Carcinoma In Asian Population Research Articles

MicroRNA-21 as a potential biomarker for detecting esophageal carcinoma in Asian populations: a meta-analysis.

BackgroundMicroRNA-21 (miR-21) is significantly expressed in a variety of cancers and could be used as a tumor biomarker. However, the results are varied, and no studies on the diagnostic usefulness of miR-21 in Asian esophageal cancer (EC) patients have been published. This meta-analysis was aimed at exploring whether miR-21 can be used as a diagnostic marker and assessing its effectiveness.MethodsThe relevant literature was identified in six main databases: Ovid MEDLINE, PsycINFO, PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. The meta-analysis was carried out using Review Manager 5.4, Meta-Disc 1.4 and STATA 15.1 software. In the end, 987 patients from 12 different studies were included. Quality evaluation of diagnostic accuracy studies 2 (QUADAS—2) was used to examine the risk of bias.ResultsThe pooled sensitivity (SEN) was 0.72 (95% CI [0.69–0.75]), the pooled specificity (SPE) was 0.78 (95% CI [0.75–0.81]), the pooled positive likelihood ratio (PLR) was 2.87 (95% CI [2.28–3.59]), the pooled negative likelihood ratio (NLR) was 0.36 (95% CI [0.31–0.43]), the pooled diagnostic odds ratio (DOR) was 10.00 (95% CI [7.73–12.95]), and the area under the curve 0.82 (95% CI [0.79–0.85]). A Deeks’ funnel plot shows that there was no publication bias (P = 0.99).ConclusionOur findings suggest miR-21 might be the potential biomarker for detecting EC in Asian populations, with a good diagnostic value.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60months, intravesical recurrence occurred in 29.4% (n=48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P>0.05). This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, particularly in Asian populations, and responds poorly to conventional therapy. Subclassification of ESCCs by molecular analysis is a powerful strategy in extending conventional clinicopathologic classification, improving prognosis and therapy. Here we identified two ESCC molecular subtypes in Chinese population using gene expression profiling data and further validated the molecular subtypes in two other independent Asian populations (Japanese and Vietnamese). Subtype I ESCCs were enriched in pathways including immune response, while genes overexpressed in subtype II ESCCs were mainly involved in ectoderm development, glycolysis process, and cell proliferation. Specifically, we identified potential ESCC subtype-specific diagnostic markers (FOXA1 and EYA2 for subtype I, LAMC2 and KRT14 for subtype II) and further validated them in a fourth Asian cohort. In addition, we propose a few subtype-specific therapeutic targets for ESCC, which may guide future ESCC clinical treatment when further validated.

Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk.

In this meta-analysis, we investigated the association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with the risk of renal cell carcinoma. We searched the PubMed and Cochrane Library databases up to July 1, 2017, and included 12 eligible case–control studies in our analysis. The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype were all associated with the risk of renal cell carcinoma in Asian populations. However, methylenetetrahydrofolate reductase (rs1801133 and rs1801131), vitamin D receptor (TaqI and Fok1), and interleukin-16 (rs4778889 and rs11556218) gene polymorphisms were not associated with the risk of renal cell carcinoma. Our study indicates that the vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.

FA08.02: ENHANCED RECOVERY AFTER ESOPHAGECTOMY AND RECONSTRUCTION FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Enhanced recovery after surgery (ERAS) was originally designed and used in colorectal surgery. Recently there were some related reports of its implementation on esophageal cancer surgery, mainly adenocarcinoma. This study is to determine if ERAS can be effectively and safely applied to esophageal squamous cell carcinoma in Asian population. Methods In early 2012, our perioperative management protocol was reinvented and has been implemented thereafter. So two groups of patients were set up and compared. Group A is the patients operated on before 2012, managed by the old protocol. Group B is the patients managed under the new protocol. Their demographics, complications, hospital stay and charges were reviewed and analysed. Results Group A 65 patients. Group B 61 patients. The ventilator days, ICU stay and postoperative stay were statistically shorter in group B. There was no hospital mortality in either groups. No increase of complications was noted in group B. The hospital charges in group B were lower although statistically insignificant. Conclusion The new protocol of perioperative care is safe and effectively enhanced the postoperative recovery after esophagectomy and reconstruction for esophageal squamous cell carcinoma. Table 1. Clinical protocol for group A and B POD, post-operative day; ICU, intensive care unit; TPN, total parenteral nutrition; J-P drain, Jackson-Pratt drain; N/S, normal saline; CVC, central venous catheter; NG, nasogastric tube; OR, operating room; NPO, nil per os; IV, intravenous; PCA, patient control analgesia. Disclosure All authors have declared no conflicts of interest.

Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, particularly in Asian populations, and responds poorly to conventional therapy. Sub-classification of ESCCs by molecular analysis is a powerful strategy in extending conventional clinicopathologic classification, improving prognosis and therapy. Here we identified two ESCC molecular subtypes in Chinese population using gene expression profiling data, and further validated the molecular subtypes in two other independent Asian populations (Japanese and Vietnamese). Subtype I ESCCs were enriched in pathways including immune response, while genes over-expressed in subtype II ESCCs were mainly involved in ectoderm development, glycolysis process and cell proliferation. Specifically, we identified potential ESCC subtype-specific diagnostic markers (FOXA1 and EYA2 for subtype I, LAMC2 and KRT14 for subtype II) and further validated them in a fourth Asian cohort. In addition, we propose a few subtype-specific therapeutic targets for ESCC, which may guide future ESCC clinical treatment when further validated. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81602362 to XG; No. 61571414 to AL), the program for Science and Technology Development in Henan Province (No.162102310391 to XG), the program for Young Key Teacher of Henan Province (No. 2016GGJS-214 to XG), the supporting grants of Henan University (No. 2015YBZR048 to XG; No. B2015151 to XG), the program for Innovative Talents of Science and Technology in Henan Province (No. 18HASTIT048 to XG), and Yellow River Scholar Program (No. H2016012 to XG). The funding bodies were not involved in the study design, data collection, analysis and interpretation of data, or in writing of this manuscript. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: A tissue Arrayer (Beecher, MTA-1) was used to construct the ESCC tissue microarray (TMA) comprising of 166 primary ESCC cases collected from Linzhou Cancer Hospital, Henan, China, between 2010 and 2011, as an independent cohort, which were obtained with Institutional review board approval and a waiver of consent due to the archival nature of the specimens.

Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations

Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations

Increased Numb protein expression predicts poor clinical outcomes in esophageal squamous cell carcinoma patients

ABSTRACTNumb is a protein whose asymmetric segregation during cell division determines cell fate and has numerous functions relevant to multiple fields of study, including developmental neurobiology and cancer biology. Little is known about the role of Numb in esophageal squamous cell carcinoma (ESCC), the predominant histological esophageal carcinoma in Asian populations. In this study, we focused on the expression and biologic functions of Numb in the context of ESCC. From analysis of tissue microarrays with 212 patients, it was found that Numb was significantly upregulated in ESCC tissues compared with corresponding non-cancerous tissues. Kaplan-Meier survival analysis suggests that higher expression of Numb was significantly associated with a high tumor recurrence (p = 0.015) and poor overall post-surgical survival (p = 0.016). Using multiple Cox regression, the expression of Numb was determined to be an independent predictor of poor prognosis. When siRNA was used to knockdown Numb in ESCC cell lines, there was a consistent increase in caspase-3 dependent apoptosis and inhibition of cellular proliferation, as well as downregulation of expression of the cancer stem cell markers Oct-4, SOX-2 and Nanog. In addition, downregulated Numb expression was not significantly associated with the migration of ESCC cells. These results indicate that Numb acts as an oncoprotein and has potential as a novel prognostic biomarker and therapeutic target in ESCC patients.

Significant association of the cytokine variants with head and neck cancer risk: evidence from meta-analysis.

To evaluate the possible relevance of the IL-18-137 G>C (rs187238), IL-18-607 C>A (rs1946518) and IL-4-590 C>T (rs2243250) polymorphisms to the genetic susceptibility of head and neck cancer. Data were retrieved from PubMed, EMBASE, Web of Science and CNKI databases, and the results were independently analysed by two reviewers using Stata 14.0 software. After searching for and assessing the literature, a total of thirteen studies involving 2,959 patients newly diagnosed as head and neck cancer and 3,622 controls from healthy donors were analysed. The results suggested that a strong relationship between patients and healthy controls was observed in the IL-18-137 G>C polymorphism in consistence with the result (CC vs. GG + GC: OR = 1.63, P = 0.004; CC vs. GG: OR = 1.82, P = 0.001). When stratified by cancer type, ethnicity and the source of control samples, significant and elevated risks were obtained in the genetic susceptibility to Asian patients with NPC in all genetic models and in those studies using the PCR-RFLP test method. In addition, comparable results were obtained for the IL-18-607 C>A polymorphism, especially for Asian patients with NPC. It should be a potential association between IL-18 variants and nasopharyngeal carcinoma. Furthermore, IL-18 gene variants might be considered as a critical role in predicting the occurrence of nasopharyngeal carcinoma in Asian population. However, the IL-4-590 C>T polymorphism does not influence the development of head and neck cancer.

Meta-analysis of microRNAs as potential biomarkers for detecting esophageal carcinoma in Asian populations.

An Increasing number of studies in the literature have shown that microRNAs (miRNAs) can be used as early diagnostic markers for esophageal carcinoma (EC), but their conclusions remain controversial. Hence, we performed this meta-analysis to evaluate the diagnostic accuracy of using miRNAs in EC and to provide an experimental basis for early diagnosis of the disease. This meta-analysis included 39 Asian studies from 18 articles, which covered 3,708 EC patients and 2,689 healthy controls. We used a bivariate random-effects model, the chi-square test and the I² test to assess sensitivity and heterogeneity. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of miRNAs for diagnosis of EC in Asians reached 0.798, 0.785, 3.705, 0.257 and 14.391, respectively. Additionally, the area under the summary receiver operating characteristic curve was 0.86. Subgroup analysis based on research country (China vs. Japan), sample types (plasma vs. serum) and miRNAs (single vs. multiple; singly reported miRNAs vs. repeatedly reported miRNAs) showed no significant difference in accuracy of diagnosis for each subgroup. MiRNAs can distinguish EC patients from healthy controls. Blood-based miRNAs have better diagnostic value in detecting EC than saliva-based miRNAs, whereas both serum and plasma are recommended for clinical specimens for miRNA detection.

Overexpression of EMT-inducing transcription factors as a potential poor prognostic factor for hepatocellular carcinoma in Asian populations: A meta-analysis.

Background and ObjectivesThe clinical relevance of epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) progression has been highlighted during the last decade. The zinc finger E-box binding homeobox (ZEB) family, the zinc-finger transcriptional repressor (SNAI) family, and the basic helix-loop-helix transcription factor (Twist) family, known as the prominent EMT-inducing transcription factors (EMT-TFs), played a crucial role in the process of EMT. Here, this meta-analysis aimed to evaluate the prognostic value of EMT-TFs high expression in patients with HCC after hepatectomy.ResultsA total of 10 studies involving 1334 patients were retrieved for analysis, the synthetic date indicated that EMT-TFs overexpression was associated with poor postoperative overall survival (OS) [HR = 1.71; 95% CI: 1.40–2.08; p < 0.00001] in HCC. The subgroup analyses revealed that overexpression of each individual EMT-TF (in addition to ZEB2) tended to be associated with poor OS. Moreover, EMT-TFs overexpression correlated with TNM stage, poor histological differentiation, intrahepatic metastasis and vascular invasion.Materials and MethodsRelevant literature search in the PubMed, Web of Science database and Cochrane Library was performed to retrieve all eligible studies. The pooled hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) were calculated to investigation clinicopathological and prognostic significance of EMT-TFs expression in HCC.ConclusionsEMT-TFs overexpression indicated an unfavorable prognosis in HCC patients following curative resection.

2090662 Shear Wave Elastography - Four Essential Color Map Patterns To Rule Out Breast Malignancy

Shear wave elastography (SWE) is a non-invasive imaging technique which provides quantitative tissue elasticity data on breast lesions in addition to conventional ultrasonography (US). The aims of this study are to define the simple color map patterns to rule out malignancy, and evaluate the relationship between SWE findings and biological features of the breast carcinoma in Asian population. This is a retrospective, single center study which included 103 women (age range, 21-91 years) with 104 solid breast lesions identified during routine US performed between June 2013 and May 2014. All breast lesions were subsequently confirmed either by cytological or histological examinations. Obtained SWE images were classified into four patterns: No color on elastography image (pattern 1), vague longitudinal artifact inside the lesion (pattern 2), positive findings only at the surrounding area (pattern 3), and positive findings both at the boundary and inside the lesion (pattern 4). Eligible lesions were then evaluated for the mean quantitative elasticity values in regions of interest (ROI) placed over the stiffest area and the fat area to obtain the tumor/fat SWE ratio (TFSWR). Among the 104 lesions, 44 were malignant and 60 were benign. Color map patterns 1, 2, 3, and 4 were observed in 32, 19, 18, 35 cases respectively. Both patterns 1 and 2 lesions were 100% benign, whereas patterns 3 and 4 included 72% and 89% malignancies respectively. The results for combined US and SWE yielded 100% sensitivity, 85% specificity, 83% positive predictive value, 100% negative predictive value. The mean TFSWR was 18.4±9.7 vs 3.2±5.8 (p<0.001) for malignant and benign lesions. No malignant lesion showed TFSWR of higher than 5, whereas 9 (15%) benign lesions were present within. The TFSWR and hormone receptor status, HER2 status, histological grade, invasive size, lymph node status were not statistically relevant. In addition to conventional US, SWE color map patterns of 1 and 2, and TFSWR of less than 5 excluded all the breast malignancies. SWE results were not associated with any of the biological features of breast carcinoma in Asian population.

Matrix metalloproteinase-1 (MMP1) polymorphism is associated with lowered risk of nasopharyngeal carcinoma in Asian population.

Data on the association between -1607 1G > 2G polymorphism in the promoter region of matrix metalloproteinase-1 (MMP1) and nasopharyngeal carcinoma (NPC) are conflicting. The aim of this study was to confirm whether this polymorphism was a causative factor of NPC. We searched PubMed, Embase, and China National Knowledge Infrastructure (CNKI) for studies on the present topic. A total of four publications (1,044 NPC patients and 1,284 healthy control subjects) were included and meta-analysis was performed to assess the association between -1607 1G > 2G polymorphism and NPC risk. Odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated for 1G1G versus 2G2G, 1G1G + 1G2G versus 2G2G, 1G1G versus 1G2G + 2G2G, 1G versus 2G, and 1G2G versus 2G2G contrast models. Meta-analysis results showed significantly reduced risk of NPC associated with the 1G1G versus 2G2G, 1G versus 2G and 1G2G versus 2G2G contrast models (OR = 0.61, 95 % CI 0.49-0.77; OR = 0.78, 95 % CI 0.65-0.92; OR = 0.86, 95 % CI 0.74-0.99, respectively). When we continued to perform subgroup analysis by ethnicity, the significant association persisted in Asian population and was most pronounced under the 1G2G versus 2G2G model (OR = 0.85, 95 % CI 0.73-0.99). These data suggested that MMP1 -1607 1G > 2G polymorphism was associated with reduced risk of NPC, particularly in the population of Asian descent.

Cyclin D1 Overexpression Is Associated with Poor Clinicopathological Outcome and Survival in Oral Squamous Cell Carcinoma in Asian Populations: Insights from a Meta-Analysis

BackgroundThe clinicopathological significance of cyclin D1 overexpression and prognosis of oral squamous cell carcinoma has not been fully quantified. We performed a comprehensive meta-analysis for evaluation of cyclin D1 overexpression in oral squamous cell carcinoma to determine the strength of this association.MethodsUsing both medical subheadings and free terms, we searched PubMed, Embase and the Institute for Scientific Information Web of Science for all eligible studies published before Nov. 2013. We retrieved 1674 citations, determining that 15 met the selection criteria. We used the odds ratio (OR) and hazard ratio (HR) as the common measures of association to quantitatively determine the correlation between cyclin D1 overexpression and outcomes of oral cancer. We performed a meta-analysis and heterogeneity, sensitivity, and subgroup analyses to clarify and validate the pooled results.ResultsThe pooled results provided compelling evidence that cyclin D1 overexpression was significantly correlated with increased tumor size (OR = 1.617, 95% confidence interval [CI] = 1.046–2.498, p = 0.031), lymphoid node metastasis (OR = 2.035, 95% CI = 1.572–2.635, p<0.001), tumor differentiation (OR = 1.976, 95% CI = 1.363–2.866, p<0.001), and advancement of clinical stages (OR = 1.516, 95% CI = 1.140–2.015, p = 0.004), and adversely influenced overall survival of OSCC patients (HR = 1.897, 95% CI = 1.577–2.282, p<0.001). The strength of association varied in different oral cavity subsites.ConclusionOur findings indicated that cyclin D1 expression correlates with detrimental clinicopathological outcome and poor prognosis in oral squamous cell carcinoma. Our results may be useful in the management of oral cancer.

Relationship between RUNX3 methylation and hepatocellular carcinoma in Asian populations: a systematic review.

Runt-related transcription factor 3 (RUNX3) is a potential tumor suppressor that is frequently hypermethylated in hepatocellular carcinoma (HCC). The present meta-analysis of case-control studies was carried out to determine whether RUNX3 hypermethylation is associated with HCC. The PubMed, Embase, and Chinese National Knowledge Infrastructure databases were searched for all relevant studies published between May 2000 and May 2012. A total of 11 studies were identified, and 8 studies involving 491 patients with HCC and 409 patients without tumors were found to satisfy the inclusion criteria for the meta-analysis. All tissue samples were from Asian populations. There was significant heterogeneity between the studies. Over the entire sample, the odds ratio (OR) of RUNX3 promoter methylation was 18.5 [95% confidence interval (CI), 11.6-29.6] for HCC tissues relative to control tissues. The ORs of RUNX3 methylation were 16.6 (95%CI = 6.5-42.4) for tumor tissues relative to tumor-adjacent tissues in patients with HCC, 67.3 (95%CI = 13.0-348.5) for tumor tissues from patients with HCC relative to liver tissues from patients with non-neoplastic liver diseases, and 3.26 (95%CI = 1.54-6.90) for tissues from patients with hepatitis C virus (HCV)- related HCC relative to liver tissues from patients with HCC unrelated to HCV. There was no association between RUNX3 methylation and age, gender, pathological stage, or hepatitis B virus infection in HCC tissues. Methylation of the RUNX3 promoter strongly correlated with HCC in Asian populations, especially in individuals with HCV-related HCC, and may be a useful marker for HCC diagnosis in these populations.

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95 % confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95 % CI 1.19-1.85, P = 0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1-GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105 val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.

Systematic Review on Epstein-Barr Virus (EBV) DNA in Diagnosis of Nasopharyngeal Carcinoma in Asian Populations

To conduct a meta-analysis to investigate the value of EBV DNA in diagnosis of nasopharyngeal cancer (NPC) in Asian populations, and provide important evidence for screening. Prospective or respective case-control or cohort studies regarding the detection role of EBV DNA for NPC were included in our study. We conducted a comprehensive literature search in PubMed, EMBASE, and the Chinese Biomedical Database (CBM database between January 1980 and March 2012. A total of 18 studies with 1492 NPC cases and 2641 health controls were included. Almost of the included studies were conducted in China, and only one other conducted in Thailand. The overall results demonstrated that the pooled sensitivity, specificity, positive likelihood (+ LR) and negative likelihood (-LR) were 0.73 (0.71-0.75), 0.89 (0.88-0.90), 8.84 (5.65-13.84) and 0.19(0.11-0.32), respectively. The overall EBV DNA detection showed the largest area of 0.932 under the summary receiver operator curve (SROC). The accuracy of detection by plasma for NPC (0.86) was higher than in serum (0.81), with largest areas under the SROC of 0.97 and 0.91, respectively. Our results demonstrated the EBV DNA detection in plasma or serum has high sensitivity and specificity in diagnosis of NPC, especially in Chinese populations with a high risk of cancer.

Novel germline BRCA1 mutations detected in women in singapore who developed breast carcinoma before the age of 36 years.

In recent years, although BRCA1 has been extensively investigated, the contribution of inherited BRCA1 mutations to breast carcinoma in Asian populations is largely unknown. The authors undertook this study to determine the prevalence and spectrum of germline BRCA1 mutations among women in Singapore with early onset breast carcinoma. Forty-three of 72 eligible patients whose breast carcinoma was diagnosed before the age of 36 years were studied, independent of family history. DNA samples from 50 unrelated individuals randomly selected from the National Thalassemia Registry served as controls. Mutational screening was performed by single-strand conformation polymorphism analysis and protein truncation test, and alterations were confirmed by sequencing. First-degree relatives of patients with definite BRCA1 mutations were offered screening. A total of 6 novel alterations in BRCA1 were identified, including 2 frameshift mutations in exon 11 (2846insA and 2885delA), 3 rare sequence variants, and 1 polymorphism. Three women (7%) carried deleterious mutations, and the mutation was present in at least 1 unaffected first-degree relative of the proband. The same mutation (2846insA) was identified in 2 of the 7 unrelated subjects of Malay ethnicity. One mutation and three rare variants were identified in four women with no family history of breast or ovarian carcinoma whereas all women with affected first-degree relatives did not harbor BRCA1 mutations. No mutation was identified in the controls. The spectrum of germline BRCA1 mutations among the patients in this study was distinct from that in Caucasian populations although a similar prevalence was observed. Larger studies are necessary to clarify the significance of the mutation 2846insA in the Malay community and the penetrance of specific mutations in the Singapore population.