Cytomegalovirus, Epstein-Barr virus and risk of breast cancer before age 40 years: a case-control study

We investigated whether there is an association between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) IgG levels and risk of breast cancer before age 40 years. CMV and EBV IgG levels were measured in stored plasma from 208 women with breast cancer and 169 controls who participated in the Australian Breast Cancer Family Study (ABCFS), a population-based case-control study. CMV and EBV IgG values were measured in units of optical density (OD). Cases and controls did not differ in seropositivity for CMV (59 and 57% respectively; P=0.8) or EBV (97 and 96% respectively; P=0.7). In seropositive women, mean IgG values were higher in cases than controls for CMV (1.20 vs 0.98 OD, P=0.005) but not for EBV (2.65 vs 2.57 OD, P=0.5). The adjusted odds ratios per OD unit were 1.46 (95% CI 1.06-2.03) for CMV IgG and 1.11 (0.93-1.33) for EBV IgG. The higher mean CMV IgG levels found in women with breast cancer could be the result of a more recent infection with CMV, and may mean that late exposure to CMV is a risk factor for breast cancer.     

Evaluation Frequency of Merkel Cell Polyoma,Epstein-Barr and Mouse Mammary Tumor Viruses in Patients with Breast Cancer in Kerman,Southeast of Iran

Breast cancer is the most common cancer among women worldwide. Roles of the Epstein-Barr, Merkelcell polyoma and mouse mammary tumor viruses in breast carcinogenesis are still controversial although anyrelationship would clearly be important for breast cancer etiology, early detection and prevention. In the presentstudy associations between EBV, MMTV and Merkel cell polyoma virus and breast cancer in 100 Iranian patientswere evaluated using paraffin-embedded tissues. EBER RNA and expression of p53 and large T antigen wereevaluated by real time PCR and CD34, p63, HER2, PR and ER markers were studied by immunohistochemistry.EBV was detected in 8/100 (8%), MMTV in 12/100 (12%), MPy in 3/100 (3%) and EBER RNA in 18/100 (18%)cases. None of the control samples demonstrated any of the viruses. p53 was suppressed in EBV, MPy and MMTVpositive samples. The large T antigen rate was raised in MPy positive samples. Our results showed that EBV,MMTV and the Merkel cell polyoma virus are foundwith some proportion of breast cancers in our patients,suggesting that these viruses might have a significant role in breast cancer in Kerman, southeast of Iran .     

Colorectal Cancer Trends in Kerman Province,the LargestProvince in Iran,with Forecasting until 2016

Colorectal cancer is one of the most common cancers. The aim of this study is determination its trends inKerman province and individual cities separately until year 2016. This analytical and modeling study was basedof cancer registry data of Kerman University of Medical Sciences, collected during 2001-2010. Among 20,351cancer case, 792 were colorectal cancer cases in age group 18-93 years with a mean of 59.4 and standard deviationof 15.1. By applying time series and data trends, incidences were predicted until 2016 for the province and eachcity, with adjustment for population size. In colorectal cases, 413 (52%) were male, and 379 (48%) were female.The annual increasing rate in Kerman province overall was and can be expected to be 6%, and in the cities ofthe province Rafsanjan, Bardsir, Bam, Kerman, Baft, Sirjan, Jiroft, Kahnuj and Manujan had an increasingrange from 5 to 14% by the year 2016. But in Ravar, Zarand and Shahrbabak reduction in rates of at least 2%could be predicted. The time series showed that the trend of colorectal cancer in female will increase 15% andin male 7% by year 2016. Given the trend of this cancer is increasing so that resources will be consumed in thetreatment of the patients, efforts shoudlbe focused on prevention and early diagnosis of the disease. Screeningcould have an important role leading to improved survival.     

Case–case comparison of smoking and alcohol risk associations with Epstein–Barr virus‐positive gastric cancer

Helicobacter pylori is the primary cause of gastric cancer. However, monoclonal Epstein–Barr virus (EBV) nucleic acid is also present in up to 10% of these tumors worldwide. EBV prevalence is increased with male sex, nonantral localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer, we organized an international consortium of 11 studies with tumor EBV status assessed by in situ hybridization. We pooled individual‐level data on 2,648 gastric cancer patients, including 184 (7%) with EBV‐positive cancers; all studies had information on cigarette use (64% smokers) and nine had data on alcohol (57% drinkers). We compared patients with EBV‐positive and EBV‐negative tumors to evaluate smoking and alcohol interactions with EBV status. To account for within‐population clustering, multilevel logistic regression models were used to estimate interaction odds ratios (OR) adjusted for distributions of sex (72% male), age (mean 59 years), tumor histology (56% Lauren intestinal‐type), anatomic subsite (61% noncardia) and year of diagnosis (1983–2012). In unadjusted analyses, the OR of EBV positivity with smoking was 2.2 [95% confidence interval (CI) 1.6–3.2]. The OR was attenuated to 1.5 (95% CI 1.01–2.3) by adjustment for the possible confounders. There was no significant interaction of EBV status with alcohol drinking (crude OR 1.4; adjusted OR 1.0). Our data indicate the smoking association with gastric cancer is stronger for EBV‐positive than EBV‐negative tumors. Conversely, the null association with alcohol does not vary by EBV status. Distinct epidemiologic characteristics of EBV‐positive cancer further implicate the virus as a cofactor in gastric carcinogenesis.     

Determination of Frequency of Epstein-Barr Virus in Non-Hodgkin Lymphomas Using EBV Latent Membrane Protein 1 (EBV-LMP1) Immunohistochemical Staining

Background: The presence of Epstein-Barr virus (EBV) in Non-Hodgkin’s lymphoma can be identified byimmunohistochemistry for detection of EBV latent membrane protein (LMP). The role of EBV as an etiologic agentin the development of non-Hodgkin lymphoma has been supported by detection of high levels of latent membraneprotein 1 (LMP-1) expression in tumors. However, no study has been conducted in a Pakistani population up tillnow to determine the frequency of Epstein-Barr virus positivity. The objective of our study was to determine avalue for non-Hodgkin lymphoma patients using EBV LMP-1 immunostaining in our institution. Materials andMethods: This study was carried out at the Department of Histopathology, Armed Forces Institute of Pathology(AFIP), Pakistan from December 2011 to December 2012. It was a cross sectional study. A total of 71 patientswho were diagnosed with various subtypes of NHL after histological and EBV LMP-1 immunohistochemicalevaluation were studied. Sampling technique was non-probability purposive. Statistical analysis was achievedusing SPSS version 17.0. Mean and SD were calculated for quantitative variables like patient age. Frequenciesand percentages were calculated for qualitative variables like subgroup of NHL, results outcome of IHC forEBV and gender distribution. Results: Mean age of the patients was 53.6±16 years (Mean±SD). A total of 50(70.4%) were male and 21 (29.6%) were female. Some 9 (12.7%) out of 71 cases were positive for EBV–LMP-1immunostaining, 2 (22.2%) follicular lymphoma cases, 1 (11.1%) case of T-cell lymphoblastic lymphoma, 4 (44.4%)cases of diffuse large B cell lymphomas, 1 (11.1%) mantle cell lymphoma and 1 (11.1%) angioimmunoblastic Tcell lymphoma case. Conclusion: In our study, frequency of EBV in NHL is 12.7% and is mostly seen in diffuselarge B cell lymphoma. This requires further evaluation to find out whether this positivity is due to co-infectionor has a role in pathogenesis.     

Frequency of Epstein Barr Virus Type 1 Among Nasopharyngeal Carcinomas in Iranian Patients

Background: Around 95% of the world’s population are infected with the Epstein-Barr virus (EBV), which can persist latent in B lymphocytes and epithelial cells life-long. EBV has been linked with lymphoid and epithelial cancers and persistence of EBV infection in lymphoid or epithelial cells may result in virus-associated B-cell tumors or nasopharyngeal carcinomas (NPC). This study was conducted to determine the frequency of EBV DNA in nasopharyngeal carcinoma tissue of Iranian patients. Materials and methods: A total of 50 blocks of formalin-fixed paraffin-embedded tissue of NPCs from 38 (76 %) male and 12 (24%) female patients were collected from archives of Ahvaz hospitals. Sections were cut at 5 μm and DNA was extracted for detection of EBV DNA and EBV typing by mested PCR. DNA sequencing was performed to confirm PCR results. The distribution of EBV DNA was compared among WHO histological subtypes of NPC. Results: Some 3 female and 11 (22%) male NPC samples showed positive for EBV DNA type 1, 2/14(22.2%)WHO histological type II and 12/41(29.3%) WHO histological type III. Conclusions: The frequency of EBV DNA among NPCs in Iranian patients was found to be 28%, EBV type I predominating. Both WHO histological type II and III NPC subtypes demonstrated approximately the same detection prevalence.     

p73 gene promoter methylation in Epstein-Barr virus-associated gastric carcinoma

To clarify the significance of p73 in Epstein-Barr virus (EBV)-associated gastric carcinoma (GC), the immunohistochemical expression and CpG-island methylation of p73 were evaluated in cancer tissues and adjacent nonneoplastic tissues of GC with and without EBV infection. Loss of p73 expression by immunohistochemistry was specific to EBV-associated GC (11/13) compared to EBV-negative GC (3/38), which was independent of abnormal p53 expression. With methylation-specific polymerase chain reaction (MSP), the aberrant methylation of p73 exon 1 was similarly specific to EBV-associated GC (12/13), and also rare in EBV-negative GC (2/38). Bisulfite sequencing for p73 exon 1 and its 5' region confirmed the MSP results, showing uniform and high-density methylation in EBV-associated GC. Comparative MSP analysis of p14, p16 and p73 methylation, using 20 cases each of formalin-fixed and paraffin-embedded tissues of early GC with and without EBV infection, confirmed 2 types of methylation: global methylation with increased rates (p14 and p16) and specific methylation of p73 in EBV-associated GC. In nonneoplastic mucosa, p14, p16 and p73 methylation occurred in both EBV-associated (8/33, 6/34 and 3/38, respectively) and EBV-negative GC (6/23, 4/35, and 1/35). p73 methylation was observed in the mucosa without H. pylori infection in all 4 samples. Loss of p73 expression through aberrant methylation of the p73 promoter occurs specifically in EBV-associated GC, together with the global methylation of p14 and p16. A specific type of gastritis, prone to a higher grade of atrophy and p73 methylation, may facilitate the development of EBV-associated GC.     

Human herpes viruses in non-melanoma skin cancers

We examined the possible involvement of human herpes viruses in sporadic non-melanoma skin cancer of Greek patients. Polymerase chain reaction (PCR) based detection assays were utilized for the detection of viral cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) genomes in 24 squamous cell carcinomas (SCC), five Bowen's disease, 72 basal cell carcinomas (BCC) specimens and eight premalignant lesions. Forty-two of 109 (38.5%) skin lesions were found positive for CMV DNA. The highest incidence was 6/8 (75%) observed in specimens with premalignant lesions. The incidence was 37.5% (27/72) in BCC, 33% (8/24) in SCC and 20% (1/5) in extragenital Bowen's disease. All samples were negative for HSV-1/2 and EBV DNA as assessed by our PCR based assay. The CMV infection showed no statistically significant correlation with the histological type, age, site of lesion or sex. Our results give a strong indication of the possible involvement of CMV in non-melanoma skin cancer development.     

Cytomegalovirus reactivation and its clinical impact in patients with solid tumors

Cytomegalovirus reactivation can be life threatening. However, little evidence on its incidence in solid cancers is available. Therefore our single center Cytomegalovirus polymerase chain reaction database with altogether 890 CMV positive blood serum samples of mainly hematological and oncological patients was retrospectively analyzed to examine the occurrence of Cytomegalovirus reactivation in patients with solid tumors, resulting in 107 patients tested positive for Cytomegalovirus reactivation. Seventeen patients with solid cancer and a positive CMV-PCR test were identified, of which eight patients had clinically relevant CMV disease and received prompt antiviral treatment. Five patients fully recovered, but despite prompt antiviral treatment three patients died. Among these three patients two had significant co-infections (in one case EBV and in the other case Aspergillus) indicating that that CMV reactivation was at least one factor contributing to sepsis. The patient with the EBV co-infection was treated in an adjuvant therapy setting for breast cancer and died due to Cytomegalovirus and Epstein-Barr virus associated pneumonia despite intensive therapy. The other two patients had progressive disease of an underlying pancreatic cancer at the time of CMV diagnosis. One patient died due to attendant uncontrollable Aspergillus pneumonia, the other patient most likely died independent from CMV disease because of massively progressive underlying disease.Cytomegalovirus reactivation and disease might be underestimated in routine clinical practice. In our retrospective analysis we show that approximately 50 % of our patients suffering from solid cancers with a positive Cytomegalovirus polymerase chain reaction also had clinically relevant Cytomegalovirus disease requiring antiviral therapy.     

The Presence of Human Papillomavirus and Epstein-Barr Virus Infection in Gastric Cancer: A Systematic Study

Background and Aim: Gastric cancer (GC) is one of the most common infection-related malignancies worldwide. Human Papillomavirus (HPV) and Epstein-Barr virus (EBV) are among the most important viruses affecting many people worldwide. The potential role of these viruses in gastric tissue may explain the possibility of GC, as seen in Helicobacter pylori (H. pylori). This study aimed to systematically investigate the presence of HPV and EBV in GC. Methods: According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, this study is a systematic review based on reported cases. The keywords HPV, EBV and GC, were searched in PubMed, Web of Science, Scopus, EMBASE and Google scholar databases from 2012 to 2022. Articles were selected and evaluated by five researchers independently. The odds ratio of HPV and EBV viruses in GC was estimated. Data analysis was performed by SPSS (Version 20) software. Results: Sixty studies with 14949 patients were included in the study after obtaining the inclusion criteria. The mean prevalence of HPV and EBV viruses in GC was 10.58% and 8.58%, respectively. The highest prevalence of HPV and EBV were 37.74% and 44.44% in Turkey and Iraq, respectively. The highest odds of HPV and EBV in GC were observed in Asia (17.54%) and Africa (19.02%), respectively. Conclusion: The findings indicate the presence of HPV and EBV in GC in the study areas. However, the present study’s results are insufficient for a more accurate conclusion. Therefore, further studies are necessary for the conclusion in this regard.     

四川北部地区肺癌病人GSTM1基因多态性分析

 【摘要】　目的　分析中国四川北部地区汉族肺癌人群谷胱苷肽硫转移酶M1（GSTM1）基因多态性。方法　采用聚合酶链反应（PCR）技术检测该地区125例肺癌患者GSTM1基因缺失频率,并与文献报道的其他地区人群及人种进行比较。结果　中国四川北部地区肺癌患者GSTM1纯合缺失基因型58.4 %（73／125）,其中纯和缺失率女性为62.5 %（20／32）,男性为56.9 %（53／93）;鳞状细胞癌56.1 %（32／57）,腺癌54.8 %（17／31）。与国内外文献报道比较,中国四川北部地区肺癌患者GSTM1基因缺失频率略高于欧美,但仅与土耳其、巴西非裔美国人和印度北部人群差异有统计学意义（P＜0.05）,与国内人群相近（P＞0.05）。结论　中国四川北部地区汉族肺癌人群GSTM1基因多态性未呈现显著的地域和人种特征。     

Sentinel lymph node biopsy in male breast cancer patients.

The concept of sentinel node biopsy has been validated for female breast cancer patients whereas, ALND remains the standard of care for male breast cancer patients with similar tumours. We evaluated the results of SLN biopsy in male breast cancer patients with clinically negative axillae. This study included all male breast cancer patients who underwent SLN biopsy between February 1998 and October 2003. All patients had negative axillae on clinical examination. All patients underwent pre-operative lymphoscintigraphy. SLN biopsy was performed using a combination of Patent blue V and 99mTc-radiolabelled colloidal albumin injected peritumourally. Nine patients, 26-79 years of age, were included in the study. Pre-operative lymphoscinitgraphy identified SLNs in all patients. Intraoperatively, SLNs were successfully localised in all patients. The mean number of SLNs encountered was 2.4. Five patients had a positive SLN, four a negative SLN. Five patients (one with a negative SLN, four with a positive SLN) had been elected pre-operatively to undergo ALND regardless of findings on SLN biopsy. ALND confirmed the SLN to be negative in one patient (false-negative rate: 0%) and three of the four patients with positive SLN(s) had additional positive nodes in the axilla. SLN biopsy accurately predicted axillary lymph node status in these five patients. These findings compare favourably with findings reported in the literature regarding SLN biopsy in female breast cancer patients. SLN biopsy accurately staged the axilla in male breast cancer patients and should be considered for axillary staging in male breast cancer patients with clinically negative axillae.     

Epstein-Barr virus expression in Hodgkin’s lymphoma in Kuwait

The epidemiology of Hodgkin's lymphoma (HL) shows wide geographic variation in histological subtypes and in its association with the Epstein-Barr virus (EBV). The proportion of EBV positive HL is low in industrialized countries, high in non-industrialized countries and intermediate in early-industrialized countries. Reports from the Persian Gulf and Middle East are very limited. The aim of this study was to determine the epidemiology of HL in Kuwait, an early-industrialized country in the Persian Gulf, and to delineate the extent of its association with EBV. We reviewed 134 cases of HL for histological classification and demographic data. 107 cases were examined for the presence of EBV using immunohistochemistry (IHC) for the latent membrane protein I (LMPI) and in-situ hybridization (ISH) for EBVencoded RNA (EBER). 70.4% of the patients were males and 29.6% were females. The male: female ratio was 2.4:1. The mean age was 30.6 years (range, 4-71 years). Mixed cellularity HL (MCHL) was the most common subtype (45.5%), followed by nodular sclerosis (37.3%), nodular lymphocyte predominant (6.7%), lymphocyte rich (3%) and lymphocyte depletion (3%). 4.5% of cases were unclassifiable. EBV expression was seen in 56%, was significantly higher in MCHL, in children, and in males. Our findings suggest that the frequency of EBV expression in HL in Kuwait is similar to other early-industrialized countries. Further research from other countries in the Persian Gulf and the Middle East should shed more light on the epidemiology of HL and its relation to EBV in this region.     

美国国家健康及营养普查人群巨细胞病毒与癌症发生的相关性

目的 研究巨细胞病毒（CMV）的存在与癌症的关系。方法 回顾性分析1988—1994年参加国家健康及营养普查（NHANES Ⅲ）人群（年龄≥17岁）感染巨细胞病毒与患癌症的关系。结果 在来自NHANES Ⅲ的14 718名美国居民（≥17岁）中,CMV存在于有癌症史的患者中,皮肤癌及结直肠癌患者中稍高。CMV的加权流行率,女性较男性高出10%甚至更多,尤其在女性乳腺癌、宫颈癌及子宫癌等相关癌症中,CMV存在率稍高。且该流行率随着年龄的增长逐渐增加（P<0.01）。未经校正的逻辑回归分析表明,CMV的存在与癌症发生、皮肤癌和乳腺癌有相关性（P<0.01）,但校正性别、年龄、教育背景、种族、贫困收入比率、身体质量指数及吸烟和饮酒状况等混杂因素后,该相关性不再显著。结论 巨细胞病毒的存在与癌症相关性不显著。     

Association between C1019T polymorphism in the connexin 37 gene and Helicobacter pylori infection in patients with gastric cancer

Objective: To investigate the association between the connexin 37 C1019T polymorphism and Helicobacterpylori infection in patients with gastric cancer. Methods: 388 patients with gastric cancer (GC), 204 with chronicsuperficial gastritis (CSG) were studied. H. pylori was detected by gastric mucosal biopsies biopsy dyeing method.Connexin 37 gene polymorphism 1019 site genotypes were determined by gene sequencing technology. Genotypesand alleles frequencies were compared. Results: (1) Connexin37 gene 1019 site distribution frequency (CC type,TC type, TT type) in the CSG group was 18.1%, 45.1% and 36.8%; in the stomach cancer group it was 35.1%,45.9% and 19.%, conforming to the Hardy-Weinberg euilibrium. (2) In comparison with CSG group, thefrequency of Connexin37 C allele was higher in the gastric cancer group (58.0% vs 40.7%, OR = 2.01, 95%CI =1.58-2.57, P < 0.01). The prevalence of gastric cancer risk was significantly increased in the carriers of C allele(CC+TC) than in TT homozygote (OR = 2.47, 5%CI = 1.68- 3.610. (3) Gastric cancer patients complicated withHp infection 211 cases, gastric cancer group of the male patients with HP positive patients with 187 cases, 40cases of female patients with negative patients, 24 cases were HP positive, negative in 137 cases, control groupmale patients, 28 cases were Hp positive, negative in 95 patients, female patients with Hp positive 6 cases, 75cases were negative. On hierarchical analysis, the male group OR value was 15.9 (95%CI to 9.22-27.3), and thefemale OR was 2.19 (95%CI 0.88-5.59), indicating a greater contribution in males (P <0.01). After eliminationof gender effects, positive HP and gastric cancer were closely related (OR 8.82, 95% CI: 5.45-14.3). (4) Thedistribution frequency of C allele in patients with Hp infection was much higher than that in Hp negative casesin the GC group (64.5% vs 47.0%, OR = 2.05, 95%CI = 1.54-2.74, P < 0.01). Compared with TT homozygotes,(CC+TC) genotype prevalence of gastric cancer risk increased significantly (OR = 2.96, 5%CI = 1.76-2.99 ).Conclusion: The T allele in the connexin37 gene might not only be associated with gastric cancer but also withH. pylori infection.     

Identification of Hepatic Cirrhosis by Duplex Doppler Ultrasound Value of the Hepatic Artery Resistive Index

Pulsed Doppler Ultrasound was used to analyze hepatic artery wave forms near the porta hepatis. The Resistive Index (RI) = [pcak systolic frequency shift (A) - minimum diastolic frequency shift (B)] / [peak systolic frequency shift (A)] has been calculated from this information. Two populations have been compared; 30 fit hospital staff members, 23 male, 7 female, age mean 37 years and range 19 to 73 years, and 33 cirrhotic potential liver transplant recipients, 16 male, 17 female, age mean 48 years and range 11 to 78 years. The RI was successfully obtained in 94% of the potential transplant patients. There is a significant difference between the RI of the controls (mean = 0.72, SE = 0.2, n = 27) and the cirrhotics (mean = 0.82, SE = 0.2, n = 31), P<0.0001. Using a cut off of greater than 0.77 this index has a sensitivity, specificity and overall accuracy of 68%, 70% and 69% respectively.     

Breast cancer, cytomegalovirus and Epstein�CBarr virus: a nested case�Ccontrol study

Background:

We investigated whether elevation in serum cytomegalovirus (CMV) or Epstein–Barr virus (EBV) immunoglobulin G (IgG) antibody levels precedes the development of breast cancer.

Methods:

A nested case–control study was carried out within the Janus Serum Bank cohort. Two serum samples, one taken at least 4 years before diagnosis (sample 2) and an earlier sample (sample 1) from 399 women with invasive breast cancer and from 399 controls, matched for date of blood samples and age were tested for CMV and EBV IgG antibodies. Odds ratios (ORs) with 95% confidence intervals (CIs) for CMV and EBV seroconversion between the samples and unit changes in IgG optical density (OD) examined as a continuous variable were calculated using conditional logistic regression.

Results:

Eleven cases and three controls seroconverted for CMV IgG between the first and second blood samples, with an adjusted OR for CMV IgG seroconversion of 4.0 (95% CI=1.1–14.4). The risk of breast cancer, adjusted for parity, increased per unit difference in CMV OD between samples (OR=1.7, 95% CI=1.1–2.5). In an analysis restricted to parous cases and age-matched parous controls, the OR for CMV seroconversion for IgG between the two samples, adjusted for parity and age at first birth, was 9.7 (95% CI=1.2–77.3). The EBV seroconversion or change in EBV OD was not associated with risk of breast cancer.

Conclusion:

Our hypothesis that elevation in serum CMV IgG antibody levels precedes the development of breast cancer in some women is supported by the results of this study. Changes in EBV IgG antibody are not associated with risk of breast cancer.     

Prospective observation: Clinical utility of plasma Epstein–Barr virus DNA load in EBV-associated gastric carcinoma patients

Epstein–Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.     

Association of the p73 Gene G4C14-to-A4T14 Polymorphism with Increased Gastric Cancer Risk in a Northwestern Chinese Population

OBJECTIVE To evaluate the p73 gene G4C14-to-A4T14 double nucleotide polymorphism with both increased gastric cancer(GC) risk and different histological subtypes of GC in a northwestern Chinese population. METHODS Genotyping of the polymorphism of the p73 gene was conducted with PCR-CTPP. RESULTS All 385 GC patients including 305 diffuse-type and 80 intestinal-type cases and 412 healthy controls were investigated.The frequencies of p73 AT/AT,AT/GC,and GC/GC genotypes were 28.1%,47.1%,and 24.8% in the controls,and were 22.0%,45.0%,and 33.0% in GC cases respectively;the GC/GC homozygote frequency was higher in GC cases,mainly in diffuse type compared to the controls with OR=1.71(1.16～2.51) and 1.87 (95%CI,1.24～2.81) respectively.The results showed that carriers of the p73 G4A GC/GC homozygote had a 1.71-time higher risk of GC,especially of the diffuse-type GC compared to the controls. The carriers of the AT/GC heterozygote also had a slightly increased risk of GC cancer,mainly on intestinal-type GC.This is the first report that the p73 G4A double-nucleotide polymorphism is associated with an increased risk of diffuse-type gastric cancer. CONCLUTION The p73 G4A GC/GC genotype is associated with an increased risk of gastric cancer,especially of the GC diffuse-type.     

Epstein-Barr virus-associated gastric carcinoma in Papua New Guinea

Using in situ hybridization assay, we examined Epstein-Barr virus (EBV) encoded RNA (EBER) expression in 66 cases of oral cancer, 40 esophageal cancer cases, 150 stomach cancer cases, and 46 colorectal cancer cases diagnosed in the Pathology Department of Port Moresby General Hospital, University of Papua New Guinea during the period between 1986-2002. There were no malignancies with positive EBER expression except for the following two male stomach cancer cases: a male case with a gastric carcinoma in pylorus whose age was unknown; and a male case aged 55 years without information on location of tumor. Both cases were histologically classified as non-solid poorly differentiated adenocarcinoma of the Japanese histological classification. The frequency of EBV-associated gastric carcinomas was 1.3% (2/150), and was the lowest ever reported in the world. We examined genotypes of two EBV strains detected from gastric carcinomas. Four different regions of EBV genome were examined by PCR-RFLP, coupled with Southern blot hybridization. The EBV genotype of the first case were type A, wild-type F at BamHI-F region, type D of BamHI-I region and the kept type of the XhoI cleavage site in LMP1. The second case had EBV whose genotypes were type A, wild-type F at BamHI-F region, and the kept type of the XhoI cleavage site in LMP1. The BamHI-I region of this case could not be analyzed.