Logically derived sequence tandem mass spectrometry for structural determination of Galactose oligosaccharides.

Mass spectrometry has high sensitivity and is widely used in the identification of molecular structures, however, the structural determination of oligosaccharides through mass spectrometry is still challenging. A novel method, namely the logically derived sequence (LODES) tandem mass spectrometry (MSn), for the structural determination of underivatized oligosaccharides was developed. This method, which is based on the dissociation mechanisms, involves sequential low-energy collision-induced dissociation (CID) of sodium ion adducts, a logical sequence for identifying the structurally decisive product ions for subsequent CID, and a specially prepared disaccharide CID spectrum database. In this work, we reported the assignment of the specially prepared galactose disaccharide CID spectra. We used galactose trisaccharides and tetrasaccharides as examples to demonstrate LODES/MSn is a general method that can be used for the structural determination of hexose oligosaccharides. LODES/MSn has the potential to be extended to oligosaccharides containing other monosaccharides provided the dissociation mechanisms are understood and the corresponding disaccharide database is available.

De novo structural determination of oligosaccharide isomers in glycosphingolipids using logically derived sequence tandem mass spectrometry.

Despite the importance of carbohydrates in biological systems, structural determination of carbohydrates remains difficult because of the large number of isomers. In this study, a new mass spectrometry method, namely logically derived sequence tandem mass spectrometry (LODES/MSn), was developed to characterize oligosaccharide structures. In this approach, sequential collision-induced dissociation (CID) of oligosaccharides is performed in an ion trap mass spectrometer to identify the linkage position, anomeric configuration, and stereoisomers of each monosaccharide in the oligosaccharides. The CID sequences are derived from carbohydrate dissociation mechanisms. LODES/MSn does not require oligosaccharide standards or the prior knowledge of the rules and principles of biosynthetic pathways; thus LODES/MSn is particularly useful for the investigation of undiscovered oligosaccharides. We demonstrated that the structure of core oligosaccharides in glycosphingolipids can be identified from more than 500 000 isomers using LODES/MSn. The same method can be applied for determining the structures of other oligosaccharides, such as N-, and O-glycans, and free oligosaccharides in milk.

Automatic Full Glycan Structural Determination through Logically Derived Sequence Tandem Mass Spectrometry.

Glycans have diverse functions and play vital roles in many biological systems, such as influenza, vaccines, and cancer biomarkers. However, full structural identification of glycans remains challenging. The glycan structure was conventionally determined by chemical methods or NMR spectroscopy, which require a large amount of sample and are not readily applicable for glycans extracted from biological samples. Although it has high sensitivity and is widely used for structural determination of molecules, current mass spectrometry can only reveal parts of the glycan structure. Herein, the full structures of glycans, including diastereomers, the anomericity of each monosaccharide, and the linkage position of each glycosidic bond, which can be determined by using tandem mass spectrometry guided by a logically derived sequence (LODES), are shown. This new method provides de novo oligosaccharide structural identification with high sensitivity and has been applied to automatic in situ structural determination of oligosaccharides eluted by means of HPLC. It is shown that the structure of a given trisaccharide from a trisaccharide mixture and bovine milk were determined from nearly 3000 isomers by using 6-7 logically selected collision-induced dissociation spectra. The entire procedure for mass spectrometry measurement guided by LODES can be programmed in a computer for automatic full glycan structure identification.

De novo structural determination of mannose oligosaccharides by using a logically derived sequence for tandem mass spectrometry.

Carbohydrates play important roles in biological recognition processes. However, determining the structures of carbohydrates remains challenging because of their complexity. A simple tandem mass spectrometry-based method for determining the structure of underivatized mannose tetrasaccharides was demonstrated. This method employed the multistage low-energy collision-induced dissociation (CID) of sodium adducts in an ion trap, a logically derived sequence (LODES) from the dissociation mechanism for deciding the sequence of CID, and a specially prepared disaccharide spectrum database. Through this method, the linkages, anomeric configurations, and branch locations of carbohydrates could be determined without the prior assumption of possible structures. We validated this method by blind test of all the commercial available mannose tetrasaccharides. We showed that the structure of a given tetrasaccharide can be determined from 928 isomers by using only three to six appropriately selected CID mass spectra according to the proposed procedure. This method is simple and rapid and has the potential to be applied to other hexoses and oligosaccharides larger than tetrasaccharides. The CID procedures can be built in a computer-controlled mass spectrometer for automatic structural determination of underivatized oligosaccharides. Graphical abstract.

Unexpected Dissociation Mechanism of Sodiated N-Acetylglucosamine and N-Acetylgalactosamine.

The mechanism for the collision-induced dissociation (CID) of two sodiated N-acetylhexosamines (HexNAc), N-acetylglucosamine (GlcNAc), and N-acetylgalactosamine (GalNAc), was studied using quantum-chemistry calculations and resonance excitation in a low-pressure linear ion trap. Experimental results show that the major dissociation channel of the isotope labeled [1-18O, D5]-HexNAc is the dehydration by eliminating HDO, where OD comes from the OD group at C3. Dissociation channels of minor importance include the 0,2A cross-ring dissociation. No difference has been observed between the CID spectra of the α- and ß-anomers of the same HexNAc. At variance, the CID spectra of GlcNAc and GalNAc showed some differences, which can be used to distinguish the two structures. It was observed in CID experiments involving disaccharides with a HexNAc at the nonreducing end that a ß-HexNAc shows a larger dissociation branching ratio for the glycosidic bond cleavage than the α-anomer. This finding can be exploited for the rapid identification of the anomeric configuration at the glycosidic bond of HexNAc-R' (R' = sugar) structures. The experimental observations indicating that the dissociation mechanisms of HexNAcs are significantly different from those of hexoses were explained by quantum-chemistry calculations. Calculations show that ring opening is the major channel for HexNAcs in a ring form. After ring opening, dehydration shows the lowest barrier. In contrast, the glycosidic bond cleavage becomes the major channel for HexNAcs at the nonreducing end of a disaccharide. This reaction has a lower barrier for ß-HexNAcs as compared with the barrier of the corresponding α-anomers, consistent with the higher branching ratio for ß-HexNAcs observed in experiment.

Long-term safety of total knee arthroplasty in patients with chronic kidney disease in Taiwan: A retrospective cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent condition in Taiwan, and the incidence of total knee arthroplasty (TKA) is on the rise. This study aimed to evaluate the postoperative results of patients with different degrees of CKD after TKA, using data from the Taiwan National Health Insurance Research Database. METHODS: The study analyzed 3078 patients who received TKA from 2012 to 2017, equally divided into three groups: none-CKD, mild CKD (without dialysis), and severe CKD (with dialysis). Propensity score matching was used to minimize selection bias. RESULTS: After TKA, there was no significant difference in the risk of debridement surgery for infection between the three groups (adjusted HR of mild CKD: 0.71 95% CI=0.36-1.38, p=0.3073; adjusted HR of severe CKD: 1.14, 95% CI=0.63-2.06, p=0.6616). However, CKD patients requiring dialysis had a significantly higher risk of mortality (adjusted HR: 1.98, 95% CI=1.57-2.50, p<0.001) and readmission within 90days of any causes (adjusted HR: 1.83, 95% CI=1.48-2.26, p<0.001) than non-CKD and mild CKD patients. CONCLUSION: Severe CKD patients needing dialysis after TKA have a higher risk of mortality and readmission rates than that of the non-CKD or mild CKD patients. If the patient is in the early stage of CKD, their prognosis after receiving TKA is expected to be as good as non-CKD patients. LEVEL OF EVIDENCE: IV; well-designed cohort study.

Adverse events from HPV vaccination in Taiwan.

The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12-15 years between 2013 and 2018 in Taiwan's National Immunization Information System and linked them to a registry for beneficiaries in Taiwan's National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013-2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn's disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician's acceptance of HPV vaccine policy.

Risk Factors for Female Breast Cancer: A Population Cohort Study.

BACKGROUND: The incidence of female BC among the Eastern and Southeastern Asian populations has gradually increased in recent years. However, epidemiological studies on the relationship between a sedentary lifestyle and female BC are insufficient. In order to determine the association between this lifestyle and the incidence of female BC, we conducted a population-based cohort study on women in Taiwan. METHODS: We followed a prospective cohort of 5879 women aged 30 years and over enrolled in the 2001 National Health Interview Survey (NHIS), who developed female BC over a period of 72,453 person years, and we estimated the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using the Cox proportional hazards model. RESULTS: RFs associated with female BC incidence included parity (adjusted HR = 0.63; 95% CI: 0.44-0.91), body mass index (adjusted HR = 1.34; 95% CI: 1.04-1.71), and ≥3 h/day spent sitting (adjusted HR = 1.89; 95% CI: 1.08-3.32). The incidence of female BC in participants who sat for ≥3 h/day and consumed sugary drinks was 2.5 times greater than that in those who sat for <3 h/day and did not consume sugary drinks (adjusted HR = 2.51; 95% CI: 1.01-6.23). CONCLUSIONS: The findings of this study indicate that sedentary behavior and sugary drink intake may increase the risk of developing female BC. These are modifiable RFs; therefore, a healthy lifestyle and diet can reduce the incidence of female BC.

Unusual free oligosaccharides in human bovine and caprine milk.

Free oligosaccharides are abundant macronutrients in milk and involved in prebiotic functions and antiadhesive binding of viruses and pathogenic bacteria to colonocytes. Despite the importance of these oligosaccharides, structural determination of oligosaccharides is challenging, and milk oligosaccharide biosynthetic pathways remain unclear. Oligosaccharide structures are conventionally determined using a combination of chemical reactions, exoglycosidase digestion, nuclear magnetic resonance spectroscopy, and mass spectrometry. Most reported free oligosaccharides are highly abundant and have lactose at the reducing end, and current oligosaccharide biosynthetic pathways in human milk are proposed based on these oligosaccharides. In this study, a new mass spectrometry technique, which can identify linkages, anomericities, and stereoisomers, was applied to determine the structures of free oligosaccharides in human, bovine, and caprine milk. Oligosaccharides that do not follow the current biosynthetic pathways and are not synthesized by any discovered enzymes were found, indicating the existence of undiscovered biosynthetic pathways and enzymes.

Secular Trends in Incidence of Esophageal Cancer in Taiwan from 1985 to 2019: An Age-Period-Cohort Analysis.

In Taiwan, the age-standardized incidence of EC, especially esophageal squamous cell carcinoma (ESCC), has increased substantially during the past thirty years. We described the incidence trends of EC from 1985−2019 by an average annual percentage change (AAPC) and age-period-cohort model by using Taiwan Cancer Registry data. Age-period-cohort modeling was used to estimate the period and cohort effects of ESCC and esophageal adenocarcinoma (EAC). The Spearman's correlation coefficient was used to analyze the correlation between age-adjusted incidence rates of EC and the prevalence of risk factors from national surveys. The results showed the incidence rate of ESCC in men (AAPC = 4.2, 95% CI = 3.1−5.4, p < 0.001) increased prominently from 1985−1989 to 2015−2019 while that of EAC in men (AAPC = 1.2, 95% CI = 0.9−1.5, p < 0.001) and ESCC in women (AAPC = 1.7, 95% CI = 1.4−2.1, p < 0.001) increased to a lesser degree. Increased period effects were observed in ESCC in men, ESCC in women, and EAC in men. High correlations were found between the risk factors and the increased birth-cohort effects of ESCC (p < 0.05). To conclude, the incidence of ESCC in both sex and EAC in men increased with statistical significance in recent decades. The increased prevalence of risk factors from approximately 1970−1995 could explain the increased cohort effects of ESCC.

Secular decreasing trends in gastric cancer incidence in Taiwan: A population-based cancer registry study.

BACKGROUND: Gastric cancer remains a leading cause of cancer death worldwide. In Taiwan, gastric cancer is the sixth leading cause of cancer mortality in both males and females. AIM: To evaluate secular trends in gastric cancer incidence according to age, sex, and Helicobacter pylori (H. pylori) treatment in Taiwan. METHODS: In this population-based study, we used the national Taiwan Cancer Registry database. Annual percent changes in incidence rates were used to describe secular trends in incidence rates and sex ratios of gastric cancer in Taiwan. Pearson's product-moment correlation coefficients were used to analyze the correlation between annual age-adjusted incidence rates and the annual number of patients treated with antibiotic therapy for H. pylori infection. RESULTS: The annual percent changes showed continuously decreasing rates of gastric cancer among both males and females. However, the decreasing trends differed by sex, with an annual percent change of -2.58% in males and -2.14% in females. The age-specific incidence rates increased with age. Within the same age group, more recent time periods showed lower incidence rates than greater time periods. Similarly, the sex ratio was lower in later birth cohorts than in earlier birth cohorts. Age-adjusted incidence rates substantially decreased with increasing numbers of patients being treated with antibiotic therapy for H. pylori infection during 2005 to 2016 (r = 0.72). CONCLUSION: We observed steadily decreasing trends with differential sex ratios in the incidence of gastric cancer in Taiwan. These results support H. pylori eradication programs in Taiwan.

Serum interleukin-6 level but not genotype predicts survival after resection in stages II and III gastric carcinoma.

PURPOSE: It has been suggested that interleukin-6 (IL-6) is a prognostic indicator for survival in patients with gastric carcinoma, but this has not been proved using survival analysis. In Asians, the -634G allele is associated with increased IL-6 production. The objective of this study was to evaluate the association between serum IL-6 levels, -634G/C polymorphism, and overall survival after resection for gastric carcinoma. EXPERIMENTAL DESIGN: A total of 155 consecutive patients with gastric carcinoma were evaluated. Serum IL-6 levels were analyzed using an enzyme-linked immunoabsorbent assay. Genotype was determined by PCR and restriction fragment length polymorphism. Serum levels and survival were correlated with genotype and clinicopathologic factors. RESULTS: Age and stage, but not -634G/C genotype, were associated with serum IL-6 levels. The median survival for patients with stage II or stage III gastric carcinoma was 1,418 days in patients with low (< or =13 pg/mL) versus 618 days in patients with high (>13 pg/mL) serum IL-6 levels (P = 0.038). Results of a multivariate analysis showed that serum IL-6 level of >13 pg/mL was a significant predictor of poor survival (hazard ratio, 1.77; 95% confidence interval, 1.07-2.92; P = 0.026). CONCLUSIONS: Serum IL-6 level of >13 pg/mL correlates with tumor progression and is an independent predictor of poor survival after resection. In patients with stage II and III gastric carcinoma, serum IL-6 level is more effective than stage as a prognostic indicator. By measuring IL-6, these patients can be divided into two groups with significant differences in survival. The -634G/C polymorphism is not associated with serum IL-6 level or survival.

The sandwich sign of non-lymphomatous origin.

PURPOSE: To investigate the etiologies of the sandwich sign other than lymphoma. METHOD: The images of 34 patients with sonographic sandwich sign over a 5-year period were retrospectively reviewed. The etiology was based on the pathologic report of mesenteric lymph nodes, or the presence of extensive metastatic disease in case of known advanced primary cancer or disappearance of the sign after specific treatments. RESULTS: Malignancy accounted for the majority of cases (91%), and was divided into non-Hodgkin's lymphoma (50%) and metastatic carcinomas (41%). Mycobacterium tuberculosis infection was diagnosed in a previously healthy patient, and 2 patients with acquired immunodeficiency syndrome had Mycobacterium avium-complex infection. The sandwich sign was 1 of the initial presentations in 11 cases with newly diagnosed malignancies, including 6 cases of non-Hodgkin's lymphoma and 5 cases of metastatic carcinomas. CONCLUSION: Metastatic carcinomas, M. avium-complex, and M. tuberculosis infection may produce the sandwich sign. Searching for etiologies other than lymphoma is important in patients presenting with the sandwich sign.

RANTES-403 polymorphism is associated with reduced risk of gastric cancer in women.

BACKGROUND: Men are more susceptible to gastric cancer (GC) than women. However, the genetic factors associated with the sex difference are not well understood. Chemokines have been shown to modulate tumor behavior, and the sex-specific effect of the chemokine polymorphisms on the host susceptibility to several diseases has been reported. We aimed to determine the role of chemokine polymorphisms on host susceptibility to GC, with special interest on their sex-specific effect. METHODS: A hospital-based case-control study, including 177 patients with GC and 217 age-matched unaffected healthy controls, was performed in three major tertiary care hospitals. Genotyping for regulated upon activation, normal T-cell expressed and secreted (RANTES) -403 A/G and -28 C/G, CC chemokine receptor 5 (CCR5) deletion, and CCR2-V64I was performed using peripheral blood DNA. RESULTS: The RANTES -403 GA and AA genotypes were independently associated with a 2.3-fold reduced risk of developing GC (OR=0.44, 95% CI 0.22-0.90, P=0.025) compared with GG genotype in women, but not in men. The RANTES -28C/G and CCR2-V64I polymorphisms were not associated with different risk of developing GC. The tumor stage, histological features, and survival rate were not different when stratified by RANTES -403 and -28 and CCR2-V64I genotypes. CONCLUSIONS: Our data indicate that women who inherit A allele at RANTES -403 may be at reduced risk of GC.

Prevalence and clinical characteristics of Barrett's esophagus in a Chinese general population.

BACKGROUND: The prevalence of Barrett esophagus (BE) remains elusive in the general populations. GOALS: The purpose of this study was to identify the prevalence and clinical characteristics of BE in a Chinese general population. STUDY: Between June 2003 and December 2006, consecutive subjects were evaluated via upper gastrointestinal endoscopy during a routine health examination. Patients were evaluated for any abnormalities, including endoscopically suspected esophageal metaplasia (ESEM) and erosive esophagitis (EE). Biopsies were attained from patients with ESEM to confirm a diagnosis of BE. The demographic data and endoscopic findings were retrospectively analyzed. RESULTS: Of the 19,812 endoscopies performed, 56 patients (0.28%) were diagnosed with ESEM and 3129 patients (15.7%) with EE. Twelve of the 56 patients diagnosed with ESEM (0.06% of the total number of patients who underwent endoscopy) were confirmed to have BE after histologic analysis of the biopsies. Patients with BE were older than patients without BE (61.6 vs. 51.7 y), and only one of the 12 patients diagnosed with BE (8.3%) reported typical gastroesophageal reflux symptoms. A majority of the BE patients were categorized as short-segment BE (91.7%) and concomitant EE was found in 4 (33.3%). Smoking, alcohol, and metabolic disorders seemed to be associated with the presence of BE and EE. CONCLUSIONS: The prevalence of BE in a Chinese general population was lower than that in other reported studies, particularly in comparison with the studies originating from Western countries. Patients with advanced age and metabolic disorders are risk factors for developing BE.

Simple Approach for De Novo Structural Identification of Mannose Trisaccharides.

Oligosaccharides have diverse functions in biological systems. However, the structural determination of oligosaccharides remains difficult and has created a bottleneck in carbohydrate research. In this study, a new approach for the de novo structural determination of underivatized oligosaccharides is demonstrated. A low-energy collision-induced dissociation (CID) of sodium ion adducts was used to facilitate the cleavage of desired chemical bonds during the dissociation. The selection of fragments for the subsequent CID was guided using a procedure that we built from the understanding of the saccharide dissociation mechanism. The linkages, anomeric configurations, and branch locations of oligosaccharides were determined by comparing the CID spectra of oligosaccharide with the fragmentation patterns based on the dissociation mechanism and our specially prepared disaccharide CID spectrum database. The usefulness of this method was demonstrated to determine the structures of several mannose trisaccharides. This method can also be applied in the structural determination of oligosaccharides larger than trisaccharides and containing hexose other than mannose if authentic standards are available. Graphical Abstract.

Simple Method for De Novo Structural Determination of Underivatised Glucose Oligosaccharides.

Carbohydrates have various functions in biological systems. However, the structural analysis of carbohydrates remains challenging. Most of the commonly used methods involve derivatization of carbohydrates or can only identify part of the structure. Here, we report a de novo method for completely structural identification of underivatised oligosaccharides. This method, which can provide assignments of linkages, anomeric configurations, and branch locations, entails low-energy collision-induced dissociation (CID) of sodium ion adducts that enable the cleavage of selective chemical bonds, a logical procedure to identify structurally decisive fragment ions for subsequent CID, and the specially prepared disaccharide CID spectrum databases. This method was first applied to determine the structures of four underivatised glucose oligosaccharides. Then, high-performance liquid chromatography and a mass spectrometer with a built-in logical procedure were established to demonstrate the capability of the in situ CID spectrum measurement and structural determination of the oligosaccharides in chromatogram. This consolidation provides a simple, rapid, sensitive method for the structural determination of glucose oligosaccharides, and applications to oligosaccharides containing hexoses other than glucose can be made provided the corresponding disaccharide databases are available.

Association of metabolic syndrome with proximal and synchronous colorectal neoplasm.

BACKGROUND & AIMS: Metabolic syndrome and its associated morbidities have become a major public health problem in both developed and developing countries. Insulin resistance, the core mechanism of metabolic syndrome, has been associated with the development of colorectal neoplasm, but the interrelation between metabolic syndrome and colon cancer is rarely addressed. Our study aimed to determine whether metabolic syndrome is associated with the risk and clinical presentation of colorectal neoplasia. METHODS: Consecutive 4277 ethnic Chinese who received complete total colonoscopy and thorough health checkups were enrolled. Both National Cholesterol Education Program's Adult Treatment Panel III and modified Asian criteria were used for defining metabolic syndrome. Logistic regression modeling was used to elucidate the association between colorectal neoplasia and metabolic syndrome. The impact of metabolic syndrome on distribution and number of colorectal neoplasia was also assessed. RESULTS: Of all those enrolled, 27.1% of men and 18.9% of women met the criteria of metabolic syndrome, and 9.8% had colorectal neoplasia. Metabolic syndrome was associated with odds ratio (OR) of 1.35 (95% confidence interval [CI], 1.05-1.73) for colorectal neoplasia. OR was 0.96 (95% CI, 0.67-1.38) for distal lesions, 1.62 (95% CI, 1.14-2.30) for proximal lesions, 2.15 (95% CI, 1.40-3.31) for synchronous lesions, and 2.30 (95% CI, 1.42-3.72) for synchronous lesions located at both sides of colon. CONCLUSIONS: Subjects with metabolic syndrome have a higher risk of colon neoplasia at the proximal colon and synchronous lesions at both sides of the colon. These findings will help future colon cancer screening and prevention in patients with metabolic syndrome.

Clinicopathological significance of MMP-2 and TIMP-2 genotypes in gastric cancer.

AIMS: Single nucleotide polymorphisms in matrix metalloproteinase-2 (MMP-2) -1306 C/T and tissue inhibitor of metalloproteinase-2 (TIMP-2) -418 G/C abolish the Sp-1 binding site and down-regulate expression of these genes. We aim to elucidate the role of MMP-2 and TIMP-2 in clinicopathological manifestations of gastric cancer. METHODS: We enrolled 240 gastric cancer patients and 283 controls. DNA was extracted from peripheral blood leucocytes. MMP-2 and TIMP-2 genotypes were analysed by PCR-direct sequencing and PCR-RFLP method, respectively. RESULTS: MMP-2 and TIMP-2 genotypes were not associated with gastric cancer development. However, patients with MMP-2 -1306 C/C genotype showed higher risk of lymphatic invasion (odds ratio (OR)=2.77, p=0.01) and venous invasion (OR=2.93, p=0.012). TIMP-2 G/G genotype was associated with serosal invasion (OR=1.89, p=0.009), lymph node metastasis (OR=2.19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033). CONCLUSION: Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer.

Loss of imprinting of insulin-like growth factor II is associated with increased risk of proximal colon cancer.

The aim of this study was to determine the clinicopathological features of sporadic colon cancers with loss of imprinting (LOI) of insulin-like growth factor II (IGF-II) in Chinese patients. DNA from peripheral blood leucocytes and RNA from tumours were amplified and then digested with ApaI to determine the LOI status. Of the 316 patients enrolled for analysis, 149 were informative for IGF-II LOI. The positive rate of IGF-II LOI of colon cancer tissue was 47% (70/149) in Chinese patients. Proximal colon (64%) cancers were more likely to have LOI of IGF-II in tumour than distal colon (40.9%) cancers (odds ratio (OR)=2.60, 95% confidence intervals (CI)=1.21-5.56, p=0.014). LOI of IGF-II in tumours was also associated with more advanced diseases (OR=2.90, 95% CI=1.05-8.04, p=0.04). IGF-II LOI is present in high frequency in Chinese colon cancer patients, especially those with proximal cancer.