Characteristics of changes in plasma proteome profiling after sleeve gastrectomy.

Bariatric surgery (BS), recognized as the most effective intervention for morbid obesity and associated metabolic comorbidities, encompasses both weight loss-dependent and weight loss-independent mechanisms to exert its metabolic benefits. In this study, we employed plasma proteomics technology, a recently developed mass spectrometric approach, to quantitatively assess 632 circulating proteins in a longitudinal cohort of 9 individuals who underwent sleeve gastrectomy (SG). Through time series clustering and Gene Ontology (GO) enrichment analysis, we observed that complement activation, proteolysis, and negative regulation of triglyceride catabolic process were the primary biological processes enriched in down-regulated proteins. Conversely, up-regulated differentially expressed proteins (DEPs) were significantly associated with negative regulation of peptidase activity, fibrinolysis, keratinocyte migration, and acute-phase response. Notably, we identified seven proteins (ApoD, BCHE, CNDP1, AFM, ITIH3, SERPINF1, FCN3) that demonstrated significant alterations at 1-, 3-, and 6-month intervals post SG, compared to baseline. These proteins play essential roles in metabolism, immune and inflammatory responses, as well as oxidative stress. Consequently, they hold promising potential as therapeutic targets for combating obesity and its associated comorbidities.

Tumor Microenvironment Responsive CD8+ T Cells and Myeloid-Derived Suppressor Cells to Trigger CD73 Inhibitor AB680-Based Synergistic Therapy for Pancreatic Cancer.

CD73 plays a critical role in the pathogenesis and immune escape in pancreatic ductal adenocarcinoma (PDAC). AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti-PD-1 therapy, for the treatment of PDAC. Nevertheless, the specific therapeutic efficacy and immunoregulation within the microenvironment of AB680 monotherapy in PDAC have yet to be fully elucidated. In this study, AB680 exhibits a significant effect in augmenting the infiltration of responsive CD8+ T cells and prolongs the survival in both subcutaneous and orthotopic murine PDAC models. In parallel, it also facilitates chemotaxis of myeloid-derived suppressor cells (MDSCs) by tumor-derived CXCL5 in an AMP-dependent manner, which may potentially contribute to enhanced immunosuppression. The concurrent administration of AB680 and PD-1 blockade, rather than gemcitabine, synergistically restrain tumor growth. Notably, gemcitabine weakened the efficacy of AB680, which is dependent on CD8+ T cells. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD-1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC.

Serum Interleukin-6 as a Biomarker for Early Prediction of Post-Operative Infectious Complications After Elective Pancreatectomy.

Background: To investigate whether interleukin (IL)-6 could predict the post-operative complications of elective pancreatectomy early. Patients and Methods: Overall, 122 patients who underwent elective pancreatectomy from June 2020 to May 2021 in our hospital were enrolled. Interleukin-6 was measured on the day before and at six hours after surgery, and on post-operative day one, three, and five. The associations between IL-6 level and post-operative complications were analyzed, and the predictive value of IL-6 for complications was assessed. Results: Sixty-three patients developed post-operative complications. Higher IL-6 was observed in patients with post-operative complications on post-operative day one, post-operative day three, and post-operative day five, with odd ratios of 1.43, 1.68, and 2.54 (p = 0.01, p = 0.01, and p = 0.01), respectively. These trends were also observed in patients with infectious complications preoperatively, on post-operative day one, post-operative day three, and post-operative day five, with ORs of 2.46, 1.95, 2.01, and 2.49 (p = 0.00, 0.00, 0.01, 0.00) respectively. Multivariate regression revealed that IL-6 is the only predictor for infectious complications on post-operative day one (p = 0.016). Based on the optimal cutoffs, pre-operative IL-6, IL-6 on post-operative day one and post-operative day three for predicting infectious complications yielded area under the curve (AUC) of 0.73, 0.70, and 0.70, with high negative predictive value of 82.7%, 92.2%, and of 91.3%, respectively. Conclusions: This study validated the early predictive value of IL-6 on infectious complications after pancreatectomy. Because of the performance of serum IL-6 in predicting infectious complications and high NPV, we endorse that IL-6 could be a potential biomarker for early prediction and antibiotic optimization after pancreatectomy.

The early effects of sleeve gastrectomy on postprandial chylomicron triglycerides during the progression of type 2 diabetes.

BACKGROUND: It remains unclear whether early sleeve gastrectomy (SG) improves postprandial very-low-density lipoprotein (VLDL) as well as chylomicron triglycerides (TGs) in a weight-independent manner in patients with or without type 2 diabetes (DM). Herein we investigated the early effects of SG on postprandial VLDL and chylomicron kinetics. METHODS: A liquid meal test was performed before and after 1 week of SG. The plasma was collected for postprandial triglyceride-rich lipoprotein kinetics analyses, including VLDLs and chylomicrons, isolated by high-speed ultracentrifugation. Lipidomics and metabolomics were used to profile lipid and metabolite compositions of plasma and postprandial chylomicrons. De novo fatty acid synthesis in intestinal epithelial cells treated with chylomicron metabolites was examined using RT-PCR, immunoblotting, and free fatty acid measurement. RESULTS: We found that patients with DM had markedly higher VLDL TGs than patients without DM, and such an increase was still retained after SG. In contrast, SG significantly decreased postprandial chylomicron TGs, but surprisingly, the degree of the reduction in patients with DM was less prominent than in patients without DM, confirmed by untargeted lipidomics analysis. Moreover, 5 unique metabolites potentially linked to de novo fatty acid synthesis from the pathway analysis were discovered by further metabolomic analysis of postprandial chylomicrons from patients with DM who underwent SG and verified by In vitro intestinal epithelial cell culture experiments. CONCLUSIONS: SG in 1 week did not impact postprandial VLDL but decreased chylomicron TGs. Patients with DM keep higher postprandial chylomicron TG concentrations than patients without it after SG, potentially through some unique metabolites that increase intestinal fatty acid synthesis. These results implicate the timing for SG to reach lower intestinal fatty acid synthesis and postprandial chylomicron TG production is prior to the diagnosis of DM to potentially reduce cardiovascular risks.

Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress.

It is well known that neuroinflammation is closely related to the pathophysiology of depression. Due to individual differences in clinical research, the reduction of hippocampal volume in patients with depression is still controversial. In this experiment, we studied a typical kind of tricyclic antidepressant, clomipramine. We designed a series of experiments to find its role in depressive-like behavior, hippocampal neuroinflammation as well as hippocampal volume changes induced by chronic unpredictable mild stress (CMS). Rats exhibited defective behavior and hippocampal neuroinflammation after 12 weeks of CMS, which included elevated expression of cleaved interleukin-1ß (IL-1ß) and NLRP3 inflammasome together with the activation of microglia. Rats exposed to CMS showed weakened behavioral defects, reduced expression of IL-18, IL-6, and IL-1ß along with reversed activation of microglia after clomipramine treatment. This indicates that the antidepressant effect of clomipramine may be related to the reduced expression of NLRP3 inflammasome and cleaved IL-1ß. Moreover, we found an increased hippocampal volume in rats exposed to CMS after clomipramine treatment while CMS failed to affect hippocampal volume. All these results indicate that the NLRP3 inflammasome of microglia in the hippocampus is related to the antidepressant effects of clomipramine and CMS-induced depressive-like behavior in rats.

Acute Effects of Sleeve Gastrectomy on Glucose Variability, Glucose Metabolism, and Ghrelin Response.

PURPOSE: This study aims to examine the changes of glucose metabolism, glucose variability (GV), and ghrelin secretion within 1 week following SG in Chinese patients with obesity. MATERIALS AND METHODS: Forty-nine patients with obesity (15 with type 2 diabetes) were enrolled to undergo SG. Within 1 week before and after surgery, liquid meal tests were performed in all subjects, and continuous glucose monitoring (CGM) was performed in diabetic patients. Blood samples were collected at 0, 15, 30, 45, 60, 120, and 180 min for glucose, C-peptide, insulin, and ghrelin analysis in liquid meal test. Mean amplitude of glucose excursions (MAGE), standard deviations (SD), and percent time-in-range (%TIR) determined by CGM were analyzed. RESULTS: Both in diabetic and non-diabetic groups, significant decrease was observed in glucose, insulin, C-peptide, and ghrelin. Homeostasis model assessment-insulin resistance and liver fat content was decreased. In diabetic group, MAGE and SD were decreased significantly, and the percent time-in-range was higher. The decrease in blood glucose was positively correlated with the decrease in ghrelin concentration in non-diabetic group. CONCLUSION: Within 1 week after SG, both glucose metabolism and glucose variability were improved significantly. Suppression of ghrelin secretion postoperatively might be a driver of this early improved glycemia homeostasis.

Preoperative Thyroid Autoimmune Status and Changes in Thyroid Function and Body Weight After Bariatric Surgery.

BACKGROUND: Bariatric surgery has emerged as the most effective therapy for morbid obesity. There is increasing evidence that bariatric surgery could alleviate systemic inflammation and influence thyroid function. The current study aimed to investigate the associations of preoperative thyroid autoimmune status with the changes in body weight and thyroid function after bariatric surgery. METHODS: We recruited 101 patients with morbid obesity (44 men and 57 women) who received bariatric surgery at Zhongshan Hospital, Fudan University. Those who had used thyroid hormone replacement or antithyroid drugs were excluded. General linear models were used to compare the changes in body weight and thyroid function in participants with different thyroid autoimmune statuses. RESULTS: After bariatric surgery, serum-free triiodothyronine (FT3) (4.94 ± 0.73 vs 4.33 ± 0.59 pmol/L, P < 0.001) and thyroid-stimulating hormone (TSH) (3.13 ± 1.59 vs 2.26 ± 1.26 µIU/mL, P < 0.001) were significantly reduced, accompanied by reductions in BMI (42.1 ± 7.6 vs 31.4 ± 6.5 kg/m2, P < 0.001), and estimated basal metabolic rate (2002 ± 398 vs 1700 ± 336 kcal/day, P = 0.001) and an improvement in lipid profiles. Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels also decreased significantly from 79.3 and 177.1 IU/mL to 57.8 and 66.0 IU/mL in participants with positive thyroid antibodies (P < 0.05). Further analysis showed that the positive preoperative thyroid autoimmune status was associated with less reduction in serum TSH (0.05 ± 1.59 vs - 1.00 ± 1.43 µIU/mL, P = 0.021) and BMI (- 8.3 ± 3.6 vs - 11.0 ± 4.5 kg, P = 0.049) after bariatric surgery. CONCLUSION: Our study highlights a group of patients with morbid obesity, who have positive preoperative thyroid autoimmunity and less reduction in serum TSH levels and body weight after bariatric surgery.

Overexpression of miR-135b-5p promotes unfavorable clinical characteristics and poor prognosis via the repression of SFRP4 in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and malignant neoplasm. The aberrant expression of miR-135b-5p and secreted frizzled-related protein 4 (SFRP4) has been revealed to be involved in various cancers. However, the clinical significance of miR-135b-5p and that of its potential target SFRP4 in PDAC remain to be elucidated. Here, we found that miR-135b-5p was markedly upregulated in pancreatic cancer tissue compared with corresponding adjacent normal tissue, whereas SFRP4 was significantly downregulated. The expression of miR-135b-5p was negatively correlated with the expression of SFRP4. PDAC patients with regional lymph node metastases, vascular invasion, tumor microthrombus and higher PET-CT SUVmax values had significantly higher expression of miR-135b-5p. Immunoblotting revealed that regional lymph node metastases were correlated with expressive states of SFRP4. Negative SFRP4 expression was significantly associated with old age, larger tumor size, regional lymph node metastasis and poor differentiation. Survival analyses demonstrated that miR-135b-5p and SFRP4 could predict outcomes and that miR-135b-5p was an independent predictor. In vitro, the overexpression of miR-135b-5p promoted the migration and proliferation of PANC-1 and MiaPaCa-2 cells, while immunoblotting demonstrated the downregulation of SFRP4 and the upregulation of beta-catenin. Inhibition of miR-135b-5p suppressed migration, induced apoptosis of PANC-1 and AsPC-1 cells, and reduced the expression of beta-catenin. A luciferase reporter assay confirmed that miR-135b-5p repressed the expression of SFRP4 via the direct targeting of its 3'-untranslated regions. In conclusion, the overexpression of miR-135b-5p and the downregulation of SFRP4 were associated with unfavorable clinical characteristics and poor prognosis, and SFRP4 was shown to be a direct downstream target of miR-135b-5p. Thus, the mechanism that underlies the miR-135b-5p-SFRP4-Wnt/beta-catenin axis represents a potential target for PDAC diagnosis and therapy.

[Prevention, diagnosis and treatment of perioperative complications of bariatric and metabolic surgery].

Surgical operation in treating obesity and type 2 diabetes is popularizing rapidly in China. Correct prevention and recognition of perioperation-related operative complications is the premise of ensuring surgical safety. Familiar complications of the operation include deep venous thrombosis, pulmonary artery embolism, anastomotic bleeding, anastomotic fistula and marginal ulcer. The prevention of deep venous thrombosis is better than treatment. The concrete measures contain physical prophylaxis (graduated compression stocking and intermittent pneumatic compression leg sleeves) and drug prophylaxis (unfractionated heparin and low molecular heparin), and the treatment is mainly thrombolysis or operative thrombectomy. The treatment of pulmonary artery embolism includes remittance of pulmonary arterial hypertension, anticoagulation, thrombolysis, operative thrombectomy, interventional therapy and extracorporeal membrane oxygenation (ECMO). Hemorrhage is a rarely occurred but relatively serious complication after bariatric surgery. The primary cause of anastomotic bleeding after laparoscopic gastric bypass is incomplete hemostasis or weak laparoscopic repair. The common bleeding site in laparoscopic sleeve gastrectomy is gastric stump and close to partes pylorica, and the bleeding may be induced by malformation and weak repair technique. Patients with hemodynamic instability caused by active bleeding or excessive bleeding should timely received surgical treatment. Anastomotic fistula in gastric bypass can be divided into gastrointestinal anastomotic fistula and jejunum-jejunum anastomotic fistula. The treatment of postoperative anastomotic fistula should vary with each individual, and conservative treatment or operative treatment should be adopted. Anastomotic stenosis is mainly related to the operative techniques. Stenosis after sleeve gastrectomy often occurs in gastric angle, and the treatment methods include balloon dilatation and stent implantation, and surgical treatment should be performed when necessary. Marginal ulcer after gastric bypass is a kind of peptic ulcer occurring close to small intestine mucosa in the junction point of stomach and jejunum. Ulcer will also occur in the vestige stomach after laparoscopic sleeve gastrectomy, and the occurrence site locates mostly in the gastric antrum incisal margin. Preoperative anti-HP (helicobacter pylorus) therapy and postoperative continuous administration of proton pump inhibitor (PPI) for six months is the main means to prevent and treat marginal ulcer. For patients on whom conservative treatment is invalid, endoscopic repair or surgical repair should be considered. Different surgical procedures will generate different related operative complications. Fully understanding and effectively dealing with the complications of various surgical procedures through multidisciplinary cooperation is a guarantee for successful operation.

microRNA-454 shows anti-angiogenic and anti-metastatic activity in pancreatic ductal adenocarcinoma by targeting LRP6.

Our previous work has shown that microRNA-454 (miR-454) can inhibit the growth of pancreatic ductal adenocarcinoma (PDAC) by blocking the recruitment of bone marrow-derived macrophages. In the present study, we aimed to explore its role in the proliferation, invasion, and pro-angiogenic activity of PDAC cells in vitro and lung metastasis in vivo. PANC-1 and MiaPaCa-2 cells were transfected with a miR-454-expressing plasmid and tested for cell proliferation, colony formation, cell cycle distribution, invasion, and pro-angiogenic activity. The target gene(s) that mediated the action of miR-454 was identified. The effect of miR-454 overexpression on lung metastasis of PDAC was evaluated in nude mice. Of note, overexpression of miR-454 significantly inhibited PDAC cell proliferation and colony formation and arrests PDAC cells at the G2/M phase. Decreased invasiveness was observed in miR-454-overexpressing PDAC cells. Conditioned media from miR-454-overexpressing PANC-1 cells contained lower levels of vascular endothelial growth factor and had reduced capacity to induce endothelial cell tube-like structure formation. Mechanistically, miR-454 was found to target the mRNA of LRP6 and inhibit the activation of Wnt/ß-catenin signaling in PDAC cells. Ectopic expression of LRP6 significantly reversed the suppressive effects of miR-454 on PDAC cells. In vivo studies confirmed that miR-454-overexpressing PANC-1 cells formed significantly less lung metastases than control cells. Altogether, miR-454 functions as a suppressor in tumor growth, angiogenesis, and metastasis in PDAC, likely through downregulation of LRP6.

MicroRNA-454 regulates stromal cell derived factor-1 in the control of the growth of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant carcinoma with an extremely high lethality. We recently reported that hypoxia-inducible factor 1 (HIF-1) targets quiescin sulfhydryl oxidase 1 to facilitate PDAC cell growth and invasion. Here, we analyzed the control of another HIF-1 target, stromal cell derived factor-1 (SDF-1), in PDAC cells. We detected significantly more CD68+ macrophages in the PDAC, compared to normal human pancreas (NT). Since macrophages are recruited to the tissue through their expression of CXCR4 in response to SDF-1, we thus examined the SDF-1 levels in the PDAC specimens. Surprisingly, the SDF-1 protein but not mRNA significantly increased in PDAC, compared to NT. Moreover, a SDF-1-targeting microRNA, miR-454, was found to decrease in PDAC. Promoter luciferase assay confirmed that bindings of miR-454 to 3'-UTR of SDF-1 mRNAs inhibited SDF-1 protein translation. Co-culture of bone marrow derived macrophages and miR-454-modified PDAC cells in a transwell migration experiment showed that macrophages migrated less towards miR-454-overexpressing PDAC cells, and migrated more towards miR-454-depleted cells. Implanted miR-454-depleted PDAC cells grew significantly faster than control, while implanted miR-454-overexpressing PDAC cells grew significantly slower than control. Together, our data suggest that miR-454 may regulate SDF-1 in the control of the growth of PDAC.

Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models.

OBJECTIVES: To investigate the antitumor activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1 in patient-derived pancreatic cancer xenograft mouse models and to explore biomarkers that could predict drug efficacy. METHODS: Ten patient-derived xenograft models were established. The third-generation tumor-bearing mice were randomized into 4 treatment groups: (1) control; (2) S-1; (3) nab-paclitaxel; (4) S-1 plus nab-paclitaxel. Resected tumors were tested by immunohistochemistry for the expression of thymidylate synthase, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), secreted protein that is acidic and rich in cysteine, human epidermal growth factor receptor 2 (HER2), collagen-1, and CD31. RESULTS: Tumor growth inhibition of the S-1 group, nab-paclitaxel group, and combination group was 69.52%, 86.63%, 103.56%, respectively (P < 0.05). The efficacy of S-1 is better in thymidylate synthase-negative, OPRT-positive, and DPD-negative tumors. The efficacy of nab-paclitaxel is better in HER2-positive tumors. Collagen-1 was decreased and CD31 was increased in tumors treated with nab-paclitaxel and S-1 plus nab-paclitaxel compared with control or S-1. CONCLUSIONS: This preclinical study showed that S-1 plus nab-paclitaxel exerted significantly better antitumor activity than S-1 or nab-paclitaxel alone. Thymidylate synthase, OPRT, and DPD were possibly biomarkers of S-1 and HER2 of nab-paclitaxel.

Clinical characteristics and prognostic factors of patients with gastric neuroendocrine carcinoma treated with radical surgery.

BACKGROUND: Gastric neuroendocrine carcinomas (g-NECs) are rare tumors that have aggressive biological behaviors and poor prognosis, but the prognostic factors of postoperative patients with g-NEC are still unclear. Our aim was to study and explore the clinical characteristics and prognostic factors of patients with g-NEC treated with radical surgery. METHODS: The clinical data of 43 g-NEC patients who underwent surgery from January 2002 to January 2011 at the Zhongshan Hospital of Fudan University were analyzed. Follow-up was conducted by telephone, mail, or returning visit survey. RESULTS: The sizes of the 43 neuroendocrine carcinomas (G3) were 1.5 cm × 1.5 cm × 0.5 cm to 7 cm × 8 cm × 1.5 cm. Eight NECs were localized, and 35 had lymph node involvement, of which 1 also had hepatic metastasis. At the end of the follow-up, the follow-up rate was 97.7% (42/43), and the median follow-up time was 22.2 months. The median overall survival of g-NEC patients was 36.5 months, and the 1-, 3-, and 5-year overall survival rates were 86.0%, 51.6%, and 36.7%, respectively. Sex (P < 0.05) and lymph node involvement (P < 0.05) were prognostic factors of postoperative g-NEC patients, among which sex was an independent prognostic factor (P < 0.05), as a survival advantage of female patients over male was observed. CONCLUSIONS: Most of the g-NECs were diagnosed at an advanced stage. The prognosis of g-NECs was related with sex and lymph node involvement, of which sex was an independent prognostic factor, with female patients having a survival advantage.

HIF1 contributes to hypoxia-induced pancreatic cancer cells invasion via promoting QSOX1 expression.

BACKGROUND: Quiescin sulfhydryl oxidase 1 (QSOX1), which oxidizes sulfhydryl groups to form disulfide bonds in proteins, is found to be over-expressed in various pancreatic cancer cell lines and patients. QSOX1 promotes invasion of pancreatic cancer cells by activating MMP-2 and MMP-9. However, its regulatory mechanism remains largely undefined. METHODS: Real-time PCR and Western blot were employed to detect the expression of QSOX1 in human pancreatic cancer cell lines under hypoxic condition. Luciferase reporter and ChIP assays were used to assess the regulation of QSOX1 by hypoxia-inducible factor 1 (HIF-1). Small interfering RNA (siRNA) was applied to knock down endogenous expression of QSOX1. Matrigel-coated invasion chamber essays were conducted to detect the invasion capacity of QSOX1-depleted cells. RESULTS: Both hypoxia and hypoxia mimicking reagent up-regulated the expression of QSOX1 in human pancreatic cancer cell lines. Knockdown of HIF-1α eliminated hypoxia induced QSOX1 expression. HIF-1α was found directly bound to two hypoxia-response elements (HRE) of QSOX1 gene, both of which were required for HIF-1 induced QSOX1 expression. Moreover, QSOX1 silencing blocked hypoxia-induced pancreatic cancer cells invasion. CONCLUSION: QSOX1 is a direct target of HIF-1 and may contribute to hypoxia-induced pancreatic cancer cells invasion.

Associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk: evidence from a meta-analysis.

Glutathione S-transferases (GSTs), including glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), are multifunctional enzymes which play vital roles in the detoxification of a variety of carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 have been implicated in pancreatic cancer risk, but the results of published studies remain conflicting. Thus, a meta-analysis was conducted to estimate the effect of GSTM1 and GSTT1 polymorphisms on the risk of developing pancreatic cancer. A comprehensive search was performed in the PubMed, Embase, Web of Science, and Wanfang databases to identify the available studies on the associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk. The pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) was used to estimate the associations. Stratified analyses by ethnicity and sensitivity analyses were performed to further identify the relationships. Overall, the null genotype of GSTT1 was associated with an increased risk of pancreatic cancer (OR = 1.61, 95 % CI 1.06-2.44, P OR = 0.025), but similar association was not found between the null genotype of GSTM1 and pancreatic cancer risk. Besides, a significant association of GSTT1 polymorphism with pancreatic cancer risk was identified in Asians (OR = 2.58, 95 % CI 1.67-3.98, P OR < 0.001), but not in Caucasians (OR = 1.16, 95 % CI 0.94-1.43, P OR = 0.170). Sensitivity analyses by sequential omission of individual study confirmed the stability of our results. Meta-analysis of available data thus far shows that the null genotype of GSTT1 is a risk factor for pancreatic cancer, particularly in the Asian population. The currently available data are not sufficient enough to identify the association between the GSTM1 polymorphism and pancreatic cancer risk.