Value of Quantitative CTTA in Differentiating Malignant From Benign Bosniak III Renal Lesions on CT Images.

OBJECTIVE: The aim of this study was to investigate whether computed tomography texture analysis can differentiate malignant from benign Bosniak III renal lesions on computed tomography (CT) images. METHODS: This retrospective case-control study included 45 patients/lesions (22 benign and 23 malignant lesions) with Bosniak III renal lesions who underwent CT examination. Axial image slices in the unenhanced phase, corticomedullary phase, and nephrographic phase were selected and delineated manually. Computed tomography texture analysis was performed on each lesion during these 3 phases. Histogram-based, gray-level co-occurrence matrix, and gray-level run-length matrix features were extracted using open-source software and analyzed. In addition, receiver operating characteristic curve was constructed, and the area under the receiver operating characteristic curve (AUC) of each feature was constructed. RESULTS: Of the 33 extracted features, 16 features showed significant differences (P < 0.05). Eight features were significantly different between the 2 groups after Holm-Bonferroni correction, including 3 histogram-based, 4 gray-level co-occurrence matrix, and 1 gray-level run-length matrix features (P < 0.01). The texture features resulted in the highest AUC of 0.769 ± 0.074. Renal cell carcinomas were labeled with a higher degree of lesion gray-level disorder and lower lesion homogeneity, and a model incorporating the 3 most discriminative features resulted in an AUC of 0.846 ± 0.058. CONCLUSIONS: The results of this study showed that CT texture features were related to malignancy in Bosniak III renal lesions. Computed tomography texture analysis might help in differentiating malignant from benign Bosniak III renal lesions on CT images.

An Artificial Phase-Transitional Underwater Bioglue with Robust and Switchable Adhesion Performance.

Complex coacervation enables important wet adhesion processes in natural and artificial systems. However, existed synthetic coacervate adhesives show limited wet adhesion properties, non-thermoresponsiveness, and inferior biodegradability, greatly hampering their translations. Herein, by harnessing supramolecular assembly and rational protein design, we present a temperature-sensitive wet bioadhesive fabricated through recombinant protein and surfactant. Mechanical performance of the bioglue system is actively tunable with thermal triggers. In cold condition, adhesion strength of the bioadhesive was only about 50 kPa. By increasing temperature, the strength presented up to 600 kPa, which is remarkably stronger than other biological counterparts. This is probably due to the thermally triggered phase transition of the engineered protein and the formation of coacervate, thus leading to the enhanced wet adhesion bonding.

MicroRNA-374a Inhibits Aggressive Tumor Biological Behavior in Bladder Carcinoma by Suppressing Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. METHODS: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. RESULTS: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of ß-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. CONCLUSION: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma.

PURPOSE: Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated. METHODS: MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer. RESULTS: Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9. CONCLUSIONS: These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.

MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma.

Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC.

Hydrogel: a new material for intravesical drug delivery after bladder cancer surgery.

The standard treatment for non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT). However, this procedure may miss small lesions or incompletely remove them, resulting in cancer recurrence or progression. As a result, intravesical instillation of chemotherapy or immunotherapy drugs is often used as an adjunctive treatment after TURBT to prevent cancer recurrence. In the traditional method, drugs are instilled into the patient's bladder through a urinary catheter under sterile conditions. However, this treatment exposes the bladder mucosa to the drug directly, leading to potential side effects like chemical cystitis. Furthermore, this treatment has several limitations, including a short drug retention period, susceptibility to urine dilution, low drug permeability, lack of targeted effect, and limited long-term clinical efficacy. Hydrogel, a polymer material with a high-water content, possesses solid elasticity and liquid fluidity, making it compatible with tissues and environmentally friendly. It exhibits great potential in various applications. One emerging use of hydrogels is in intravesical instillation. By employing hydrogels, drug dilution is minimized, and drug absorption, retention, and persistence in the bladder are enhanced due to the mucus-adhesive and flotation properties of hydrogel materials. Furthermore, hydrogels can improve drug permeability and offer targeting capabilities. This article critically examines the current applications and future prospects of hydrogels in the treatment of bladder cancer.

Molecularly Engineered Protein Glues with Superior Adhesion Performance.

Naturally inspired proteins are investigated for the development of bioglues that combine adhesion performance and biocompatibility for biomedical applications. However, engineering such adhesives by rational design of the proteins at the molecular level is rarely reported. Herein, it is shown that a new generation of protein-based glues is generated by supramolecular assembly through de novo designed structural proteins in which arginine triggers robust liquid-liquid phase separation. The encoded arginine moieties significantly strengthen multiple molecular interactions in the complex, leading to ultrastrong adhesion on various surfaces, outperforming many chemically reacted and biomimetic glues. Such adhesive materials enable quick visceral hemostasis in 10 s and outstanding tissue regeneration due to their robust adhesion, good biocompatibility, and superior antibacterial capacity. Remarkably, their minimum inhibitory concentrations are orders of magnitude lower than clinical antibiotics. These advances offer insights into molecular engineering of de novo designed protein glues and outline a general strategy to fabricate mechanically strong protein-based materials for surgical applications.

Long-Lasting Proteinaceous Nanoformulation for Tumor Imaging and Therapy.

Nanodrugs have attracted increasing interest in drug delivery and disease treatment. However, the cumbersome preparation process and the poor biocompatibility of nanodrugs obstruct their clinical translation. In this study, we utilized a self-assembly strategy to develop a low-toxicity, long-lasting nanodrug for the effective treatment and real-time monitoring of bladder tumors. The accurate self-assembly of compatible raw materials allowed for an encapsulation rate of 43.7% for insoluble erdafitinib. Interestingly, robust therapeutic effects and reduced side effects could be realized simultaneously using this nanodrug, enabling broader scenarios for the clinical application of erdafitinib. Furthermore, the nanodrug exhibited a significantly prolonged in vivo half-life (14.4 h) and increased bioavailability (8.0 µg/mL·h), which were 8.3 times and 5.0 times higher than those of its nonformulated counterpart. Also, it is worth mentioning that the introduction of a fluorescent protein module into the nanodrug brought up a novel possibility for real-time feedback on the therapeutic response. In conclusion, this research revealed a versatile technique for developing low-toxicity, long-acting, and multifunctional nanoformulations, paving the way for multidimensional therapy of malignant tumors.

Correlations between hippocampal functional connectivity, structural changes, and clinical data in patients with relapsing-remitting multiple sclerosis: a case-control study using multimodal magnetic resonance imaging.

Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention, memory, and the speed of information processing. The hippocampus, which is a brain important structure involved in memory, undergoes microstructural changes in the early stage of multiple sclerosis. In this study, we analyzed hippocampal function and structure in patients with relapsing-remitting multiple sclerosis and explored correlations between the functional connectivity of the hippocampus to the whole brain, changes in local brain function and microstructure, and cognitive function at rest. We retrospectively analyzed data from 20 relapsing-remitting multiple sclerosis patients admitted to the Department of Neurology at the China-Japan Union Hospital of Jilin University, China, from April 2015 to November 2019. Sixteen healthy volunteers were recruited as the healthy control group. All participants were evaluated using a scale of extended disability status and the Montreal cognitive assessment within 1 week before and after head diffusion tensor imaging and functional magnetic resonance imaging. Compared with the healthy control group, the patients with relapsing-remitting multiple sclerosis had lower Montreal cognitive assessment scores and regions of simultaneously enhanced and attenuated whole-brain functional connectivity and local functional connectivity in the bilateral hippocampus. Hippocampal diffusion tensor imaging data showed that, compared with the healthy control group, patients with relapsing-remitting multiple sclerosis had lower hippocampal fractional anisotropy values and higher mean diffusivity values, suggesting abnormal hippocampal structure. The left hippocampus whole-brain functional connectivity was negatively correlated with the Montreal cognitive assessment score (r = -0.698, P = 0.025), and whole-brain functional connectivity of the right hippocampus was negatively correlated with extended disability status scale score (r = -0.649, P = 0.042). The mean diffusivity value of the left hippocampus was negatively correlated with the Montreal cognitive assessment score (r = -0.729, P = 0.017) and positively correlated with the extended disability status scale score (r = 0.653, P = 0.041). The right hippocampal mean diffusivity value was positively correlated with the extended disability status scale score (r = 0.684, P = 0.029). These data suggest that the functional connectivity and presence of structural abnormalities in the hippocampus in patients with relapse-remission multiple sclerosis are correlated with the degree of cognitive function and extent of disability. This study was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University, China (approval No. 201702202) on February 22, 2017.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Hypoxia Alleviating PdTe Nanoenzymes for Thermoradiotherapy.

Hypoxia in the tumor microenvironment induces radioresistance in cancer cells, which reduces the treatment efficiency of radiotherapy. Therefore, it is critical to produce sufficient oxygen to alleviate hypoxia to enhance the effect of ionizing radiation. Here, we constructed nanorod-shaped PdTe nanoenzymes to overcome hypoxia and promote the effects of thermoradiotherapy. Both palladium and tellurium are high-Z elements, which interacted with X-rays to generate more DNA radicals in the tumor regions. Moreover, PdTe nanoenzyme could catalyze the conversion of intratumoral overexpressed H2O2 to oxygen, alleviating hypoxia in the tumor regions. Photothermal therapy mediated by PdTe nanoenzymes not only ablated tumors but also accelerated the blood flow, in turn, modulating hypoxia. With good biocompatibility, PdTe nanoenzyme exhibited remarkable oxygen generation ability both in vitro and in vivo, indicating potential ability for radiosensitization. Further investigation using MBT-2 cells and MBT-2 tumor-bearing mice demonstrated that PdTe nanoenzyme could effectively enhance the treatment efficiency of radiotherapy. Thus, our work presented a novel nanoenzyme to overcome hypoxia in tumors for effective thermoradiotherapy.

Altered expression of striatin-4 is associated with poor prognosis in bladder transitional cell carcinoma.

Striatin-4 (STRN4 or Zinedin) is a scaffolding protein belonging to the mammalian STRN family of proteins and consists of multiple functional signaling domains. Due to its numerous signaling complexes, STRN4 has been reported to be involved in the tumorigenesis of various cancer types, including colon cancer, liver cancer and prostate cancer. However, few studies on STRN4 have been conducted in bladder cancer, and its prognostic role in bladder cancer remains unknown. The present study aimed to investigate the expression levels of STRN4 in bladder transitional cell carcinoma and evaluate the prognostic role of STRN4. STRN4 expression in clinical specimens was analyzed using immunohistochemistry and reverse transcription-quantitative PCR. It was demonstrated that STRN4 expression was significantly associated with clinical parameters such as tumor size, muscle invasion depth and pathological tumor grade. Abnormal STRN4 expression was typically associated with worse overall survival time and outcome when compared with the low STRN4 expression group. Using multivariate analysis, it was reported that STRN4 was an independent prognostic biomarker for survival time in bladder transitional cell carcinoma. Although the specific biological mechanisms of STRN4 in bladder cancer still remain to be elucidated, STRN4 expression could be a prognostic indicator in bladder cancer.

Review of Value of CT Texture Analysis and Machine Learning in Differentiating Fat-Poor Renal Angiomyolipoma from Renal Cell Carcinoma.

The diagnosis of patients with suspected angiomyolipoma relies on the detection of abundant macroscopic intralesional fat, which is always of no use to differentiate fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma and diagnosis of fp-AML excessively depends on individual experience. Texture analysis was proven to be a potentially useful biomarker for distinguishing between benign and malignant tumors because of its capability of providing objective and quantitative assessment of lesions by analyzing features that are not visible to the human eye. This review aimed to summarize the literature on the use of texture analysis to diagnose patients with fat-poor angiomyolipoma vs those with renal cell carcinoma and to evaluate its current application, limitations, and future challenges in order to avoid unnecessary surgical resection.

Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect.

Over 30 years' successful application of Bacillus Calmette Guerin (BCG) to the clinical treatment of bladder cancer has proved it one of the most promising immunotherapies for cancer. However, the applications and achievements have failed to uncover the mechanism of BCG works on bladder cancer fully. Clinically, the administration of BCG on patients results in no effect, or apparent resistance, and even severe adverse reactions, which are inexplicable. At present, the widely confirmed and accepted immunity mechanism of BCG fall in the processes of the absorption after the instillation of BCG, the internalization of BCG, cytokine release induced by a series of signal transduction pathways, and the effect stage of innate and acquired immune responses. Nonetheless, the limited ascertainments of the mechanism of BCG action cannot fully explain the clinical phenomenon caused by BCG. Therefore, the other mechanisms of BCG action have remained the research hotspot aiming to explore more targeted treatments or to initiate new therapeutic methods avoiding harm. By summarizing the recent research achievements of the mechanism of BCG works on bladder cancer, this review aims to provide clues for researchers to quest more valuable ideas.

Injectable and NIR-Responsive DNA-Inorganic Hybrid Hydrogels with Outstanding Photothermal Therapy.

Surgical excision is one of the main treatments for malignant tumors. However, high risk of tumour recurrence is a major challenge. Near-infrared (NIR)-light-induced tumor photothermal therapy has been studied, while its clinical applications are still restricted due to the limited therapeutic effects. To address this, here, a novel NIR-light-responsive and injectable DNA-mediated upconversion and Au nanoparticle hybrid (DNA-UCNP-Au) hydrogel is developed. Due to the confined and concentrated environment induced by the interaction between adjacent DNA strands and UCNP-Au NPs, an ultrastrong photothermal effect is observed. A photothermal efficiency as high as 42.7% is realized in the hydrogel, which is superior to pristine inorganic particles. Upon direct peritumoral injection of the hydrogel and with the treatment of 808 nm laser irradiation, tumors are eradicated and no recurrence is observed. Meanwhile, there are no side effects on normal tissues due to the local treatment. Taking advantage of the high phototherapeutic effect, biocompatibility, and flexible operability in this system, a novel approach for malignant tumor therapy is demonstrated.

Pro-oncogene Pokemon Promotes Prostate Cancer Progression by Inducing STRN4 Expression.

Pokemon, also known as leukemia/lymphoma-related factor (LRF) is a pro-oncogenic protein highly expressed in several cancers. There have been few in vitro and animal studies about its malignant biological behavior and function, however, its role especially in prostate cancer has not been completely elucidated. Therefore, in this study, we identified that Pokemon is overexpressed in human prostate cancer tissue samples, and its suppression inhibits proliferation of prostate cancer cells, along with promotion of apoptosis. Furthermore, to explore the mechanism by which Pokemon promotes tumor progression, we observed that it binds to the promoter of STRN4 (striatin 4), a downstream target, and subsequently regulates its expression. In conclusion, our study indicated that Pokemon through stimulation of STRN4 expression promotes prostate tumor progression via a Pokemon /STRN4 axis.

Association between androgen receptor gene polymorphisms and testicular germ cell tumor: A systematic review and meta-analysis.

OBJECTIVE: To estimate association between androgen receptor (AR) gene polymorphisms and testicular germ cell tumor (TGCT) susceptibility. MATERIALS AND METHODS: Systematic search of studies on the association between AR gene polymorphisms and TGCT susceptibility was conducted. Odds ratios and 95% confidence intervals were used to pool effect size. RESULTS: For CAG repeat, no evidence was found for association between (>25 vs. ≤25), (>25 vs. 21-25), (<21 vs. 21-25), (others vs. 21-25), (>23 vs. ≤23), (<21 vs. ≥21), (<21 vs. ≥21)'s some subgroups and TGCT susceptibility, which showed stability. In (>24 vs. ≤24), (>24 vs. 21-24), (<21 vs. 21-24), and (others vs. 21-24) and almost all of their subgroups, increased TGCT risk was found without sensitivity analysis. For GGN, no statistical change of TGCT risk was found in (<23 vs. ≥23), (<23 vs. 23), which showed stability. For single nucleotide polymorphism (SNP) rs6152 G > A, rs1204038 G > A and rs2361634 A > G, no statistical change was found without sensitivity analysis. CONCLUSIONS: GGN repeat number <23 may not be associated with TGCTs susceptibility. However, there was insufficient data to fully confirm association in GGN repeat number >23, CAG repeat number, SNP rs6152, rs1204038, and rs2361634.

SPAG9 regulates HEF1 expression and drives EMT in bladder transitional cell carcinoma via rac1 signaling pathway.

Recently SPAG9 has been reported to show aberrant expressions in numerous human malignancies and act as a crucial role in tumor's proliferation and invasion. Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. Due to the diversified function of HEF1, abnormal expression of HEF1 frequently combines with malignant phenotypes and poor prognosis. However, little is known between the relationship of SPAG9 and HEF1 in bladder tumorigenesis. In this study, expression of SPAG9 in vivo and in vitro has been detected by quantitative real-time PCR and Western blot analysis after transfected with SPAG9 overexpression/inhibitor vector. We also found that HEF1 expression shows consistency and is regulated by SPAG9. Overexpression of SPAG9 promotes bladder cancer cells migration through HEF1 upregulation and emerges protein level of activated Rac1. Silencing SPAG9 inhibits cell migration through HEF1 downregulation and reduces protein level of activated Rac1. Also, we found that expression of EMT marker such as E-cadherin, Vimentin is regulated by SPAG9. Considering EMT plays a crucial role in tumor cells spreading and invasion, SPAG9 and HEF1 may potentially set a new therapeutic approach to bladder cancer treatment.

Association between Krüppel like factor 6 intervening sequence 1-27 G > A and cancer susceptibility: A meta-analysis.

BACKGROUND/OBJECTIVE: It has been reported that Krüppel like factor 6 intervening sequence (KLF6 IVS) 1-27 G > A might be associated with cancer susceptibility. Here, we conducted a meta-analysis to summarize and clarify this association. MATERIALS AND METHODS/MAIN RESULTS: A systematic search of studies on the association between KLF6 IVS 1-27 G > A, and cancer susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. Seven articles were included in our meta-analysis. Overall and in prostate cancer, population-based subgroup overall and Caucasian subgroup overall, no evidence was found for the association between KLF6 IVS 1-27 G > A polymorphism and cancer susceptibility in any genetic model and the results showed stability in sensitivity analyses. CONCLUSIONS: KLF6 IVS 1-27 G > A may not be associated with cancer susceptibility, especially the susceptibility of unselected prostate cancer. However, there was insufficient data to fully confirm the association between KLF6 IVS 1-27 G > A and familial prostate cancer, sporadic prostate cancer, gastric cancer, and cancers from different ethnicity, and the results should be interpreted with caution.