Search

In the present study, in order to clarify the preventive mechanism of N‑acetyl‑L‑cysteine (NAC) on arsenite‑induced apoptosis in U937 cells, which lack functional p53, the cytotoxicity among U937 cells [monocytes and 12‑O‑tetradecanoylphorbol‑13‑acetate (TPA)‑treated macrophages] receiving NAC treatment at different times post arsenite treatment was examined. TPA‑treated macrophages were more resistant to arsenite‑induced apoptosis than monocytes, which may be associated with the induction of Bcl‑2 expression. Pretreatment with 20 mM NAC prior to arsenite exposure suppressed apoptosis up to 75% in the monocytes and 100% in the macrophages. However, 6‑h NAC pretreatment and subsequent washing out of NAC from the culture medium prior to arsenite treatment did not inhibit the arsenite‑induced apoptosis. Post‑treatment by NAC up to 1 h following arsenite exposure almost completely inhibited the cytotoxic effects of arsenite in U937 monocytes and macrophages. The results of the current study indicate that the preventive mechanism of NAC on arsenite‑induced apoptosis in U937 monocytes and macrophages mainly involves chelation of arsenite in culture medium.

Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship., (Published by Oxford University Press 2014.)

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., (© 2013 UICC.)

Background and Objective: About 9% of gastric carcinomas have Epstein-Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors., Methods: We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity., Results: During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4)., Conclusions: Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association.

Selenoneine is the major selenium compound in fish muscles, and fish appears to be an important source of selenium in the fish-eating population. Selenoneine has strong antioxidant activity and a detoxifying function against methylmercury (MeHg) toxicity. Dietary intake, bioaccumulation, and metabolism of selenoneine have not been characterized in humans. A nutritional survey was conducted in remote islands of the Kagoshima Prefecture in Japan. To evaluate the potential risks and benefits of fish consumption for health, we measured concentrations of selenoneine, total selenium, MeHg, inorganic mercury, and polyunsaturated fatty acid (LC-PUFA) in the blood of a fish-eating human population. The erythrocyte, leukocyte, and platelet residues following removal of serum (cellular fraction) contained 0.510 μg Se/g, 0.212 μg selenoneine Se/g, and 0.262 μg Se-containing proteins Se/g, whereas the serum contained 0.174 μg total Se/g. Selenoneine was highly concentrated in the cellular fraction in a manner that was dependent on subjects' frequency of fish consumption. Concentrations of selenoneine were closely correlated with concentrations of MeHg in the cellular fraction. Selenoneine is the major chemical form of selenium in the blood cells of this fish-eating human population and may be an important biomarker for selenium redox status.

Namie Town was heavily contaminated by the Fukushima Daiichi Nuclear Power Station accident. The thyroid equivalent dose for residents who lived in Namie was estimated using results of whole body counting examinations which were carried out by the Japan Atomic Energy Agency a few months after the nuclear accident. Photon peaks of (131)I and (134)Cs were previously measured by the authors using a NaI(Tl) scintillation spectrometer and that information was used to estimate the (131)I/(134)Cs activity ratio of total intake in the present study. The maximum values of (131)I/(134)Cs activity ratio corresponding to thyroid uptake factors of 0.3, 0.1 and 0.03 were evaluated to be 0.9, 2.6 and 8.7, respectively. The maximum value of the (131)I/(134)Cs activity ratio was used to obtain the most conservative thyroid equivalent dose estimation. The maximum internal exposure of the thyroid to (131)I on the basis of (134)Cs accumulated in the body measured by the whole body counter was estimated to be 18mSv. This value was much smaller than 50mSv that the International Atomic Energy Agency recommends as the dose at which exposed persons should take stable iodine tablets., (© 2013 Elsevier Ltd. All rights reserved.)

Aim: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses., Methods: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16(INK4a) expression in HPV-positive and HPV-negative cases was also made., Results: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16(INK4a) proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs., Conclusion: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

Aim: To clarify the reason for the low frequency of Epstein-Barr virus-associated gastric carcinoma (EBVaGC) in Peru, despite the high frequency reported in neighboring countries, the distribution of the distinctive EBV (type i/XhoI+) strain in EBVaGC and a healthy population was examined., Materials and Methods: EBV polymorphisms in BamHI W1/I1 and XhoI restriction site of the latent membrane protein 1 gene (LMP1) were examined among 11 EBVaGCs and 172 healthy controls from Peru, and these frequencies were compared with those in a previous study of Chile and Colombia (n=303)., Results: The frequency of the distinctive EBV strain in EBVaGCs (55%) was significantly higher than that in controls (7%). Furthermore, the frequency of this EBV type in Peruvian controls was significantly lower than that in controls from Chile and Colombia (27%, p<0.001)., Conclusion: The low frequency of the distinctive EBV strain among the Peruvian population might be a reason for the lower incidence of EBVaGC in Peru, as compared with neighboring countries.

The role of human papillomavirus (HPV) in the development of lung and esophageal cancer remains inconclusive, which is in contrast to the established role HPV plays in the development of uterine cervical cancer. One of the reasons for this is the difference among reported HPV infection rates in these cancers. An analysis of 485 lung and esophageal cancers (176 lung squamous cell carcinoma, 128 lung adenocarcinoma, 181 esophageal carcinoma) in eight institutions in Asia (Tokyo, Kochi, Kagoshima, and Okinawa, Japan; Seoul and Daegu, Korea; Changhua, Republic of China (Taiwan); Singapore, Singapore) was carried out in order to clarify infection rates with HPV. Samples were examined in one laboratory of the Department of Pathology, the University of Tokyo, Japan in order to avoid inter-laboratory variation using a combination of polymerase chain reaction and in situ hybridization (ISH). HPV was found in 6.3%, 7%, and 9.4% of patients with lung squamous cell carcinoma, lung adenocarcinoma, and esophageal cancer, respectively. Among the geographic areas surveyed, Kagoshima exhibited a significantly higher prevalence of HPV infection in cases of esophageal carcinoma (24.1%). There was no geographical difference in the infection rates of HPV in lung carcinomas. Subtype-specific ISH was also performed, which identified the high-risk HPV types 16/18 in the majority (75.7%) of the patients with lung and esophageal cancer positive for HPV., (Copyright © 2011 Wiley-Liss, Inc.)

Human papillomavirus (HPV) has been implicated in breast carcinogenesis. Consecutive and non-selected mastectomy specimens from Mexican patients harboring breast carcinomas were sampled in order to look for the presence of HPV DNA. HPV-16 was detected in 6 (10%) of 60 breast carcinomas. Two of these also had HPV genome in adjacent non-neoplastic mammary-tissues. Seven cases had HPV DNA only in non-neoplastic tissue specimens. HPV DNA was also detected in 4 (25%) of 10 tumor-bed specimens without residual neoplastic lesions that were obtained from patients who underwent neoadjuvant chemotherapy or neoadjuvant chemotherapy/radiotherapy. HPV-positive tumors tended to be smaller in size, than HPV-negative tumors (p=0.047). Histological distributions of HPV-positive and -negative cases showed no significant difference. Although all the HPV-16 DNA were found integrated, its low viral load rendered it difficult to incriminate this virus in breast carcinogenesis. However, the possibility that HPV infection occurred during carcinoma development cannot be ruled out., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The Karunagapally cohort in Kerala, India was established in the 1990s. The present study examined oral cancer risk among 66,277 men aged 30-84 years in the cohort, using Poisson regression analysis of grouped data, stratified on attained age, calendar time, education, and family income. By the end of 2005, 160 oral cancer cases were identified by the Karunagapally Cancer Registry. Tobacco chewing increased oral cancer risk (P < 0.001). Particularly increased was the risk of cancers of the gum and mouth (relative risk [RR] = 4.7; 95% confidence interval [CI] = 2.8-7.9), which increased with higher daily frequencies (P < 0.001) and longer duration (P < 0.001) of tobacco chewing. Alcohol drinking was not significantly related to oral cancer risk regardless of tobacco chewing. Bidi smoking significantly increased oral cancer risk (RR = 2.6; 95%CI = 1.4-4.9) only among men without tobacco chewing habits. The risk increased with higher daily consumption (P < 0.001), longer duration (P = 0.001), and younger age at start of bidi smoking (P = 0.007). In location-specific analysis, bidi smoking was significantly associated with cancer of the gum and mouth (RR = 3.6; 95%CI = 1.1-12.1), and its risk significantly increased with larger daily consumption of bidis (P = 0.013) and younger age at the start of smoking (P = 0.044). Tongue cancer risk was significantly increased among men who smoked bidis for 30 years or longer, and men started bidi smoking at 18 years old or younger. The present study is the first cohort study showing that tobacco chewing increases cancers of the gum and mouth among men keeping chewing tobacco in the cheek, and that bidi smoking strongly increased oral cancer risk among men without a tobacco chewing habit., (© 2010 Japanese Cancer Association.)

Background: The Lao PDR is a landlocked country with 5,920,000 inhabitants for which very few epidemiological studies on cancer have been performed. The aim of the present study was to examine cancer mortality in 2007-2008., Methods: A descriptive cancer epidemiology protocol was designed with a data collection form and guideline for both demographics and list of all deaths from all 757 local Health Centers of 17 provinces/ cities. Five indicators, name, age, sex, date of death and the cause of death (ICD-10), were collected for each case. The age-specific cancer mortality rate and ASRs per 100,000 were estimated., Results: There were 448 cancer cases reported from Health Centers within 7 of 17 provinces/cities. Number of person-years was 654,459 for the two-year period. Cancer mortality rates of all sites (ASR) were 116.7 and 97.2 per 100,000 in males and females, respectively. The five most common cancers causing mortality per 100,000 were liver (52.2), followed by colorectal (19.0), lung (17.3), stomach (6.9), and leukemia-lymphoma (7.2) in males and liver (28.4); followed by colorectal (19.0), lung (14.0), cervical uteri (9.2) and stomach (7.1) in females., Conclusions: Liver and colorectal cancers were the first and second most common, respectively, in both males and female.

Unlabelled: The aim of the present study was to elucidate the etiological roles of Epstein-Barr virus (EBV) in the development of EBV-associated GC (EBV-GC), EBV-GCs and non EBV-GCs were compared with regard to the expression of thymidine phosphorylase (TP), which is known to have angiogenic activity in various tumor tissues., Patients and Methods: TP expression was examined by immunohistochemistry assay among 156 gastric carcinoma cases (21 EBV-GC cases and 135 non EBV-GC cases)., Results: The frequency of tumors with TP expression was nearly twice as high in EBV-GCs (71%) than in non EBV-GCs (37%) (p=0.005). However, such an association was only observed in Lauren's diffuse-type tumors., Conclusion: Our finding suggests that the mechanism involved in TP expression of gastric carcinoma appears to be different in intestinal- and diffuse-type tumors.

Kagoshima bay has a highly active volcano in its center. In the filtered seawater and suspended matter collected from 200-m deep fumaroles at the bottom of the inner bay, the geometric mean concentrations of total mercury were 7.6 and 65.0 ng/L, respectively. The surface seawater collected at the inner bay had a higher concentration of mercury when compared to that in the bay entrance (average: 1.0 vs. 0.5 ng/L). In July, however, no such difference was observed. The fumaroles seem to contribute to relatively high concentrations of mercury in the inner bay except in summer, when thermal cline is formed.

A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.

Lifestyle factors related to breast cancer risk were examined in a case-control study nested in a cohort in Karunagappally, Kerala, South India. We sought interviews with all the residents in Karunagappally with the population of 385,103 (191,149 males and 193,954 females) in the 1991 census and established a cohort of 359,619 (93% of the population in 1991) in 1990. For analysis 264 breast cancer cases with age > or = 20 years were selected from 438 breast cancer cases reported during the period 1990-2004 and for each case 3 non-cancer controls were randomly selected matched for age, religion and place of residence through the Cancer Registry, Karunagappally. Conditional logistic regression was used for the analysis. In the present study, in addition to a low number of pregnancies (P <0.001 and P for trend <0.001), more frequent intake of roots and tubers except tapioca (cassava) (OR for > or = 5 times =1.56, 95% CI=1.09, 3.09, P for trend <0.05), milk drinking (OR=1.78, 95% CI=1.17-2.69, P<0.01) and consumption of chicken meat (OR=1.84, 95% CI=1.09-3.09, P<0.05) were found to increase breast cancer risk. The present study further showed that consumption of tapioca which is a commonly used food item in South India, particularly in Kerala, reduced breast cancer risk (OR=0.55, 95% CI=0.37-0.83, P<0.01). Risk analysis was attempted among pre- and post-menopausal women separately and similar odds ratio were obtained. Consumption of tapioca (cassava) decreased risk of developing breast cancer among premenopausal women (P<0.001 and OR=0.35, 95% CI=0.18, 0.65) and a low number of pregnancies (P<0.01), consumption of roots & tubers (P<0.05), usage of chicken meat (P=0.05) increased the risk of breast cancer among post-menopausal women. Further studies seem warranted to confirm the possible protective effect of tapioca consumption. There is an increasing need of breast cancer prevention programs responsive to the cultural practices of the people and the study results should provide leads to cancer control programs especially in rural areas.

Several independent studies have presented evidence for the involvement of human papillomaviruses (HPV) in the aetiology of human breast cancer, while others have reported the opposite findings. Here, we have analysed by a high sensitive multiplex PCR-based method the prevalence of alpha mucosal and beta cutaneous HPV DNA in 90 ductal lavages, colostrum and milk. Ten of the 70 DLs analyzed (14%) contained a single or multiple beta HPV types, while DNA from mucosal high-risk HPV types was detected in only one sample (1/70). A strong reduction of HPV positivity in DL fluids was observed in 45 specimens collected after removal of the superficial layers of the nipple epidermis. All DLs were negative for the mucosal low-risk HPV types 6 and 11. Finally, HPV positivity was low in colostrum and milk. Our data show that DNA of alpha mucosa and beta cutaneous HPV types are rarely present in the breast fluids and suggest that a direct role of HPV in breast carcinogenesis is unlikely.

The association of lung cancer incidence with bidi smoking was examined using a cohort study data in Karunagappally, Kerala, India. We sought interview of all the residents in Karunagappally with the population of 385,103 in 1991 census, and established a cohort of 359,619 (93% of the population in 1991) in the 1990s. There were 65,829 men aged 30-84 at interview after excluding those diagnosed as cancer or died of any cause before 1997. Among them, 212 newly diagnosed lung cancer cases were ascertained during the 8-year period between 1997 and 2004 through Karunagappally Cancer Registry. The relative risk (RR) of lung cancer was obtained from Poisson regression analysis of grouped data. Lung cancer incidence was relatively high among Moslem people and those with lower educational history. When taking into account attained age, religion and education, the RR between current bidi smokers and those who had never smoked bidis was 3.9 (95%CI = 2.6-6.0, p < 0.001). The lung cancer risk did not return to the level of non-smokers within 10 years after cessation. In further analyses using only those never smoked cigarettes to examine the effect of bidi smoking alone on lung cancer risk, current smokers of bidis had the RR of 4.6 (95%CI = 2.5-8.5, p < 0.001). Lung cancer incidence increased with larger amounts of bidi smoked a day (p < 0.001), with longer durations of smoking bidis (p < 0.001), and with younger ages starting smoking bidis (p < 0.001). Immediate measures should be taken to stop bidi smoking, which is common in south Asia., (Copyright 2008 Wiley-Liss, Inc.)

In this paper, the roles of Epstein-Barr virus (EBV) in gastric carcinogenesis are discussed, reviewing mainly epidemiological and clinicopathological studies. About 10% of gastric carcinomas harbor clonal EBV. LMP1, an important EBV oncoprotein, is only rarely expressed in EBV-associated gastric carcinoma (EBV-GC) while EBV-encoded small RNA is expressed in almost every EBV-GC cell, suggesting its importance for developing and maintaining this carcinoma. In addition, the hypermethylation-driven suppressor gene downregulation, frequently observed in EBV-GC, appears to give a selective advantage for carcinoma cells. EBV reactivation is suspected to precede EBV-GC development since antibodies against EBV-related antigens, including EBV capsid antigen (VCA), are elevated in prediagnostic sera. Interestingly, the average anti-VCA immunoglobulin G antibody titer in EBV-GC patients was significantly higher among men than among women, whereas EBV-negative GC cases did not show such a sex difference. A higher frequency of human leucocyte antigen-DR11 in EBV-GCs suggests that major histocompatibility complex-restricted EBV nuclear antigen 1 epitope recognition may enhance EBV reactivation. EBV infection of gastric cells by lymphocytes with reactivated EBV is suspected to be the first step of EBV-GC development. Male predominance of EBV-GC suggests the involvement of lifestyles and occupational factors common among men. The predominance of EBV with XhoI+ and BamHI type i polymorphisms in EBV-GC in Latin America suggests a possibility of some EBV oncogene expressions being affected by EBV polymorphism. The lack of such predominance in Asian countries, however, indicates an interaction between EBV polymorphism and the host response. In conclusion, further studies are necessary to examine the interaction between EBV infection, its polymorphisms, environmental factors, and genetic backgrounds.

Aim: To examine the role of E-cadherin and beta-catenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas (EBV-GCs)., Methods: We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients' prognosis and the expressions of these proteins., Results: Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta-catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 95% confidence interval (CI), 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequently in EBV-GCs than non-EBV-GCs (odds ratio = 2.23; 95% CI, 0.97-5.09), and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs (P = 0.024). Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis (P < 0.001). Among EBV-GCs, the depth of invasion (P = 0.005), lymph node metastasis (P = 0.004) and an intestinal type by Lauren classification (hazard ratio = 9.47; 95% CI, 2.67-33.6) were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC (hazard ratio = 0.32; 95% CI, 0.11-0.93)., Conclusion: We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV-GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

The presence of mercury in the environment is widespread and persistent, but the extent of exposure of Pakistanis to mercury is virtually unknown. We collected toenail and scalp hair samples from 158 subjects (83 males and 75 females) residing in Lahore and its suburbs. We also conducted a questionnaire survey and personal interviews to obtain information on demographic factors, lifestyles, and socioeconomic factors, among others. Mercury concentration in hair samples was measured by cold vapor atomic absorption spectrometry (CVAAS). In addition, the concentration of selenium in the toenail and hair samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The mean hair mercury concentration was 0.45 ppm (95% CI = 0.34-0.60) and did not show correlation with fish consumption, age, area of origin, or present residence. Mercury concentration was higher (p = 0.021) in females than in males, and was also higher in subjects with 11 or more years of education (p for trend = 0.013). There were 13 subjects with mercury concentration higher than 10 ppm. Most of them were young females and a few were middle-aged males. When the analysis was confined to subjects with mercury concentrations lower than 0.6 ppm, the amount of fish consumed showed correlation with hair mercury concentration with a marginal statistical significance (p = 0.065). The geometric means of selenium in hair and toenails were 0.87 and 1.01 ppm, respectively. Mercury and selenium concentrations in hair showed no correlation (correlation coefficient = 0.057, p = 0.478). This study shows that mercury exposure levels among residents in Lahore and its suburban areas are relatively low, except among outliers, wherein mercury exposure might be brought about by the use of mercury-containing soaps.

The inactivation of tumour suppressor genes by aberrant methylation of promoter regions has been described as a frequent event in neoplasia development, including lung cancer. The p16 gene is a tumour suppressor gene involved in the regulation of cell cycle progression that has been reported to be inactivated by promoter methylation in lung carcinomas at variable frequencies around the world in a smoking habit dependent manner. The purpose of this study was to investigate the methylation status of the promoter region of the p16 gene in 74 non-small cell lung carcinomas from Chile. The frequency of p16 gene inactivation by promoter methylation was determined as 79.7% (59/74). When we considered histological type, we observed that p16 promoter methylation was significantly higher in squamous cell carcinomas (30/33, 91%) compared with adenocarcinomas (21/30, 70%) (p=0.029). In addition, no association between p16 promoter methylation and gender, age or smoking habit was found (p=0.202, 0.202 and 0.147 respectively). Our results suggest that p16 promoter hypermethylation is a very frequent event in non-small cell lung carcinomas from Chile and could be smoking habit-independent.

Aim: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively., Methods: We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5+/GP6+ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16(INK4A) protein immunostaining of all the specimens was conducted., Results: HPV was detected in 21 ESCC specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 (without statistical significance), but a significantly lower prevalence of HPV-18 than in Colombian cases (P = 0.011) even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country., Conclusion: HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

Epstein-Barr virus (EBV)-encoded small RNA can be detected in about 1-17 % of gastric carcinomas. To elucidate lifestyles and other factors related to such an EBV-associated gastric carcinoma (EBV-GC), we conducted a case-control study in Cali, Colombia. The study subjects were 368 patients with gastric carcinoma newly diagnosed during the period between September 2000 and June 2003, including 42 EBV-GC cases. We obtained information on lifestyles, dietary habits, and occupational exposure by a questionnaire. The frequency of EBV-GC was related to birth order of patients (P for trend =0.025). More precisely, EBV-GC was much less frequent among the patients who were the eldest child in a family (P=0.007). Those findings were contrary to what was reported by the study conducted in Japan, where EBV-GC was more frequently observed among eldest brothers/sisters. A possible explanation for the apparently conflicting results is that EBV-GC risk is related to the age at first EBV infection but its relationship is not monotonic. In addition to the relationship with birth order, the present study showed that high salt intake and metal dust exposure may be related to EBV-GC as reported by the Japanese study although these associations observed in the present study were not statistically significant. No significant association was observed in other factors, including dietary habits. Further studies seem warranted to elucidate the difference between Japan and Colombia with respect to the environmental factors related to EBV-GC cases.

Aim: To examine histology- and tumor-location specific risk factors of gastric cancer (GC)., Methods: This was a case-control study. The study subjects were 216 GC patients newly diagnosed during the period 2000-2002 and 431 controls selected from non-cancer patients matching in age, gender, and hospital. We obtained information on lifestyles, dietary habits, and others by a questionnaire., Results: The subjects who were not eldest among his/her siblings were at a slightly elevated GC risk (OR 1.3; 95% CI 0.8-2.0). Salting meals before tasting was related to an increased GC risk (OR 3.5; 95% CI 1.6- 7.3). Frequent consumptions of fruits (OR 0.3; 95% CI 0.1-1.0) and vegetables (OR 0.3; 95% CI 0.1-1.0) were related to decreased GC risks. On the other hand, frying foods (OR 1.9; 95% CI 1.0-3.6) and cooking with coal (OR 1.8; 95% CI 1.3-2.6) were related to increased GC risks. Neither Laurenos histological classification (intestinal and diffuse types) nor tumor location significantly affected those associations except birth order. The subjects who were not eldest among his/her siblings had an increased risk of GCs in the distal and middle thirds, and their ORs were 1.7 (95% CI 1.0-2.8) and 1.9 (95% CI 0.8-4.3), respectively. The corresponding OR in the upper third stomach was 0.3 (95% CI 0.1-0.9). The differences of those three ORs were statistically significant (P = 0.010)., Conclusion: The present study shows that birth order, salt intake, consumption of fruits and vegetables, the type of cooking, and cigarette smoking are related to GC risk. In histology and tumor-location specific analyses, non-eldest person among their siblings is related to an increased GC risk in the distal and middle thirds of the stomach, and is related to a decreased GC risk in the cardia.

The Chernobyl accident, which occurred April 26, 1986, resulted in a large release of radionuclides, which were deposited over a very wide area, particularly in Europe. Although an increased risk of thyroid cancer in exposed children has been clearly demonstrated in the most contaminated regions, the impact of the accident on the risk of other cancers as well as elsewhere in Europe is less clear. The objective of the present study was to evaluate the human cancer burden in Europe as a whole from radioactive fallout from the accident. Average country- and region-specific whole-body and thyroid doses from Chernobyl were estimated using new dosimetric models and radiological data. Numbers of cancer cases and deaths possibly attributable to radiation from Chernobyl were estimated, applying state-of-the-art risk models derived from studies of other irradiated populations. Simultaneously, trends in cancer incidence and mortality were examined over time and by dose level. The risk projections suggest that by now Chernobyl may have caused about 1,000 cases of thyroid cancer and 4,000 cases of other cancers in Europe, representing about 0.01% of all incident cancers since the accident. Models predict that by 2065 about 16,000 (95% UI 3,400-72,000) cases of thyroid cancer and 25,000 (95% UI 11,000-59,000) cases of other cancers may be expected due to radiation from the accident, whereas several hundred million cancer cases are expected from other causes. Although these estimates are subject to considerable uncertainty, they provide an indication of the order of magnitude of the possible impact of the Chernobyl accident. It is unlikely that the cancer burden from the largest radiological accident to date could be detected by monitoring national cancer statistics. Indeed, results of analyses of time trends in cancer incidence and mortality in Europe do not, at present, indicate any increase in cancer rates -- other than of thyroid cancer in the most contaminated regions -- that can be clearly attributed to radiation from the Chernobyl accident.

Residential power-frequency magnetic fields (MFs) were labeled as a possible human carcinogen by the International Agency for Research on Cancer panel. In response to great public concern, the World Health Organization urged that further epidemiologic studies be conducted in high-exposure areas such as Japan. We conducted a population-based case-control study, which covered areas inhabited by 54% of Japanese children. We analyzed 312 case children (0-15 years old) newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myelocytic leukemia (AML) in 1999-2001 (2.3 years) and 603 controls matched for gender, age and residential area. Weekly mean MF level was determined for the child's bedroom. MF measurements in each set of a case and controls were carried out as closely in time as possible to control for seasonal variation. We evaluated the association using conditional logistic regression models. The odds ratios for children whose bedrooms had MF levels of 0.4 microT or higher compared with the reference category (MF levels below 0.1 microT) was 2.6 (95% CI=0.76-8.6) for AML+ALL and 4.7 (1.15-19.0) for ALL only. Controlling for some possible confounding factors did not alter the results appreciably. Even an analysis in which selection bias was maximized did not fully explain the association. Most of the leukemia cases in the highest exposure category had MF levels far above 0.4 microT. Our results provided additional evidence that high MF exposure was associated with a higher risk of childhood leukemia, particularly of ALL., (Copyright (c) 2006 Wiley-Liss, Inc.)

Epstein-Barr virus (EBV) has been linked to gastric carcinoma (GC) with worldwide geographical variations attributable to types and variants of EBV. Here, we compare EBV strains between EBVaGC and healthy donors in Latin America, a high frequency area for EBVaGC. Tumor samples from 73 EBVaGC cases and throat washings from 329 healthy adults were examined for types 1 and 2 EBV and polymorphism at BamHI-F and BamHI-W1/I1 boundary regions and XhoI restriction site in LMP1 gene. Type 1 and prototype F of BamHI- F polymorphism accounted 59 (81%) and 69 (95%) of EBVaGC cases and 257 (78%) and 267 (81%) of healthy donors, respectively. Types I and "i" of BamHI W1/I1 polymorphism accounted 2 (3%) and 62 (85%) of EBVaGC and 85 (26%) and 170 (52%) of healthy donors, respectively (p<0.001). XhoI+ and - polymorphism accounted 60 (82%) and 4 (5%) of EBVaGC and 142 (43%) and 92 (28%) of healthy donors, respectively (p<0.001). Cosegregation analysis demonstrated that most of the 62 type "i" EBVaGC cases harbor XhoI+ strain (81%). However, among 143 type "i" healthy adults, both XhoI polymorphism were present in relatively similar frequencies (XhoI+ 58% and XhoI- 42%) (OR 9.0; 95% CI 1.2-69). Our findings are against to the proposed hypothesis that EBV strains are geographically but not disease-restricted. We conclude that most of the EBVaGC cases harbor a distinctive EBV strain (type "i"/XhoI +), but in healthy donors, this strain was as common as other strains. This finding is contrary to the proposed hypothesis that EBV strains are geographically but not disease-restricted and identified a healthy population group that share the same strain that predominate in EBVaGC cases.

In order to evaluate the current arsenic exposure status and its determinants in Japan, we collected toenail samples from 212 subjects residing in a town with a population of 6,900 in Amami-Oshima Island in August 1999. We measured arsenic concentrations of the toenails using inductively coupled plasma mass spectrometry. In addition, we examined the association of arsenic levels with lifestyles and dietary habits, including the consumption of fish, seaweed, and rice. The mean toenail arsenic level was 0.41 ppm (95% confidence interval, 0.36-0.47), which was about 3-fold higher than those observed in other populations of mainland Kagoshima. Arsenic levels were elevated among current smokers (mean = 0.65; 95% confidence interval, 0.32-1.29) when compared with non-smokers (mean = 0.40; 95% confidence interval, 0.34-0.46), and among the residents consuming 4 bowls or more, of rice every day (mean = 1.97; 95% confidence interval, 0.25-15.75) when compared to residents consuming 3 bowls or less (mean = 0.39; 95% confidence interval, 0.34-0.45). Sex, age, alcohol intake, fish consumption, or seaweed consumption was not associated with toenail arsenic concentration. Further studies seem warranted to examine the cause of relatively high arsenic levels in our study area.

Aim: To investigate features of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) among a Mexican population., Methods: Cases of primary gastric adenocarcinoma were retrieved from the files of the Departments of Pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City. The anatomic site of the gastric neoplasia was identified, and carcinomas were histologically classified as intestinal and diffuse types and subclassified as proposed by the Japanese Research Society for Gastric Cancer. EBV-encoded small non-polyadenylated RNA-1 (EBER-1) in situ hybridization was conducted to determine the presence of EBV in neoplastic cells., Results: We studied 330 consecutive, non-selected, primary gastric carcinomas. Among these, there were 173 male and 157 female patients (male/female ratio 1.1/1). EBER-1 was detected in 24 (7.3%) cases (male/female ratio: 1.2/1). The mean age for the entire group was 58.1 years (range: 20-88 years), whereas the mean age for patients harboring EBER-1-positive gastric carcinomas was 65.3 years (range: 50-84 years). Age and histological type showed statistically significant differences, when EBER-1-positive and -negative gastric carcinomas were compared. EBER-1 was detected in hyperplastic- and dysplastic-gastric mucosa surrounding two EBER-1-negative carcinomas, respectively., Conclusion: Among Latin-American countries, Mexico has the lowest frequency of EBVaGC. Indeed, the Mexican population >50 years of age was selectively affected. Ethnic variations are responsible for the epidemiologic behavior of EBVaGC among the worldwide population.

Background: Mortality caused by cardial gastric cancer in Chile, is increasing. Previously we demonstrated an association between Epstein Barr virus and this specific location of gastric cancer., Aim: To perform a clinical and molecular characterization of cardial gastric cancer associated to Epstein Barr virus., Material and Methods: Epstein Barr virus was identified in 93 cardial gastric tumors, by in situ hybridization. Clinical and pathological features, survival and expression of p53 and c-erbB2 were compared between tumors with or without the presence of the virus., Results: Twenty two (23.6%) tumors expressed Epstein Barr virus. No difference in sex or age of patients with tumors positive or negative for the virus was observed. Epstein Barr positive tumors had a tendency to have a higher frequency of Bormann III endoscopic appearance and a lower frequency of p53 accumulation (p=0.06). Five years survival was 67% and 42% of tumors positive and negative for the presence of the virus, respectively (p=0.57)., Conclusions: Our results, although not significant, show a tendency towards unique characteristics of cardial gastric tumors associated to Epstein Barr.

We examined the prognosis of 64 EBV-associated gastric carcinoma (EBV-GC) cases and 128 EBV-negative gastric carcinoma cases. EBV-GCs were identified by detecting EBV-encoded small RNA (EBER) using in situ hybridization assay of paraffin-embedded tissue. For each EBV-GC case, 2 EBER-negative cases (EBV-negative cases) were selected, matching the EBV-GC case with respect to age, sex, tumor location, and depth of invasion. The average follow-up period was 70.9 months (SD=61.1) in EBV-GCs and 63.8 months (SD=59.7) in EBV-negative cases. Tumor-advanced stage determined by TNM classification of UICC, tumor location, and p53 over-expression were statistically significant prognostic factors. On the other hand, EBER expression was not related to the survival of patients. However, further analysis specific for intestinal and diffuse types of Lauren classification revealed that the association of EBER expression with prognosis was different in the two histological types. EBER expression was related to poor prognosis in intestinal-type carcinoma [hazard ratio (HR) =2.5, 95% confidence intervals (CI) =1.3-4.8] after adjusting for stage, p53 over-expression, and tumor location, whereas the diffuse-type EBV-GC had better prognosis (HR=0.4, 95% CI=0.2-0.9) even when lymphoepithelioma-like carcinomas were excluded. To examine the interactive prognostic effects between EBER expression and p53 over-expression, the study subjects were divided into 4 groups on the basis of EBER expression and p53 over-expression. In intestinal-type tumors, the cases having both EBER expression and p53 over-expression showed the poorest prognosis (HR=10.0, 95% CI=3.3-30.4), and the cases with either EBER expression or p53 over-expression had an intermediate prognosis. In diffuse-type tumor, only EBER was an important prognostic factor. These results give additional evidence implicating EBV in the natural history of EBV-GCs.