Co-occurring EGFR p.E709X mutation Mediates Primary Resistance to the Third-generation EGFR-TKIs in EGFR p.G719X-mutant Patients with Advanced NSCLC.

PURPOSE: Current NCCN guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4228 treatment-naïve patients with lung cancer who underwent targeted NGS testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib(n=37) and the third-generation EGFR-TKIs(n=31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. RESULTS: Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC(~30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI(G719X/E709X vs. G719X; ORR:0.00% vs. 47.62%, P<0.001; mPFS:7.18 vs. 14.2 months, P=0.04; respectively). Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients(G719X/E709X vs. G719X; ORR:71.43% vs. 56.67%, P=0.99; mPFS:14.7 vs. 15.8 months, P=0.69; respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKIs treatment. CONCLUSION: Co-occurring EGFR p.E709X mutation mediates primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the co-existing EGFR p.E709X mutation status.

Live Cell Imaging and Real-Time Monitoring of Nucleolus Morphology and Mitophagy with a Red Fluorescent and Photostable rRNA-Specific Probe in Human Cancer Cells.

rRNAs are prevalent in living organisms. They are produced in nucleolus and mitochondria and play essential cellular functions. In addition to the primary biofunction in protein synthesis, rRNAs have been recognized as the emerging signaling molecule and drug target for studies on nucleolus morphology, mitochondrial autophagy, and tumor cell malignancy. Currently, only a few rRNA-selective probes have been developed, and most of them encounter the drawbacks of low water solubility, poor nuclear membrane permeability, short emission wavelength, low stability against photobleaching, and high cytotoxicity. These unfavorable properties of rRNA probes limit their potential applications. In the present study, we reported a new rRNA-selective and near-infrared fluorescent turn-on probe, 4MPS-TO, capable of tracking rRNA in live human cancer cells. The real-time monitoring performance in nucleolus morphology and mitochondrial autophagy is demonstrated in HeLa cells. The probe shows great application potential for being used as a rRNA-selective, sensitive, and photostable imaging tool in chemical biology study and drug screening.

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study.

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.

Genomic characteristics and drug screening among organoids derived from non-small cell lung cancer patients.

BACKGROUND: Patient-derived organoid (PDO) models are highly valuable and have potentially widespread clinical applications. However, limited information is available regarding organoid models of non-small cell lung cancer (NSCLC). This study aimed to characterize the consistency between primary tumors in NSCLC and PDOs and to explore the applications of PDOs as preclinical models to understand and predict treatment response during lung cancer. METHODS: Fresh tumor samples were harvested for organoid culture. Primary tumor samples and PDOs were analyzed via whole-exome sequencing. Paired samples were subjected to immunohistochemical analysis. There were 26 antineoplastic drugs tested in the PDOs. Cell viability was assessed using the Cell Titer Glo assay 7-10 days after drug treatment. A heatmap of log-transformed values of the half-maximal inhibitory concentrations was generated on the basis of drug responses of PDOs through nonlinear regression (curve fit). A total of 12 patients (stages I-III) were enrolled, and 7 paired surgical tumors and PDOs were analyzed. RESULTS: PDOs retained the histological and genetic characteristics of the primary tumors. The concordance between tumors and PDOs in mutations in the top 20 NSCLC-related genes was >80% in five patients. Sample purity was significantly and positively associated with variant allele frequency (Pearson r = 0.82, P = 0.0005) and chromosome stability. The in vitro response to drug screening with PDOs revealed high correlation with the mutation profiles in the primary tumors. CONCLUSIONS: PDOs are highly credible models for detecting NSCLC and for prospective prediction of the treatment response for personalized precision medicine. KEY POINTS: Lung cancer organoid models could save precious time of drug testing on patients, and accurately select anticancer drugs according to the drug sensitivity results, so as to provide a powerful supplement and verification for the gene sequencing.

Inhibition of Rac1 activity by NSC23766 prevents cartilage endplate degeneration via Wnt/ß-catenin pathway.

Cartilage endplate (CEP) degeneration has been considered as one of important factors related to intervertebral disc degeneration (IVDD). Previous researches have showed that Rac1 played a pivotal role in chondrocyte differentiation. However, the effect of Rac1 during the process of CEP degeneration remains unclear. Herein, we explored the effect of Rac1 on CEP degeneration and elucidated the underlying molecular mechanism. We found expression of Rac1-GTP increased in human-degenerated CEP tissue and IL-1ß-stimulated rat endplate chondrocytes (EPCs). Our study revealed that Rac1 inhibitor NSC23766 treatment promoted the expression of collagen II, aggrecan and Sox-9, and decreased the expression of ADTAMTS5 and MMP13 in IL-1ß-stimulated rat EPCs. Moreover, we also found that NSC23766 could suppress the activation of Wnt/ß-catenin pathway, suggesting that the beneficial effects of Rac1 inhibition in EPCs are mediated through the Wnt/ß-catenin signalling. Besides, puncture-induced rats models showed that NSC23766 played a protective role on CEP and disc degeneration. Collectively, these findings demonstrated that Rac1 inhibition delayed the EPCs degeneration and its potential mechanism may be associated with Wnt/ß-catenin pathway regulation, which may help us better understand the association between Rac1 and CEP degeneration and provide a promising strategy for delaying the progression of IVDD.

Projection of the Most Anterior Line of the Spinal Canal on Lateral Radiograph: An Anatomic Study for Percutaneous Kyphoplasty and Percutaneous Vertebroplasty.

ABSTRACTPurpose: To measure the projection of the most anterior line of the spinal canal on lateral radiographs of the vertebra (C3-L5) and evaluate the efficacy of the safety line (SL) in preventing intraspinal cement leakage in percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Materials and Methods: Fifteen adult dry-bone spine specimens were analyzed. The projection of the SL was viewed on lateral radiographs. The distance between the SL and the posterior vertebral body line (PVBL) was measured. Two groups of patients were treated by PKP, and cement injection was stopped either before the PBVL (group 1) or before the SL (group 2) under lateral fluoroscopy. The rate of cement leakage was compared between the two groups. Results: The largest distance between the SL and PVBL was at L1 (5.22 ± 0.62 mm). From L1 to L5, the distance decreased progressively to 1.05 ± 0.64 mm. Similar variation was also observed from L1 to T1 (0.19 ± 0.18 mm). The postoperative computed tomography scan was more sensitive and accurate in detecting intraspinal leakage than radiography in group 1 (p = 0.000); however, there was no significant difference in sensitivity or accuracy between methods in group 2 (p = 0.063). The rate of intraspinal cement leakage was significantly higher in group 1 than group 2 (p = 0.000). Conclusions: The operator should frequently check to ensure that cement injection has stopped upon reaching the SL. Surgeons may benefit from this quantitative anatomical study of PKP and PVP.

The projection of the thoracic nerve roots and their connection with intervertebral discs: a cadaver and radiological study.

BACKGROUND: The anatomical features of the thoracic nerve roots in connection with intervertebral discs may prevent surgery-related complications and improve patients' neurological functional status during thoracic spine surgery. There is limited literature evidence regarding this concept using cadavers. PURPOSE: To elucidate the qualitative anatomical features of the thoracic nerve roots in connection with intervertebral discs. MATERIAL AND METHODS: Fifteen formalin-preserved spine specimens were used in this study. Small pieces of stainless-steel wires were placed along the root sleeves from their points of origin, after exposing the dural sac and bilateral nerve roots. The standard anteroposterior and lateral radiographs were taken after the placement of the wires. Measurements were done on radiographs using the picture archiving communication system. RESULTS: Take-off angles of the nerve roots at the coronal plane gradually increased from the level of T2 (36.1°±2.72°) to T9 (84.1°±1.84°) and from T9, it decreased to T12 (46.3° ± 2.67°). Similar variation tendency was discovered in take-off angles of the nerve roots at the sagittal plane. No consistent tendency was found both in the distance from the origin of the root sleeve to its superior and inferior vertebral endplate. Distance from the origin of the root sleeve to the posterior midline (DM) exponentially decreased from T1 (8.2 ± 0.87 mm) to T4 (6.0 ± 0.93 mm). It slowly increased from T5 (5.5 ± 0.68 mm) to T12 (10.9 ± 1.79 mm), with T5 having the smallest DM. Distance between the origins of neighboring nerve roots showed an obvious increase from the T1-T2 interval (23.1 ± 2.22 mm) to T7-T8 interval (30.9 ± 2.68 mm). However, it progressively decreased at the T10-T11 interval (26.0 ± 2.40 mm). CONCLUSION: The dimensions of the thoracic nerve roots vary greatly from T1 to T12 intervertebral discs. Sound knowledge of these anatomical features of the thoracic nerve is mandatory for the thoracic spine surgery, especially in the posterolateral approach and transforaminal endoscopic surgery.

Cyanidin ameliorates the progression of osteoarthritis via the Sirt6/NF-κB axis in vitro and in vivo.

Osteoarthritis (OA) is the most prevalent form of human arthritis which is characterized by the degradation of cartilage and inflammation. As a rare Sirt6 activator, cyanidin is the major component of anthocyanins commonly found in the Mediterranean diet, and increasing evidence has shown that cyanidin exhibits anti-inflammatory effects in a variety of diseases. However, the anti-inflammatory effects of cyanidin on OA have not been reported. In the present study, we identified that cyanidin treatment could strongly suppress the expression of NO, PGE2, TNF-α, IL-6, iNOs, COX-2, ADAMTS5 and MMP13, and reduce the degradation of aggrecan and collagen II in IL-1ß-induced human OA chondrocytes, indicating the anti-inflammatory effect of cyanidin. Further investigation of the mechanism involved revealed that cyanidin could upregulate the Sirt6 level in a dose-dependent manner and Sirt6 silencing abolished the effect of cyanidin in IL-1ß-stimulated human OA chondrocytes, indicating a stimulatory effect of cyanidin on Sirt6 activation. Meanwhile, we found that cyanidin could inhibit the NF-κB pathway in IL-1ß-stimulated human OA chondrocytes and its effect may to some extent depend on Sirt6 activation, suggesting that cyanidin may exert a protective effect through regulating the Sirt6/NF-κB signaling axis. Moreover, the in vivo study also proved that cyanidin ameliorated the development of OA in surgical destabilization of the medial meniscus (DMM) mouse OA models. In conclusion, these results demonstrate that cyanidin may have therapeutic potential for the treatment of OA.

Vacuum Facet Phenomenon in Computed Tomography Imaging: A Sign of Instability in Degenerative Spondylolisthesis?

OBJECTIVE: The aim of the present study was to investigate the relationship between vacuum facet phenomena and lumbar instability in patients with degenerative spondylolisthesis (DS) in L4-L5. METHODS: Patients with L4-L5 DS who had both lumbosacral flexion-extension radiographs and computed tomography (CT) scans available for review from January 2016 to December 2017 were eligible for the present study. The dynamic motion index (DMI) of each patient was used to represent the percentage of slippage of L-L4 on the L5 vertebral disks on the flexion radiographs minus the percentage on the extension radiographs. The facet vacuum index refers to the average width of the facet vacuum on the left and right sides. RESULTS: A total of 67 patients with L4-L5 DS were included in the present study. Of the 67 patients, 35 had a vacuum facet phenomenon on their CT scan and 32 patients did not. The incidence of lumbar instability in the patients with a vacuum facet phenomenon was significantly greater than that in the patients without a vacuum facet phenomenon (P = 0.015). The mean DMI for the patients with a vacuum facet phenomenon was significantly greater than that for the patients without a vacuum facet phenomenon (P < 0.001). A positive linear correlation was found between the facet vacuum index and DMI for patients with a vacuum facet phenomenon (Pearson correlation coefficient, 0.597; P < 0.001). CONCLUSIONS: A linear correlation was found between the degree of segmental motion and the width of the vacuum facet phenomenon in patients with DS at L4-L5. Our study has shown that vacuum facet phenomena detected on the CT images of patients with DS are highly predictive of segmental instability.

Comparison of Hidden Blood Loss Between Three Different Surgical Approaches for Treatment of Thoracolumbar Fracture.

Purpose: To examine the hidden blood loss (HBL) in treatment of AO type A1-A3 thoracolumbar fractures with three different approaches and to explore the influential factors of HBL among patients after the surgery of internal fixation for thoracolumbar fractures. Methods: We retrospectively studied 85 patients in treatment of thoracolumbar fractures: 25 patients via percutaneous approach (Group A), 33 patients via paraspinal approach (Group B), and 27 patients via conventional open approach (Group C). The demographic information of the patients was collected. Each patient's preoperative and postoperative hematocrit were recorded and used for calculating the blood loss according to the Gross's formula. The difference of blood loss between the three groups was measured by ANOVA. And influential factors were further analyzed by multivariate linear regression analysis in each group. Results: The average HBL was 240.0 ± 65.1 mL in Group A, 313.7 ± 138.1 mL in Group B, and 382 ± 153.8 mL in Group C. There was statistical difference in the HBL between three groups (P = 0.000). However, multivariate linear regression analysis revealed that HBL of three approaches was not associated with age, gender, body mass index (BMI), percentage of height loss, percentage of height restoration, fracture type, or operation time. Conclusion: There was a substantial HBL in the treatment of thoracolumbar fractures, which was neglected by surgeons. Further investigation is necessary to study the risk factors for surgery on HBL in treatment of thoracolumbar fractures.

Comparison of plate and intramedullary nail fixation of extra-articular tibial fractures: A retrospective study exploring hidden blood loss.

PURPOSE: To explore the hidden blood loss (HBL) in treatment of extra-articular tibial fractures with plate and intramedullary nail fixation. METHODS: We conducted a retrospective study including 209 consecutive patients treated by plate (Group LCP) or intramedullary nail fixation (Group IMN) for extra-articular tibial fractures between January 2015 to December 2017. Demographics, intraoperative data, perioperative laboratory values, transfusion rate, and early complications were collected and analyzed. RESULTS: Of 209 patients, 96 patients fixed with IMN and 113 fixed with LCP. The average HBL was 272.71 ± 57.88 ml in Group LCP and 507.66 ± 109.81 ml in Group IMN, and there was statistical difference in the HBL between two groups (p < 0.001). The Hb and Hct loss, surgical duration, and postoperative number of anemic patients in Group IMN were significantly higher than in Group LCP (p < 0.001), and IMN fixation has a significantly higher rate of transfusion (p = 0.027), whereas patients in group IMN has significantly less VBL (p < 0.001), shorter postoperative hospital stay (p < 0.001), and less superficial infection (p = 0.014). CONCLUSIONS: There was a significant amount of hidden blood loss after reamed intramedullary nail fixation for extra-articular tibial fractures, which was much higher than expected. In view of the morbidity of acute anaemia and transfusion, we suggest that for patients who suffer from extra-articular tibial fractures with multiple injuries, or those with low haemoglobin preoperatively, plates might be more suitable than nail fixation.

Sophocarpine attenuates wear particle-induced implant loosening by inhibiting osteoclastogenesis and bone resorption via suppression of the NF-κB signalling pathway in a rat model.

BACKGROUND AND PURPOSE: Aseptic prosthesis loosening, caused by wear particles, is one of the most common causes of arthroplasty failure. Extensive and over-activated osteoclast formation and physiological functioning are regarded as the mechanism of prosthesis loosening. Therapeutic modalities based on inhibiting osteoclast formation and bone resorption have been confirmed to be an effective way of preventing aseptic prosthesis loosening. In this study, we have investigated the effects of sophocarpine (SPC, derived from Sophora flavescens) on preventing implant loosening and further explored the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of SPC in inhibiting osteoclastogenesis and bone resorption were evaluated in osteoclast formation, induced in vitro by the receptor activator of NF-κB ligand (RANKL). A rat femoral particle-induced peri-implant osteolysis model was established. Subsequently, micro-CT, histology, mechanical testing and bone turnover were used to assess the effects of SPC in preventing implant loosening. KEY RESULTS: In vitro, we found that SPC suppressed osteoclast formation, bone resorption, F-actin ring formation and osteoclast-associated gene expression by inhibiting NF-κB signalling, specifically by targeting IκB kinases. Our in vivo study showed that SPC prevented particle-induced prosthesis loosening by inhibiting osteoclast formation, resulting in reduced periprosthetic bone loss, diminished pseudomembrane formation, improved bone-implant contact, reduced bone resorption-related turnover and enhanced stability of implants. Inhibition of NF-κB signalling by SPC was confirmed in vivo. CONCLUSION AND IMPLICATIONS: SPC can prevent implant loosening through inhibiting osteoclast formation and bone resorption. Thus, SPC might be a novel therapeutic agent to prevent prosthesis loosening and for osteolytic diseases.

Anterior endoscopically assisted bone grafting for iatrogenic distraction of odontoid fracture after percutaneous anterior screw fixation: A case report.

RATIONALE: The complication of iatrogenic distraction of odontoid fracture after anterior screw fixation has not been reported in the literature. We treated the patient with endoscopically assisted bone grafting with good results. The new technique was not reported in the management of odontoid fracture or nonunion before. PATIENT CONCERNS: A 22-year-old man presented with neck pain after a motorcycle crash. The cervical spine radiograph and computed tomographic scan demonstrated the base of dens displaced 2 mm anteriorly. DIAGNOSES: Radiographic images showed a type II odontoid fracture. INTERVENTIONS: The patient was treated by percutaneous anterior screw fixation. The postoperative radiograph and CT demonstrated an iatrogenic distraction of the odontoid with a gap of 6 mm.The follow-up radiograph did not show any sign of bone union 1 month and a half later. A revision surgery was given by anterior endoscopically assisted bone grafting. The patient was encouraged to sit out of bed immediately after the surgery with the protection of a soft cervical collar for 3 months. OUTCOMES: No complications such as neural structures or vascular injuries were found. Bone union was achieved at the 1-year follow-up CT scans. Physical examination showed a full range of motion in the neck. LESSONS: We reported a case of iatrogenic odontoid distraction that was managed by anterior endoscopically assisted bone grafting. It is a technically feasible and minimally invasive procedure.

Comparison of the Total and Hidden Blood Loss in Patients Undergoing Open and Minimally Invasive Transforaminal Lumbar Interbody Fusion.

PURPOSE: This study examined the volume of hidden blood loss (HBL) and compared perioperative blood loss between minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and open transforaminal lumbar interbody fusion (O-TLIF). METHODS: Forty-eight patients who were treated with MI-TLIF and 59 patients treated with O-TLIF were enrolled in this study. Patients' height, weight, and preoperative and postoperative hematocrit (Hct) were recorded and used to calculate total blood loss (TBL) according to the Gross formula. Each patient's HBL was calculated. The data were further analyzed by the Student t test and the χ2 test. RESULTS: The visible blood loss (VBL) was 186 ± 95 mL in the MI-TLIF; however, the HBL (423 ± 233 mL; 66.5 ± 16.1% of TBL) was twice the VBL. The VBL in the O-TLIF group was 471 ± 147 mL, and the HBL was 271 ± 223 mL (31.3 ± 23.9% of TBL). Although TBL in MI-TLIF (602 ± 251 mL) was less than in O-TLIF (742 ± 275 mL), the HBL was significantly higher (P < 0.01). No difference in postoperative blood loss was observed between the 2 groups. Seven and 10 patients had preoperative anemia in the MI-TLIF group and the O-TLIF group, respectively, and 32 and 45 postoperatively. CONCLUSION: HBL is seriously underestimated and accounts for a large percentage of TBL in both MI-TLIF and O-TLIF. A correct understanding of HBL can ensure patient safety and improve postoperative rehabilitation.

Hidden blood loss and the influential factors after percutaneous kyphoplasty surgery.

PURPOSE: Percutaneous kyphoplasty (PKP) is a minimally invasive procedure for the treatment of osteoporotic vertebral compression fractures (OVCFs). It is generally considered that there is little blood loss during the surgery. However, a significant perioperative hidden blood loss (HBL) is neglected. This study was to examine the amount of HBL and determine the influential factors during PKP. METHODS: From January 2015 to January 2016, 115 patients with OVCFs who were scheduled to have a PKP were enrolled in this study. The factors analyzed included gender, age, body mass index (BMI), percentage of vertebral height loss, percentage of vertebral height restoration, number of fracture levels, bone mineral density (BMD), duration of symptom, cement leakage, and other internal diseases (hypertension, diabetes mellitus). According to Gross's formula, each patient's height, weight, and pre-operative and post-operative hematocrit were recorded and used for calculating the blood loss. Influential factors were further analyzed by multivariate linear regression analysis and t test. RESULTS: The mean HBL was 282 ± 162 mL (mL) and the post-operative Hb loss was 8.7 ± 5.4 g per liter (g/L). According to multivariate linear regression analysis, patients with severe vertebral height loss (P = 0.016), better vertebral height restoration (P = 0.038), and multi-segmental vertebral fractures (P = 0.000) had a higher amount of HBL. Fresh fractures (P = 0.008) and cement leakage (P = 0.004) were also important factors to increase HBL, whereas gender (P = 0.642), age (P = 0.203), BMI (P = 0.075), hypertension (P = 0.099), diabetes mellitus (P = 0.905), and BMD (P = 0.521) were not correlate with HBL. When we compared the incidence of anemia between pre-operative and post-operative, we found that the incidence of anemia was significantly associated with HBL (P = 0.000). CONCLUSIONS: HBL cannot be ignored in perioperative period, especially for poor physical condition and multiple fractures patients. Having a correct understanding of HBL can help improve clinical assessment capabilities, ensuring patients' safety.

RPSA gene mutants associated with risk of colorectal cancer among the chinese population.

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and 387 patients with CRC was conducted in a Chinese population. Information about socio-demography and living behavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibility to CRC and influence the protective effect of tea consumption in the Chinese population.