Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma.
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Adult↗
Biomedical subjects
S Y Leung
Publications and source records attributed to S Y Leung.
Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
Adenocarcinoma↗
Obstructive sleep apnoea in children with Down syndrome.
INTRODUCTION: Children with Down syndrome (DS) are prone to develop obstructive sleep apnoea (OSA) for a combination of reasons, including small upper airway, midfacial hypoplasia, micrognathia and muscular hypotonia. The objective of this study was to compare the prevalence of OSA in DS children, with or without snoring, with snoring children matched for gender, age and weight for height. METHODS: DS children were prospectively recruited from the Hong Kong Down Syndrome Association. All recruited DS children underwent a sleep polysomnography (PSG) in our sleep laboratory. The same number of patients without DS who underwent sleep PSG in the same period were enrolled as controls after they were matched for gender, age and weight for height. OSA was defined as apnoea-hypopnoea index (AHI) greater than 1.5. RESULTS: 22 DS patients and 22 snoring controls completed the overnight PSG. The mean age of DS children and snoring controls was 10.82 +/- 5.93 and 10.27 +/- 5.68 years, respectively. The prevalence of OSA was 59 percent in DS children and 32 percent in snoring controls. Median and interquartile range (IQR) of AHI of DS children (median 1.80, IQR is 0.40 to 7.10) were significantly higher than those of controls (median 0.50, IQR is 0.00 to 2.03, p-value equals 0.041). Out of 13 DS children with OSA, eight of them (61.5 percent) had no habitual snoring. CONCLUSION: 59 percent of DS children in the current series were found to have OSA and they were more likely to develop OSA than controls. Nearly 40 percent of DS children with OSA did not have habitual snoring.
Adolescent↗
Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention-deficit/hyperactivity disorder (ADHD): increased prevalence of the 2-repeat allele.
There is an increased prevalence of the 7-repeat (7R) allele of the dopamine receptor D4 (DRD4) gene in attention-deficit/hyperactivity disorder (ADHD). However, the population prevalence of the 7R allele varies considerably across ethnicity and is very low in Asians. To test whether this 7R allele/ADHD association still held in a Chinese clinical sample, 32 Han Chinese children with a confirmed ADHD diagnosis and normal IQ who were methylphenidate-responders were genotyped. None of them had a DRD4 7R allele. Instead, we observed a significantly increased prevalence of the 2-repeat (2R) allele in this clinical sample (33%) compared to ethnically-matched controls (20%) (chi(2)(1d.f.) = 5.90, P = 0.015). This approximately 1.65-fold increase of the 2R allele in our probands is close to the observed increase of the 7R allele in European-ancestry ADHD children. Recent genetic studies have indicated that the 2R allele in Asians is likely derived from the 7R allele. Further, available biochemical data indicate that both the 2R and 7R protein have blunted responses to dopamine compared to the 4R protein. Based on these results, we propose that the observed increased prevalence of the 2R allele in our Han Chinese ADHD probands is still consistent with the 7R allele hypothesis of ADHD in European-ancestry children. Recent studies have suggested that any variant from the conserved ancestral 4R allele might potentially alter biochemistry/phenotype. We hypothesize that an increased frequency of any non-4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity. The present findings, however, obtained with a small ADHD sample size, should be replicated.
Adolescent↗
BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs.
BACKGROUND: Malignant melanoma arising from different body compartments may be associated with differing aetiological factors and clinical behaviour, and may manifest diverse molecular genetic profiles. Although many studies have focused on cutaneous melanoma, little is known of mucosal and other types of melanoma. In particular, malignant melanoma of soft parts is different from other melanomas in many respects, yet manifests a common melanocytic differentiation. Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients. Few data are available for non-cutaneous melanomas. AIMS: To study the incidence of BRAF and NRAS mutations in melanomas arising in diverse internal organs. METHODS: Fifty one melanomas from various internal organs were investigated for BRAF and NRAS mutation by direct DNA sequencing. RESULTS: BRAF and NRAS mutations were found in two and five mucosal melanomas arising from the aerodigestive and female genital tracts (n = 36). Their occurrence is mutually exclusive, giving a combined mutation incidence rate of 19.4% in mucosal melanomas. Both BRAF and NRAS mutations were absent in malignant melanoma of soft parts (n = 7). BRAF mutation was also absent in uveal melanoma (n = 6), but was seen in two of five cutaneous melanomas. The incidence of BRAF or combined BRAF/NRAS mutations in all non-cutaneous groups was significantly lower than published rates for cutaneous melanomas. CONCLUSION: Each melanoma subtype may have a unique oncogenetic pathway of tumour development, and only a small fraction of non-cutaneous melanomas may benefit from anti-RAF treatment.
Adolescent↗
Aberrant epithelial expression of trefoil family factor 2 and mucin 6 in Helicobacter pylori infected gastric antrum, incisura, and body and its association with antralisation.
AIMS: To determine gastric expression of trefoil family factor 2 (TFF2) and MUC6 in Helicobacter pylori positive and negative subjects, and its association with antralisation at the gastric incisura. METHODS: Gastric biopsies from the antrum, incisura, and body of 76 dyspeptic patients without ulcers were used for the determination of H. pylori infection, histological changes, and epithelial TFF2 and MUC6 expression. RESULTS: In the foveola, the rates of TFF2 and MUC6 immunostaining were greater in H. pylori infected (n = 27) than in uninfected patients (n = 49) at the antrum (59.3% v 4.1% for TFF2 and 63.0% v 4.1% for MUC6; both p < 0.001) and incisura (44.4% v 2.0% for TFF2 and 48.1% v 0% for MUC6; both p < 0.001). In the deeper glands, the rates were also greater in H. pylori infected than in uninfected patients at the incisura (85.2% v 22.4% for both TFF2 and MUC6; p < 0.001). Antral-type mucosa was present at the incisura in 28 of the 76 patients. TFF2 and MUC6 expression in the foveola and deeper glands was significantly associated with antral-type mucosa, independent of H. pylori status. CONCLUSIONS: Helicobacter pylori infection increases the expression of TFF2 and MUC6 in the gastric epithelium. Aberrant TFF2 and MUC6 expression is associated with antralisation of gastric incisura.
Adult↗
The association of E-cadherin expression and the methylation status of the E-cadherin gene in nasopharyngeal carcinoma cells.
Loss of E-cadherin (E-cad) has been associated with progression and poor survival in nasopharyngeal carcinoma (NPC). In this study, we investigated the role of methylation on E-cad inactivation in NPC cell lines, as well as in NPC tissue samples. Using 6 NPC cell lines, we found that methylation of the E-cad 5' CpG island promoter region was correlated with the loss of both mRNA and E-cad protein expression in these cell lines. In addition, using 29 NPC and 10 non-malignant nasopharyngeal samples, we also observed 5' CpG methylation of the E-cad gene in 52% (15 out of 29) NPC samples, but in only 10% (1 out of 10) of the non-malignant nasopharyngeal tissues. Our findings indicate that 5' CpG island methylation of the E-cad gene may play an important part in the inactivation of E-cad in NPC. Our results also suggest that reducing the methylation of the E-cad gene may be a potential therapeutic strategy for NPC.
Blotting, Western↗
A prospective comparison of performance of biopsy forceps used in single passage with multiple bites during upper endoscopy.
BACKGROUND AND STUDY AIMS: A single biopsy is usually obtained for each passage of a biopsy forceps. It was hypothesized that multiple bites per passage might improve the quantity and quality of tissue obtained, without significant artifacts. This hypothesis was tested in a prospective, pathologist-blinded study using different forceps. PATIENTS AND METHODS: Forty consecutive patients who underwent elective upper endoscopy were included. Five different forceps were used in six different ways, varying in the number of bites taken per passage. Two pathologists, who were blinded to the type of biopsy forceps used, evaluated the specimens according to the parameters of maximum weight (mg), size of largest fragment (mm), depth, squash artifact, adequacy, and overall rating. RESULTS: A total of 240 biopsy specimens were obtained. The Microvasive Multibite and Megabite forceps obtained specimens with the maximum weight (P<0.05) and the largest size (P<0.05), respectively. Alligator forceps were able to obtain specimens significantly larger in size than the oval-shaped forceps (P<0.05). The Olympus FB-24K forceps performed best in both the adequacy score and the overall rating score (P<0.05). CONCLUSIONS: Forceps with a needle, or the Multibite forceps, allow more biopsies to be taken per passage and improve the quality of tissues obtained. "Needleless" forceps can be used to obtain two samples per passage through the endoscope that are as good as when only one sample is collected. This approach can save time, and causes no significant damage to the biopsy specimens.
Adolescent↗
Inhibition of proteasome function induced apoptosis in gastric cancer.
The ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines AGS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132. The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. AGS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by the activation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP. Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 in AGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result of release of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53, p21(waf1) and p27(kip1) at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G(1) phase. Our present study suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer.
Adenocarcinoma↗
Early-onset colorectal cancer with stable microsatellite DNA and near-diploid chromosomes.
Colorectal cancer has been described in terms of genetic instability selectively affecting either microsatellite sequences (MIN) or chromosome number and structure (CIN). A subgroup with apparently stable, near-diploid chromosomes and stable microsatellites (MACS) also exists. These distinctions are important, partly because of their value in highlighting different pathways of carcinogenesis, and partly because of their direct relevance to prognosis. Study of early-onset cancer has often proved a fruitful resource for the identification of the nature and function of cancer susceptibility genes. In a study of colorectal cancer with stable microsatellite DNA, we describe 22 early-onset tumours (mean age=33), compared with 16 late-onset tumours (mean age=68). Both groups contained carcinomas with the MACS phenotype, characterized by near diploid DNA content, as defined by flow cytometry, and minimal chromosome arm deletion or amplification (six or less events per genome), determined by comparative genomic hybridization (CGH). Minimal chromosome imbalance correlated strongly with diploid DNA content (P<0.001). The proportion of MACS cancers was significantly greater in early-onset as compared to late-onset tumours (64 vs 13%, P=0.005). Of the chromosome arm imbalances commonly observed in late-onset tumours, only 18q- was observed more than twice amongst the 14 early-onset MACS tumours. Seventy-nine per cent of these MACS tumours were located in the distal colon, and 69% were at advanced clinico-pathological stages (with lymph node or distant metastasis). A positive family history of colorectal or other cancers was elicited in seven patients in the MACS early-onset group, and one additional patient in this group had a metachronous ovarian cancer. The results suggest that MACS cancer may have a genetic basis different from either MIN or CIN, and further studies of these cancers may lead to discovery of new mechanisms of colorectal carcinogenesis and cancer susceptibility.
Aged↗
A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: a founder mutation in the Chinese population.
We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It is well known that alternative splicing is common in hMLH1, which complicates RNA based mutation detection methods. In contrast, large deletions in hMLH1, commonly observed in some ethnic groups, tend to escape detection by exon-by-exon direct DNA sequencing. Here we report the detection of a novel germline 1.8 kb deletion involving exon 11 of hMLH1 in a local hereditary non-polyposis colorectal cancer family. This mutation generates a mRNA transcript with deletion of exons 10-11, which is indistinguishable from one of the most common and predominant hMLH1 splice variants. A diagnostic test based on PCR of the breakpoint region led to the identification of an additional young colorectal cancer patient with this mutation. Haplotype analysis suggests that they may share a common ancestral mutation. Our results caution investigators in the interpretation of alternative splicing and have important implications for the design of hMLH1 mutation detection strategy in the Chinese population.
Adaptor Proteins, Signal Transducing↗
One-week ranitidine bismuth citrate-based triple therapy for the eradication of Helicobacter pylori in Hong Kong with high prevalence of metronidazole resistance.
AIM: To compare 1-week ranitidine bismuth citrate-based (RBC) triple therapy vs. omeprazole-based (O) triple therapy for the eradication of Helicobacter pylori infection in Hong Kong with high prevalence of metronidazole resistance. METHODS: Patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive either: (i) RBCCM: ranitidine bismuth citrate (pylorid) 400 mg, clarithromycin 250 mg and metronidazole 400 mg; or (ii) OCM: omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg, each given twice daily for 1 week. Endoscopy (CLO test, histology and culture) and 13C-urea breath test were performed before randomization and 6 weeks after drug treatment. RESULTS: A total of 180 patients were randomized. H. pylori eradication rates (intention-to-treat, n=180/per protocol, n=166) were 83%/92% for RBCCM and 66%/70% for OCM (P=0.01, intention-to-treat and P=0.001, per protocol, respectively). RBCCM treatment was unaffected by metronidazole susceptibility and achieved a significantly higher eradication rate in metronidazole-resistant cases (89%) than the OCM group (45%, P=0.0064). CONCLUSION: One-week ranitidine bismuth citrate-based triple therapy is significantly better than omeprazole-based triple therapy for the eradication of H. pylori infection, especially in metronidazole-resistant cases. It is an effective regimen for the eradication of H. pylori infection in regions with a high prevalence of metronidazole resistance.
Adult↗
An evaluation of invasive and non-invasive tests for the diagnosis of Helicobacter pylori infection in Chinese.
BACKGROUND: Different tests are available for diagnosing Helicobacter pylori infection. AIM: To compare the most commonly used tests either alone or in combination in Chinese patients with respect to routine clinical use or research purpose. METHODS: A total of 294 consecutive dyspeptic patients without previous H. pylori treatment were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus, for a commercially available CLO-test, an in-house rapid urease test, culture, polymerase chain reaction and histological examination. Patients then received a 13C-urea breath test. The H. pylori status of each patient was determined by a concordance of test results. RESULTS: For routine clinical use, histology (antral plus corpus biopsies) had an accuracy of 100%, whilst the rapid urease test had an accuracy of 99.7%. The 13C-urea breath test was equally reliable, with an accuracy of 94.5%. Combinations of two tests did not confer additional advantage over the most accurate single test. For research purposes, the accuracy of using the criteria of two positives out of three diagnostic tests was 100% and equivocal results were not found. CONCLUSION: Histology with or without a rapid urease test was highly accurate for routine clinical use. Alternatively, the 13C-urea breath test was an equally reliable non-invasive test. The two positives out of three tests approach was highly reliable in predicting H. pylori status of untreated Chinese patients in a research setting.
Biopsy↗
An evaluation of the PyloriTek test for the diagnosis of Helicobacter pylori infection in Chinese patients before and after eradication therapy.
BACKGROUND AND AIM: The PyloriTek Test Kit (a 1-h rapid urease test) was developed for the rapid diagnosis of Helicobacter pylori (H. pylori) during endoscopy. Most studies were performed in Western populations. The aim of this study was to evaluate the PyloriTek test for the diagnosis of H. pylori infection in Chinese population. METHODS: Eligible patients without prior treatment or who had had recent eradication of H. pylori were recruited. During endoscopy, biopsies were taken from the antrum and corpus for an in-house rapid urease test (RUT), histology and for the PyloriTek test (one antral and one corpus biopsy). Results of the PyloriTek test were compared with the gold standard (RUT and histology). RESULTS: Analysis of PyloriTek test results from the antrum alone (101 patients before eradication and 52 patients after eradication) showed a sensitivity, specificity, and accuracy of 96.3, 97.9, and 97.0%, respectively, for cases before eradication, and an accuracy of 100% for cases after eradication. The benefit of an additional body biopsy was marginal and only occurred in the pre-eradication group. CONCLUSION: The PyloriTek test was highly accurate for the diagnosis of H. pylori infection before and after eradication therapy, with a final result available at 1 h, which is unmatched by any invasive test so far. It enhances clinical decision-making by allowing the clinicians or endoscopists to start therapy on the same day of an endoscopy visit. One biopsy from the antrum is highly reliable for this purpose.
Anti-Bacterial Agents↗
Synchronous gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma in association with Helicobacter pylori infection: comparing reported cases between the East and West.
The association of Helicobacter pylori infection with synchronous gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma is rare. Three Chinese patients (M:F = 1:2) who were 71, 58, and 75 yr of age were diagnosed to have gastric adenocarcinoma (2 patients) and gastric lymphoma (1 patient) on endoscopic biopsies. Distal gastrectomy was performed in all of them. Histological study of the three resected specimens revealed synchronous gastric adenocarcinoma and MALT lymphoma. H. pylori infection was found in two patients. A literature search revealed another 29 patients with synchronous tumors in whom H. pylori status was examined. Overall, H. pylori infection was found in 78% of 32 patients. The majority of lymphoma was low grade (75%) and was larger than carcinoma (81%). The majority of carcinoma (65.6%) was early. This suggested lymphoma might develop before carcinoma or the presence of MALT lymphoma might increase the risk of developing carcinoma.
Adenocarcinoma↗
Soluble E-cadherin is a valid prognostic marker in gastric carcinoma.
BACKGROUND: Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS: To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS: Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarcinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS: The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008-1.668) and palliative/conservative treatment (p=0.023, CI 1.038-2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION: Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.
Adenocarcinoma↗
Chromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation.
We have previously reported high-frequency microsatellite instability (MSI-H) and germ-line mismatch repair gene mutation in patients with unusually young onset of high-grade glioma. Some of these patients developed metachronous MSI-H colorectal cancer and conformed to the diagnosis of Turcot's syndrome. Frameshift mutation of TGFbetaRII was present in all the colorectal carcinomas but not in brain tumours. We further characterized the genetic pathways of tumour evolution in these metachronous gliomas and colorectal carcinomas. All MSI-H glioblastomas had inactivation of both alleles of the p53 gene and showed over-expression of the p53 protein while none of the colorectal carcinomas had p53 mutation or protein over-expression. Flow cytometry and comparative genomic hybridization revealed that all glioblastomas were chromosomal unstable with aneuploid DNA content, and with a variable number of chromosomal arm aberrations. In contrast, the colorectal carcinomas had diploid or near-diploid DNA content with few chromosomal arm aberrations. The pattern of chromosomal aberrations in the two organs was different. Loss of 9p was consistently observed in all glioblastomas but not in colorectal carcinomas. Epidermal growth factor receptor amplification was absent in all glioblastomas and colorectal carcinomas. Our results suggest that both the frequency of p53 mutation and its effects differ greatly in the two organs. Following loss of mismatch repair function, p53 inactivation and chromosomal instability are not necessary for development of colorectal carcinoma, but are required for genesis of glioblastoma. Oncogene (2000) 19, 4079 - 4083.
Adenocarcinoma↗
Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients.
The Hong Kong Chinese population has an unusually high incidence of colorectal cancer in the young, suggestive of hereditary susceptibility. To search for a genetic basis for this predisposition, we studied the incidence of microsatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to the Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. By medical record review and personal interview, we searched for distinct clinical features associated with the manifestation of MSI in this group of patients. For patients with MSI tumours, blood was taken for detection of germline mutation in 2 mismatch repair (MMR) genes. MSI was present in 33 tumours from 23 males and 10 females (26.6%). Ongoing mutation analysis has so far identified MMR gene mutations in 8 patients with MSI tumours. The incidence of MSI increased significantly with decreasing age at cancer diagnosis. For patients aged 30 to 49, MSI tumours were located mainly at the proximal colon. However, for exceptionally young patients (<30 years), MSI tumours tended to be at the distal large bowel. This observation suggested a differential activity of the MMR pathway in colorectal carcinogenesis in different age groups. On multivariate analysis, young age at cancer diagnosis, proximal tumour location, a strong family history of colorectal cancer, and a personal history of metachronous cancer were independent predictors for MSI status. This knowledge may have an impact on the management of young colorectal cancer patients and their families.
Adaptor Proteins, Signal Transducing↗