the future.

Photocatalytic activity and mechanism of YMnO3/NiO photocatalyst for the degradation of oil and gas field wastewater.

One-step hydrothermal method has been used to synthesize YMnO3@NiO (YMO@NO) photocatalysts with high photocatalytic activity for the degradation of oil and gas field wastewater under simulated solar irradiation. Through various characterization methods, it has been confirmed that the YMO@NO photocatalyst comprises only YMO and NO, without any other impurities. The microstructure characterization confirmed that the YMO@NO photocatalyst was composed of large squares and fine particles, and heterojunction was formed at the interface of YMO and NO. The optical properties confirm that the YMO@NO photocatalyst has high UV-vis optical absorption coefficient, suggesting that it has high UV-vis photocatalytic activity. Taking oil and gas field wastewater as degradation object, YMO@NO photocatalyst showed the highest photocatalytic activity (98%) when the catalyst content was 1.5 g/L, the mass percentage of NO was 3%, and the irradiation time was 60 min. Capture and stability experiments confirm that the YMO@NO photocatalyst is recyclable and electrons, holes, hydroxyl radicals and superoxide radicals play major roles in the photocatalysis process. Based on experiments and theoretical calculations, a reasonable photocatalytic mechanism of the YMO@NO photocatalyst is proposed.

Covalent organic framework aerogel for high-performance solid-phase extraction of tetracycline antibiotics: Experiment and simulated calculation on adsorption behavior.

Three-dimensional sponge-architecture covalent organic frameworks (COFs)-aerogel was successfully designed and synthesized via a freeze-drying template approach, and utilized as an efficient sorbent in solid-phase extraction (SPE). A method for selective enrichment of pharmaceutical contaminants including tetracycline, chlortetracycline, methacycline and oxytetracycline in the environment and food samples was proposed by combining with high performance liquid chromatography (HPLC). To understand the adsorption mechanism, selectivity test and molecular dynamics (MD) simulated calculation were both carried out. The experimental and in-silico results demonstrated that the COFs-aerogel possessed high selectivity for contaminants with H bond acceptors/donors and good efficiency with maximum adsorption capacity up to 294.1 mg/g. The SPE-based HPLC method worked well in the range of 8-1000 ng/mL, with the need of little dose of adsorbent and sample volume while no need of spectrometer, outgoing the reported adsorbents. Under the optimized conditions, the intra-day and inter-day relative standard deviations (RSD) of repeatability were within 2.78-6.29 % and 2.44-8.42 % (n = 5). The results meet the current detection requirement for practical applications, and could be extended for further design of promising adsorbents.

Sanguinarine Regulates Tumor-Associated Macrophages to Prevent Lung Cancer Angiogenesis Through the WNT/ß-Catenin Pathway.

Tumor-associated macrophage (TAM)-mediated angiogenesis in the tumor microenvironment is a prerequisite for lung cancer growth and metastasis. Therefore, targeting TAMs, which block angiogenesis, is expected to be a breakthrough in controlling the growth and metastasis of lung cancer. In this study, we found that Sanguinarine (Sang) inhibits tumor growth and tumor angiogenesis of subcutaneously transplanted tumors in Lewis lung cancer mice. Furthermore, Sanguinarine inhibited the proliferation, migration, and lumen formation of HUVECs and the expression of CD31 and VEGF by regulating the polarization of M2 macrophages in vitro. However, the inhibitory effect of Sanguinarine on angiogenesis remained in vivo despite the clearance of macrophages using small molecule drugs. Further high-throughput sequencing suggested that WNT/ß-Catenin signaling might represent the underlying mechanism of the beneficial effects of Sanguinarine. Finally, the ß-Catenin activator SKL2001 antagonized the effect of Sanguinarine, indicating that Sanguinarine can regulate M2-mediated angiogenesis through the WNT/ß-Catenin pathway. In conclusion, this study presents the first findings that Sanguinarine can function as a novel regulator of the WNT/ß-Catenin pathway to modulate the M2 macrophage polarization and inhibit angiogenesis, which has potential application value in immunotherapy and antiangiogenic therapy for lung cancer.

Solasonine Causes Redox Imbalance and Mitochondrial Oxidative Stress of Ferroptosis in Lung Adenocarcinoma.

Ferroptosis, a type of iron-dependent oxidative cell death caused by excessive lipid peroxidation, is emerging as a promising cancer therapeutic strategy. Solasonine has been reported as a potential compound in tumor suppression, which is closely linked to ferroptosis. However, ferroptosis caused by solasonine is insufficiently identified and elaborated in lung adenocarcinoma, a fatal disease with high morbidity and mortality rates. First, the biochemical and morphological changes in Calu-1 and A549 cells exposed to solasonine are observed using a cell death assay and a microscope. The cell viability assay is performed after determining the executive concentration of solasonine to assess the effects of solasonine on tumor growth in Calu-1 and A549 cells. The ferroptosis is then identified by using ferroptosis-related reagents on CCK-8, lipid peroxidation assessment, Fe2+, and ROS detection. Furthermore, the antioxidant system, which includes GSH, Cys, GPx4, SLC7A11, and mitochondrial function, is measured to identify the potential pathways. According to the results, solasonine precisely exerts antitumor ability in lung adenocarcinoma cells. Ferroptosis is involved in the solasonine-induced cell death, as well as the accumulation of lipid peroxide, Fe2+, and ROS. Moreover, the failures of antioxidant defense and mitochondrial damage are considered to make a significant contribution to the occurrence of ferroptosis caused by solasonine. The study describes the potential process of ferroptosis caused by solasonine when dealing with lung adenocarcinoma. This encouraging evidence suggests that solasonine may be useful in the treatment of lung cancer.

Radiogenomic Signatures of Oncotype DX Recurrence Score Enable Prediction of Survival in Estrogen Receptor-Positive Breast Cancer: A Multicohort Study.

Background Radiogenomics explores the association between imaging features and genomic assays to uncover relevant prognostic features; however, the prognostic implications of the derived signatures remain unclear. Purpose To identify preoperative radiogenomic signatures of estrogen receptor-positive breast cancer associated with the Oncotype DX recurrence score (RS) and to evaluate whether they are biomarkers for survival and responses to neoadjuvant chemotherapy (NACT). Materials and Methods In this retrospective multicohort study, three data sets were analyzed. The radiogenomic development data set, with preoperative dynamic contrast-enhanced MRI and RS data obtained between January 2016 and October 2019 was used to identify radiogenomic signatures. Prognostic implications of the imaging signatures were assessed by measuring overall survival and recurrence-free survival in the prognostic assessment data set using a multivariable Cox proportional hazards model. The therapeutic implication of the radiogenomic signatures was evaluated by determining their ability to predict the response to NACT using the treatment assessment data set obtained between August 2015 and March 2019. Prediction performance was estimated by using the area under the receiver operating characteristic curve (AUC). Results The final cohorts included a radiogenomic development data set with 130 women (mean age, 52 years ± 10 [standard deviation]), a prognostic assessment data set with 116 women (mean age, 48 years ± 9), and a treatment assessment data set with 135 women (mean age, 50 years ± 11). Radiogenomic signatures (n = 11) of texture and morphologic and statistical features were identified to generate the predicted RS (R2 = 0.33, P < .001). A predicted RS greater than 29.9 was associated with poor overall and recurrence-free survival (P = .001 and P = .007, respectively); predicted RS was greater in women with a good NACT response (30.51 ± 6.92 vs 27.35 ± 4.04 [responders vs nonresponders], P = .001). By combining the predicted RS and complementary features, the model achieved improved performance in prediction of the NACT response (AUC, 0.85; P < .001). Conclusion Radiogenomic signatures associated with genomic assays provide markers of prognosis and treatment in estrogen receptor-positive breast cancer. © RSNA, 2021 Online supplemental material is available for this article.

Haptically Quantifying Young's Modulus of Soft Materials Using a Self-Locked Stretchable Strain Sensor.

Simple and rapid Young's modulus measurements of soft materials adaptable to various scenarios are of general significance, and they require miniaturized measurement platforms with easy operation. Despite the advances made in portable and wearable approaches, acquiring and analyzing multiple or complicated signals necessitate tethered bulky components and careful preparation. Here, a new methodology based on a self-locked stretchable strain sensor to haptically quantify Young's modulus of soft materials (kPa-MPa) rapidly is reported. The method demonstrates a fingertip measurement platform, which endows a prosthetic finger with human-comparable haptic behaviors and skills on elasticity sensing without activity constraints. A universal strategy is offered toward ultraconvenient and high-efficient Young's modulus measurements with wide adaptability to various fields for unprecedented applications.

A Stretchable and Transparent Electrode Based on PEGylated Silk Fibroin for In Vivo Dual-Modal Neural-Vascular Activity Probing.

Transparent electrodes that form seamless contact and enable optical interrogation at the electrode-brain interface are potentially of high significance for neuroscience studies. Silk hydrogels can offer an ideal platform for transparent neural interfaces owing to their superior biocompatibility. However, conventional silk hydrogels are too weak and have difficulties integrating with highly conductive and stretchable electronics. Here, a transparent and stretchable hydrogel electrode based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and PEGylated silk protein is reported. PEGylated silk protein with poly(ethylene glycol) diglycidyl ether (PEGDE) improves the Young's modulus to 1.51-10.73 MPa and the stretchability to ≈400% from conventional silk hydrogels (<10 kPa). The PEGylated silk also helps form a robust interface with PEDOT:PSS thin film, making the hydrogel electrode synergistically incorporate superior stretchability (≈260%), stable electrical performance (≈4 months), and a low sheet resistance (≈160 ± 56 Ω sq-1 ). Finally, the electrode facilitates efficient electrical recording, and stimulation with unobstructed optical interrogation and rat-brain imaging are demonstrated. The highly transparent and stretchable hydrogel electrode offers a practical tool for neuroscience and paves the way for a harmonized tissue-electrode interface.

Highly Thermal-Wet Comfortable and Conformal Silk-Based Electrodes for On-Skin Sensors with Sweat Tolerance.

Noninvasive and seamless interfacing between the sensors and human skin is highly desired for wearable healthcare. Thin-film-based soft and stretchable sensors can to some extent form conformal contact with skin even under dynamic movements for high-fidelity signals acquisition. However, sweat accumulation underneath these sensors for long-term monitoring would compromise the thermal-wet comfort, electrode adherence to the skin, and signal fidelity. Here, we report the fabrication of a highly thermal-wet comfortable and conformal silk-based electrode, which can be used for on-skin electrophysiological measurement under sweaty conditions. It is realized through incorporating conducting polymers poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) into glycerol-plasticized silk fiber mats. Glycerol plays the role of tuning the mechanical properties of silk fiber mats and enhancing the conductivity of PEDOT:PSS. Our silk-based electrodes show high stretchability (>250%), low thermal insulation (∼0.13 °C·m2·W-1), low evaporative resistance (∼23 Pa·m2·W-1, 10 times lower than ∼1.3 mm thick commercial gel electrodes), and high water-vapor transmission rate (∼117 g·m-2·h-1 under sweaty conditions, 2 times higher than skin water loss). These features enable a better electrocardiography signal quality than that of commercial gel electrodes without disturbing the heat dissipation during sweat evaporation and provide possibilities for textile integration to monitor the muscle activities under large deformation. Our glycerol-plasticized silk-based electrodes possessing superior physiological comfortability may further engage progress in on-skin electronics with sweat tolerance.

Targeting Reactive Oxygen Species in Cancer via Chinese Herbal Medicine.

Recently, reactive oxygen species (ROS), a class of highly bioactive molecules, have been extensively studied in cancers. Cancer cells typically exhibit higher levels of basal ROS than normal cells, primarily due to their increased metabolism, oncogene activation, and mitochondrial dysfunction. This moderate increase in ROS levels facilitates cancer initiation, development, and progression; however, excessive ROS concentrations can lead to various types of cell death. Therefore, therapeutic strategies that either increase intracellular ROS to toxic levels or, conversely, decrease the levels of ROS may be effective in treating cancers via ROS regulation. Chinese herbal medicine (CHM) is a major type of natural medicine and has greatly contributed to human health. CHMs have been increasingly used for adjuvant clinical treatment of tumors. Although their mechanism of action is unclear, CHMs can execute a variety of anticancer effects by regulating intracellular ROS. In this review, we summarize the dual roles of ROS in cancers, present a comprehensive analysis of and update the role of CHM-especially its active compounds and ingredients-in the prevention and treatment of cancers via ROS regulation and emphasize precautions and strategies for the use of CHM in future research and clinical trials.

Proactively modulating mechanical behaviors of materials at multiscale for mechano-adaptable devices.

How materials behave when subjected to mechanical stresses is studied by mechanics of materials. However, the application of flexible and stretchable devices exposes materials to dynamic mechanical environments. Therefore, mechano-adaptable materials and devices that can respond as pre-designed have been explored. There are two main ways to proactively modulate mechanical behaviors for materials, which involve molecular design and structural design. Molecular design has effectively integrated mechanically sensitive groups into synthetic materials for anticipated mechano-response. Structural design has broadened the boundary of conventional materials, generating mechanical metamaterials at multiscale with unique mechanical properties. Furthermore, molecular, structural plus systematic design for the application of mechano-adaptable devices have realized better electrical performance, human interaction, long-term sustainability, and even higher efficiency. Various devices based on design ideas are summarized and future challenges for proactively modulating mechanical behaviors of mechano-adaptable devices are discussed.

Plasticizing Silk Protein for On-Skin Stretchable Electrodes.

Soft and stretchable electronic devices are important in wearable and implantable applications because of the high skin conformability. Due to the natural biocompatibility and biodegradability, silk protein is one of the ideal platforms for wearable electronic devices. However, the realization of skin-conformable electronic devices based on silk has been limited by the mechanical mismatch with skin, and the difficulty in integrating stretchable electronics. Here, silk protein is used as the substrate for soft and stretchable on-skin electronics. The original high Young's modulus (5-12 GPa) and low stretchability (<20%) are tuned into 0.1-2 MPa and > 400%, respectively. This plasticization is realized by the addition of CaCl2 and ambient hydration, whose mechanism is further investigated by molecular dynamics simulations. Moreover, highly stretchable (>100%) electrodes are obtained by the thin-film metallization and the formation of wrinkled structures after ambient hydration. Finally, the plasticized silk electrodes, with the high electrical performance and skin conformability, achieve on-skin electrophysiological recording comparable to that by commercial gel electrodes. The proposed skin-conformable electronics based on biomaterials will pave the way for the harmonized integration of electronics into human.

A small molecule probe reveals declined mitochondrial thioredoxin reductase activity in a Parkinson's disease model.

The first off-on probe, Mito-TRFS, for imaging the mitochondrial thioredoxin reductase (TrxR2) in live cells was reported. In a cellular model of Parkinson's disease (PD), Mito-TRFS staining discloses a drastic decline of the TrxR2 activity, providing a mechanistic link of TrxR2 dysfunction to the etiology of PD.

[Association of polymorphisms of p21cip1 and p27kip1 genes with susceptibilities of esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

BACKGROUND & OBJECTIVE: Researches showed that polymorphisms of p21(cip1) and p27(kip1) genes have associations with susceptibilities of breast cancer, lung cancer, prostate cancer, and so on. This study was to investigate the possible association of functional polymorphisms of p21(cip1) and p27(kip1) genes with susceptibilities of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population from a high incidence region in north China. METHODS: The single nucleotide polymorphisms (SNPs) in the 3'-untranslated region of p21(cip1) gene and in codon 109 of p27(kip1) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 299 ESCC patients, 256 GCA patients, and 437 healthy controls from a high incidence region of north China. RESULTS: The frequency of p21(cip1) T allelotype was significantly higher in ESCC patients than in healthy controls (42.8% vs. 36.7%, P=0.02). The frequency of p27(kip1) V allelotype was significantly higher in ESCC and GCA patients than in healthy controls (96.8% and 96.1% vs. 92.9%, P=0.001, P=0.02). The distribution of p21(cip1) genotypes among ESCC patients was significantly different from that among healthy controls (P=0.04); compared with the combination of the C/C and C/T genotypes, the T/T genotype significantly elevated the risk of developing ESCC [adjusted odds ratio (OR)=1.93, 95% confidence interval (CI)=1.12-3.94]. The distribution of p27(kip1) genotypes among ESCC and GCA patients were significantly different from that among healthy controls (P=0.002, P=0.01); compared with the combination of V/G and G/G genotypes, the V/V genotype significantly elevated the risk of developing ESCC and GCA (adjusted OR=2.44, 95% CI=1.21-4.02; adjusted OR=2.01, 95% CI=1.12-3.68). When stratified for smoking and family history of upper gastrointestinal cancers (UGIC), compared with the combination of V/G and G/G genetypes, the V/V genotype significantly elevated the risk of developing both ESCC and GCA in smokers (adjusted OR=2.24, 95% CI=1.14-4.03; adjusted OR=2.61, 95% CI=1.25-3.82) and ESCC in individuals with positive family history of UGIC (adjusted OR =2.04, 95% CI=1.04-3.43). The combination of p21(cip1) T/T and p27(kip1) V/V genotypes significantly elevated the risk of developing ESCC and GCA (adjusted OR=3.78, 95% CI=1.46-5.89; adjusted OR=2.56, 95% CI=1.06-4.78). CONCLUSION: In north China, p21(cip1) polymorphisms might be correlated with the susceptibility of ESCC, p27(kip1) polymorphisms might be correlated with the susceptibilities of ESCC and GCA, and they might have synergetic effect on ESCC and GCA development.

[Polymorphisms of thymidylate synthase gene and correlation of its protein expression to lymph node metastasis of esophageal squamous cell carcinoma].

BACKGROUND & OBJECTIVE: Thymidylate synthase (TS) is a key enzyme in DNA synthesis. The 28-bp tandem repeat in the 5'-untranslated region (UTR) of TS gene and the G/C single nucleotide polymorphism (SNP) of TS gene may modify the expression and activity of TS protein, therefore, may change the susceptibility and prognosis of tumors. This study was to explore the correlations of TS 5'-UTR polymorphism to lymph node metastasis of esophageal squamous cell carcinoma (ESCC) and the expression of TS protein. METHODS: Peripheral leucocyte DNA was extracted from 232 ESCC patients and 348 age-and gender-matched healthy controls. TS 5'-UTR tandem repeat and the G/C SNP genotype was detected by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. TS expression in 51 specimens of ESCC was detected by SP immunohistochemistry. RESULTS: The frequencies of 3G/3G, 3G/3C, 3C/3C, 2R/3G, 2R/3C, 2R/2R, and other genotypes were 17.5%, 17.3%, 29.3%, 12.9%, 17.8%, 3.7%, and 1.5% in the healthy controls, and 16.0%, 16.0%, 29.3%, 13.8%, 17.6%, 4.3%, and 3.0% in the ESCC patients; whereas the frequencies of 3G, 3C, 2R, and other alleles were 32.8%, 47.0%, 19.5%, and 0.7% in the healthy controls, and 31.2%, 46.8%, 20.5%, and 1.5% in the ESCC patients, respectively. Compared with 3G/3G genotype, 2R/3G genotype significantly increased the risk of lymph node metastasis of ESCC [age and gender adjusted odds ratio (OR), 11.53; 95% confidence interval (CI), 2.67-49.74]. TS protein expression was significantly related to TS 5'-UTR genotype (P<0.05), but was not related to gender, age, lymph node metastasis and clinicopathologic stage. CONCLUSION: TS 5'-UTR tandem repeat and G/C SNP genotype, but not TS expression, might be a candidate molecular marker to predict lymph node metastasis of ESCC.

[Association of thymidylate synthase polymorphism with esophageal squamous-cell carcinoma].

OBJECTIVE: To explore the influence of 5'UTR tandem repeat and 3'UTR 6 bp deletion polymorphism of thymidylate synthase (TS) gene on the development and lymphatic metastases of esophageal squamous-cell carcinoma (ESCC). METHODS: Peripheral leucocyte DNA was extracted from 232 ESCC patients and 348 age- and sex-matched healthy controls. TS 5'UTR and 3'UTR genotyping in all study subjects was performed by PCR fragment analysis and PCR-RFLP analysis, respectively. RESULTS: The distribution of TS 5'UTR and 3'UTR variants in ESCC patients was not significantly different from that in healthy controls. However, individuals with 6 bp+/6 bp+ and 3R/3R genotypes significantly reduced the risk to ESCC development compared to those with other genotype combinations (adjusted OR = 0.32, 95% CI = 0.08-0.92). In addition, the frequency of 2R/3R genotype in ESCC patients with lymphatic metastases (40%) was significantly higher than that in lymph node negative cases (14.7%) (chi(2) = 10.11, P = 0.001). Compared to 3R/3R genotype, the 2R/3R genotype significantly increased the risk of lymphatic metastases in ESCC (adjusted OR = 3.68, 95% CI = 1.54-8.93). CONCLUSION: The genotyping of TS 5'UTR and 3'UTR polymorphisms might be used as a stratification maker for predicting susceptibility to ESCC. The TS 5'UTR 2R/3R genotype might be a candidate molecular marker to predict the potential of lymphatic metastases in ESCC.

Association of the thymidylate synthase polymorphisms with esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma.

Polymorphisms in the untranslated regions (UTRs) of the thymidylate synthase (TS) gene, which may modulate TS transcription and expression, have been associated with susceptibility and prognosis of several tumors. However, their effects on the development and clinical staging of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) have not been assessed so far. In this study, the 28-bp tandem repeat and the G/C single nucleotide polymorphism in the TS 5'UTR, the 6-bp deletion (6 bp-) polymorphism in the TS 3'UTR, were genotyped in 465 cancer patients (232 ESCC, 233 GCA) and 348 control subjects in North China. The genotype and allelotype distribution of the TS variants in ESCC, GCA patients and controls did not show significant difference. However, the frequency of the 6 bp-/2R haplotype in ESCC and GCA patients was marginally or significantly lower than that in controls (P = 0.05 and 0.006, respectively). Thus, the 6 bp-/2R significantly reduced the risk to ESCC and GCA, compared with the 6 bp-/3G haplotype [odds ratio (OR) = 0.61 and 0.48, 95% confidence interval (CI) = 0.37-1.00 and 0.28-0.81, respectively]. In addition, the 6 bp+/3G haplotype in ESCC patients was also significantly less common than in controls (P = 0.002). Compared with the 6 bp-/3G haplotype, the 6 bp+/3G significantly reduced the risk to ESCC (OR = 0.30, 95% CI = 0.14-0.67). Moreover, the TS 2R/3G genotype frequency in ESCC patients with and without lymphatic metastasis was significantly different (27.1 versus 4.9%, P < 0.001). Therefore, the 2R/3G genotype had an approximately 11-fold increase in the risk of lymphatic metastasis of ESCC, compared with the 3G/3G genotype (95% CI = 2.67-49.74). The results suggested that the TS polymorphisms might be associated with the susceptibility to ESCC and GCA, and the 2R/3G genotype might be a candidate marker to predict the potential of lymphatic metastasis in ESCC.