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Model-based patterns in stomach cancer mortality worldwide
Abstract
The decrease in stomach cancer mortality was not because of specific interventions, and is likely that different countries follow a similar model of variation. Here, we aimed to identify model-based patterns in the time trends of stomach cancer mortality worldwide. Stomach cancer mortality rates were retrieved for 62 countries from the WHO mortality database. Sex-specific mixed models were used to describe time trends in age-standardized rates between 1980 and 2010 (age group 35-74 years; World standard population). Three patterns, similar for men and women, were identified through model-based clustering. Pattern 1 presented the highest mortality rates in 1980 (median: men, 81.5/100 000; women, 34.4/100 000) and pattern 3 the lowest ones (median: men, 24.4/100 000; women, 12.4/100 000). The decrease in mortality rates was greater in 1980-1995 than during 1996-2010. Assuming that the patterns characterized by the highest rates precede temporally those with lower mortality, the overlap of model predictions supports a 20-year lag between adjacent patterns. We propose a model for the variation in stomach cancer mortality with three stages that develop sequentially through a period of ∼70 years. The countries with the lowest mortality had the highest proportional decrease in mortality rates.
... Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide, despite its incidence and mortality have been appreciably declining for several decades [1][2][3]. The fall in gastric cancer is mainly due to the decline in the prevalence of Helicobacter pylori (H. ...
... pylori) infection and tobacco smoking, and to the improvements in food preservation and diet [4]. However, the patterns in gastric cancer trends vary substantially across geographical regions [3,5], reflecting a heterogeneous distribution of the factors associated with gastric cancer incidence, survival and mortality, with time, over birth cohorts and across countries (Fig. 1). ...
... The burden of gastric cancer remains very high in several countries from Asia, Latin America and Central and Eastern Europe, whereas in North America and in most Western European countries it is no longer a common cancer [1,3,6]. Incidence rates showed differences according to tumour topography [7,8], with upward trends in cardia incidence [9,10]. ...
... A continued decline in gastric cancer incidence and mortality has been observed worldwide for several decades, though the trends differ between[1][2][3]and within countries[4][5][6][7][8]. The decrease in gastric cancer rates was primarily attributed to a set of factors related to the improvement of the populations' living conditions, including the increase in fruits and vegetables consumption and the decrease in salt intake[9]. ...
... It is estimated that H. pylori infection affects more than half of the adult population worldwide[13]and is responsible for 75 % of all gastric cancer cases[14]. The systematic assessment of large population-based surveys addressing the prevalence of infection may provide robust evidence for understanding the trends in the exposure to this major risk factor across settings with distinct patterns of variation in gastric cancer mortality[2]. We aimed to describe the prevalence of H. pylori infection in different countries and periods, through systematic review of studies with national coverage. ...
... The guidelines for management of H. pylori infection that have been adopted since the 1990s, targeting subjects with specific clinical conditions or broader segments of the population[55][56][57], may have also contributed to the observed declines[58]. In the Republic of Korea, which is among the countries with highest gastric cancer incidence and mortality rates[1,2], there was a substantial decline in the prevalence of infection from 1998 to 2005, reaching figures as low as those observed in settings with already low gastric cancer risk. Declines to similarly low prevalences were also observed in the Czech Republic during the last decade. ...
The systematic assessment of large population-based surveys addressing the prevalence of Helicobacter pylori infection may provide robust evidence for understanding the trends in the exposure to this major risk factor across settings with distinct patterns of gastric cancer variation. Our aim was to describe the prevalence of H. pylori infection in different countries and periods, through systematic review of the literature. We searched PubMed from inception up to September 2013 to identify original studies reporting on the prevalence of H. pylori, and only those evaluating samples with national coverage were included. We identified 37 eligible studies including data for 22 countries. The prevalences were higher in Central/South America and Asia, and at least two-fold higher in countries with high gastric cancer incidence. In most countries presenting data for different time periods, the prevalences were usually lower in the most recent surveys. However, there was little variation in settings where prevalences were already low. Among countries with high prevalence of H. pylori infection there is an ample scope for reducing its burden in the next decades, whereas further declines in settings with already low prevalences will require more intensive efforts.
... La France fait partie des pays, avec ceux de l'Europe de l'Ouest, l'Amérique du Nord et l'Océanie, où la mortalité du cancer gastrique est la plus faible au monde (Peleteiro et al., 2014). En effet, le nombre de décès estimé liés au cancer gastrique en 2018 en France est d'environ 4 000 cas, dont une majorité également (65 %) chez l'homme. ...
... En effet, le nombre de décès estimé liés au cancer gastrique en 2018 en France est d'environ 4 000 cas, dont une majorité également (65 %) chez l'homme. Ceci peut s'expliquer en partie par le fait que les taux de mortalité du cancer gastrique sont inversement corrélés au revenu national brut par habitant et donc au statut socioéconomique à l'échelle du pays (Lagergren et al., 2016;Peleteiro et al., 2014). Néanmoins, malgré les quelques progrès thérapeutiques touchant le cancer gastrique, son pronostic reste très sombre (Ajani et al., 2017;Allemani et al., 2018;Jim et al., 2017;Van Cutsem et al., 2016). ...
Le cancer gastrique avancé ou métastatique (CGA) est une maladie à pronostic très sombre, avec une survie médiane < 12 mois. L’irinotécan dans le CGA est une drogue anti-tumorale active avec un profil particulier de toxicité, surtout de type diarrhée chimio-induite retardée. Le paysage thérapeutique du CGA est vaste, sans traitement standard claire. Dans ce contexte, de nombreux essais randomisés ont comparé différentes associations de traitements entre elles, dont les chimiothérapies à base d’irinotécan. Une méta-analyse sur données individuelles (MADI) permet une analyse groupée de tous ces essais randomisés, en utilisant les données individuelles des patients disponibles pour déterminer l’efficacité relative des traitements. Le groupe GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) est un groupe international qui réalise des méta-analyses basées sur les données individuelles des patients atteints de CGA inclus dans les essais randomisés. Les comparaisons par paire généralisées (ou GPC pour Generalized Pairwise Comparisons en anglais) est une nouvelle approche statistique comparant les résultats multiples de chaque paire possible de patients. La méthode de GPC permet ainsi d’estimer la balance bénéfice-risque d’un traitement, en une métrique absolue probabiliste. L’objectif de cette thèse était double : clinique et méthodologique. Ainsi, notre travail a consisté à : 1. Décrire un nouveau biomarqueur candidat (la β-glucuronidase) prédictif de la sévérité de la toxicité gastro-intestinale de l’irinotécan (Premier objectif clinique).2. Evaluer l’impact de la durée de suivi qui peut varier entre les différents essais inclus dans une MADI sur la méthode de GPC (Premier objectif méthodologique). 3.Mettre à jour et réaliser la MADI de l’efficacité et de la toxicité de l’irinotécan, incluant les essais évaluant les chimiothérapies à base d’irinotécan grâce au groupe GASTRIC (Second objectif clinique). La MADI-GASTRIC a inclus 10 essais (n=2531 patients), et a utilisé différents critères de jugement (survie globale, survie sans progression et toxicité de type diarrhée chimio-induite sévère). 4.Appliquer la GPC à la MADI-GASTRIC, en calculant le Δ (irinotécan) global (Second objectif méthodologique).
... Gastric cancer (GC) is an aggressive malignancy with a globally increasing incidence, especially in eastern Asian countries [1,2]. Despite the advances in diagnostic and therapeutic strategies, the clinical outcomes of GC patients have not improved because of late diagnosis, tumor relapse, and drug resistance [3]. ...
... A total of 1 × 10 7 cells in 80 μl of PBS were subcutaneously transplanted into 6-week-old BALB/c female nude mice. Tumor volumes were measured every 3 days and calculated based on the equation: V = (length × width [2])/2. Five mice were used for each group. ...
Accumulating evidences indicate that 3ʹUTR of the coding gene can act as crucial regulators in gastric cancer (GC). However, the detailed mechanisms and responsive targets are not well established. Here, we found that acvr1b gene 3ʹUTR (acv3UTR) was elevated in GC tissue, the expression of which was significantly correlated with advanced pTNM-stage and poor outcome in clinical patients. Forced expression of acv3UTR promoted GC cells growth in vitro and in vivo. Mechanistically, our results suggested that acv3UTR functioned as an oncogenic competing endogenous RNA via sponging miR-590-5p and enhancing YAP1 level. Tumor suppressor miR-590-5p was a molecular module in acv3UTR regulatory axis, the forced expression of which led to impairing of oncogenic potential of acv3UTR. The positive correlation of acv3UTR and YAP1 expression, and the negative correlation of acv3UTR and miR-590-5p expression, were verified in GC patients. Moreover, CFIm25 was identified as a key regulator contributing to acv3UTR aberrant expression in GC binding to UGUA-264 motif. Overall, our finding defines a mechanism for understanding the potential role of acv3UTR transcription in GC tumorigenesis, and indicates a correlation between 3ʹUTR trans-regulatory effect and GC development.
... Thus, Hooi et al. [13] reported a prevalence of 63.4%, while the prevalence found by Zamani et al. [28] was 59.3%. Several studies performed on Alaska Native people highlighted that gastric cancer remains the third most frequent cause of cancerrelated death in this population [29][30][31], three times higher than among US whites [32]. Moreover, in this area, 75% of the people were found to have positive H. pylori IgG antibodies, considerably increasing their risk of developing gastric cancer [33,34] based on the close relationship between this infection and gastric carcinogenesis. ...
... Thus, Hooi et al. [13] reported a prevalence of 63.4%, while the prevalence found by Zamani et al. [28] was 59.3%. Several studies performed on Alaska Native people highlighted that gastric cancer remains the third most frequent cause of cancer-related death in this population [29][30][31], three times higher than among US whites [32]. Moreover, in this area, 75% of the people were found to have positive H. pylori IgG antibodies, considerably increasing their risk of developing gastric cancer [33,34] based on the close relationship between this infection and gastric carcinogenesis. ...
Helicobacter pylori is usually acquired during childhood. The reports from the last two decades pointed out a decrease in H. pylori prevalence across geographical areas worldwide compared to previously reported data. Most of the studies performed in America found an overall H. pylori infection prevalence of approximately 50%. The most important risk factors in America include being male, poor adherence or difficult access to treatment, and the lack of in-home water service. Despite the descending trend in prevalence worldwide, the overall prevalence in Africa remains very high (70%). Nevertheless, the prevalence of H. pylori in children without gastrointestinal who underwent screening was reported to be only 14.2%. The main risk factors in Africa are having a traditional pit or no toilet, poverty, birth order, source of drinking water, or being a farmer. Asia seems to have the widest variations in terms of H. pylori prevalence. Several risk factors were reported in Asia to be associated with this infection, such as lower income and educational level, house crowding, rural residence, ethnicity, the use of tanks as water supplies, alcohol drinking, active smoking, eating spicy food or raw uncooked vegetables, poor living conditions and sanitation. The overall prevalence of H. pylori infection in European children is almost 25%. Portugal has the highest prevalence of all European countries at 66.2% in children 13 years of age. The risk factors in European individuals consist of living in rural areas, eating unwashed fruits and vegetables, not washing hands after school, low parental education and unemployment, and short education duration. Further studies are required to identify the precise mechanisms involved in the discrepancies of H. pylori prevalence worldwide.
... Les facteurs socio-économiques entrent aussi en jeux dans la probabilité de développer un cancer gastrique : le taux de mortalité est inversement corrélé au revenu national médian par habitant (176). La diminution de la mortalité par cancer gastrique est associée à l'amélioration du sucres. ...
L’infection par la bactérie Helicobacter pylori touche la moitié de la population mondiale et est la principale cause à l’origine des adénocarcinomes gastriques, faisant du cancer de l’estomac la troisième cause de mortalité par cancer dans le monde. Des études précédentes ont montré que H. pylori, via son oncoprotéine CagA, est capable d’induire une transition épithélio-mésenchymateuse (EMT) conduisant à l’émergence de cellules possédant des propriétés de cellules souches cancéreuses (CSCs). Les CSCs représentent une population rare de cellules au sein des tumeurs, exprimant le marqueur de CSCs CD44+. Elles sont à l’origine de l’initiation tumorale, de la persistance et de la propagation des cellules cancéreuses au sein de l’organisme. Récemment, le laboratoire a mis en évidence une sous-population de CSCs gastriques dotées de propriétés invasives et exprimant le variant CD44v3. La voie de signalisation Hippo, impliquée dans l’organogenèse, le maintien de l’homéostasie tissulaire et a été impliquée dans le contrôle des propriétés des cellules souches saines et cancéreuses dans certains organes. Elle s’articule autour de kinases, MST1/2 et LATS1/2, responsables de la répression des oncogènes YAP et TAZ. Lorsque cette voie est inactive, l’activité transcriptionnelle du complexe YAP/TAZ-TEAD conduit à l’expression de programmes transcriptionnels impliqués dans la survie et la croissance cellulaire. Les objectifs de ces travaux ont été de déterminer le rôle des éléments de la voie de signalisation Hippo dans 1) l’émergence des CSCs induites par l’infection à H. pylori et 2) les propriétés tumorigéniques et invasives des CSCs gastriques. Des expériences de co-culture avec H. pylori réalisées in vitro ainsi que d’immunomarquages de muqueuse gastrique de patients infectés ou non, ont permis de démontrer que l’infection par H. pylori induit une dérégulation de la voie Hippo et l’augmentation d’expression et d’activation des oncogènes YAP et TAZ in vitro et in vivo. L’étude des conséquences fonctionnelles du ciblage de la voie de signalisation LATS2/YAP/TAZ a mis en évidence que l’activation de YAP et TAZ par H. pylori, participe à l’induction de l’EMT à la transformation de la muqueuse gastrique lors de la métaplasie intestinale et à l’émergence des CSCs gastriques. H. pylori est également responsable de l’activation de la boucle de rétrocontrôle négatif qui s’opère entre YAP et LATS2, conduisant LATS2 à atténuer la carcinogenèse gastrique. L’étude du ciblage de TAZ par interférence à ARN, a permis de montrer son implication dans la formation de tumorsphères, l’invasion et l’expression du marqueur de CSCs invasives CD44v3. Ainsi, l’activation de TAZ confère aux cellules des propriétés de CSCs invasives en réponse à l’infection par H. pylori. L’étude de l’expression de TAZ dans les tissus gastriques de patients a permis de mettre en évidence une plus forte expression de TAZ dans les tissus tumoraux qui serait associée à l’expression du marqueur de CSCs invasives CD44v3 et à l’agressivité des tumeurs. Pour conclure, ces travaux de thèse démontrent l’implication de la voie de signalisation Hippo/YAP/TAZ dans la carcinogenèse gastrique induite par H. pylori. Ces travaux ont permis pour la première fois d’identifier la protéine TAZ comme étant un acteur majeur de contrôle des propriétés tumorigéniques et invasives des CSCs gastriques. Ces résultats nous ont également permis de mettre en évidence l’existence d’une sous-population de CSCs fortement agressive exprimant CD44v3 et TAZ.
... Gastric cancer (GC) is the fifth most common cancer and third leading cause of cancer deaths worldwide, especially in Eastern Europe, South America, and Eastern Asia (mainly China, Japan, and Korea) [1][2][3][4]. However, gastric cancer incidence has decreased markedly in Asian countries in recent years [5]. ...
Background: Abnormal regulation of genes has been closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. In our study, we used RNA sequencing analyses to show that on gastric cancer tissues to identification of gastric cancer prognostic markers. We specifically chose to study RNF43 because it inhibits gastric cancer-related Wnt/β-catenin signaling by interacting with Wnt receptors. PWWP2B was chosen because it is a gene which is downregulated in gastric cancer.
Methods: Utilizing RNA sequencing analysis, we evaluated the mRNA expression profile in gastric cancer patients. Also, we used HAP1 cells which is a human near-haploid cell line derived from the male chronic myelogenous leukemia cell line KBM-7. These cell line has one copy of each gene, ensuring the edited allele will not be masked by additional alleles. We investigated the screening of 1,449 FDA-approved drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells. RNA sequencing data reveals that RNF43 and PWWP2B expression were down-regulated in recurrence gastric cancer patients. Next, we investigated the anti-cancer effects of selected drugs in RNF43 and PWWP2B down-regulated MKN45 gastric cancer cells and xenograft model.
Results: Among these FDA-approved drugs, three drugs (docetaxel trihydrate, pelitinib and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. In MKN45 xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group. Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer.
Conclusions: Our findings suggest that docetaxel trihydrate, uprosertib and pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with a decrease in RNF43 and PWWP2B expression.
... Stomach cancer is the third fatal sickness among diseases and the fifth most common cancer around the world [1]. In recent years, stomach cancer is a critical sickness and general medical issue around the world [2]. This disease naturally grows slowly over many years and is also known as gastric cancer. ...
Background: Stomach cancer is known as gastric cancer. Knowing any disease risk factors is an important task which is varied from country to country. In this study, we aim to find out all possible preoperative significant risk factors for stomach cancer and increase awareness among the people of Bangladesh. Methodology: Personal interview methods have been applied and the same questionnaire is maintained to collect Case and Control Group Data. The total number of sample size is 300 (Case = 150 and Control = 150). Case group people’s data are collected from the National Institute of Cancer Research and Hospital (NICRH) Bangladesh and Control groups data are collected from outside of the hospital. The entire analysis took place by frequency distribution with P-value and finally doing binary logistic regression modeling by odds ratio. Results: After analyzing 300 subjects’ records with 26 risk factors, we have received 21 statistically significant (P< 0.05) risk factors where “Skin Color Turn into Pale” including (P<0.001, OR =139.462), and “Abdominal Pain” are the first and second most pre-operative risk factors of stomach cancer including (P<0.001, OR = 66.769). Besides, we have found other significant high-risk factors like “Age”, “BMI”, “Education Level”, “Get Ill Too Much (frequently affected by the disease)”, “Working Status”, “Monthly Income”, “Family Member”, “Blood Group”, “Daily Food Intime”, “Take Spicy and Salted Food”, “Menetrier Disease”, “Previous Stomach Surgery” and so on. Conclusion The investigated outcomes of this study will help to increase awareness among the people of Bangladesh as well as the rest of the world.
... Gastric cancer is the fifth most common cancer and third leading cause of cancer deaths worldwide, especially in Eastern Europe, South America, and Eastern Asia (mainly China, Japan, and Korea) [1][2][3]. ...
Background
The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. In our study, we have performed RNA sequencing analysis on gastric cancer tissues that decreased levels of RNF43 and PWWP2B were significantly associated with recurrence (11/11, 100%, P < 0.001). Therefore, we investigated the screening of 1,449 FDA-approved drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells.
Methods
We demonstrated that RNF43 KO and PWWP2B KO cells showed significantly increased proliferation and migration abilities. Next, we investigated the inhibitory effects of 1,449 drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells.
Results
Among these FDA-approved drugs, three drugs (docetaxel trihydrate, pelitinib and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. In RNF43 and PWWP2B down-regulated MKN45 xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group. Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer.
Conclusion
Our findings suggest that docetaxel trihydrate, uprosertib and pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with an aberrant decrease in RNF43 and PWWP2B expression.
... especially in Eastern Europe, South America, and Eastern Asia (mainly China, Japan, and Korea) [1][2][3]. ...
Background: Abnormal regulation of genes was closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs.
Methods: In our study, we have performed RNA sequencing analysis on gastric cancer tissues that decreased levels of RNF43 and PWWP2B were significantly associated with recurrence. RNF43 inhibit gastric cancer-related Wnt/β-catenin signaling by interacting with Wnt receptors. PWWP2B is unknown gene which is downregulated in gastric cancer. Therefore, we investigated the screening of 1,449 FDA-approved drugs in male-derived human cell lines such as HAP1, HAP1 RNF43 KO, and HAP1 PWWP2B KO and female-derived human cell line such as SNU620 cells.
Results: We demonstrated that RNF43 KO and PWWP2B KO cells showed significantly increased proliferation and migration abilities. Next, we investigated the inhibitory effects of 1,449 drugs in HAP1, HAP1 RNF43 KO, HAP1 PWWP2B KO, and SNU620 cells. After the first round of screening, candidate drugs were selected based on an inhibition rate of > 60% loss of viability compared to wild type cells. Among these FDA-approved drugs, nine drugs (aprepitant, docetaxel trihydrate, ethinyl estradiol, griseofulvin, INC280, pelitinib, pimobendan, tepotinib, and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. Migration and apoptosis analyses demonstrated that docetaxel trihydrate and pelitinib showed the best inhibition and apoptotic rates, with the smallest half maximal inhibitory concentrations among the screened candidate drugs. In a murine xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group, when administered by oral gavage.
Conclusions: Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer. Our findings suggest that pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with an aberrant decrease in RNF43 and PWWP2B expression.
... The rate of gastric cancer (GC) incidence is high in East Asia, Eastern Europe, and South America. [1][2][3] Mortality rates have decreased markedly in recent years; 4 however, GC remains the third most common cancer, causing 12% of all cancer-related deaths every year. 5,6 To develop and identify new drug candidates with the aim of reducing GC mortality rates, it is important to determine its tumor characteristics and treatment parameters. ...
Purpose:
CD44 isoforms are highly expressed in cancer stem cells, initiating tumor growth and sustaining tumor self-renewal. Among these isoforms, CD44 variant 9 (CD44v9) is overexpressed in chronic inflammation-induced cancer. CD44 and the mesenchymal-to-epithelial transition (MET) receptor tyrosine kinase are coactivated in some gastric cancers (GCs). In this study, we characterized MET and CD44 expression and signaling in human GC cell lines and analyzed differences in the susceptibility of these lines to foretinib.
Patients and methods:
We analyzed cell viability and the rate of apoptotic cells using MTS assays and flow cytometry, respectively. Gene and protein expression were assessed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunoblotting, respectively.
Results:
Foretinib treatment resulted in dose-dependent inhibition of growth in c-MET-amplified MKN45 and SNU620 cells with concomitant induction of apoptosis, but not in c-MET-reduced MKN28 and AGS cells. Foretinib treatment also significantly reduced phosphor-c-MET, phosphor-AKT, beta-catenin, and COX-2 protein expression in MKN45 and SNU620 cells. Interestingly, foretinib significantly reduced CD44, CD44v9, COX-2, OCT3/4, CCND1, c-MYC, VEGFA, and HIF-1a gene expression in CD44 and MET coactivated MKN45 cells and increased CD44s gene expression; in contrast, these drugs were only slightly active against SNU620 cells.
Conclusion:
The results of this study indicate that foretinib could be a therapeutic agent for the prevention or treatment of GCs positive for CD44v9 and c-MET.
... Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide [1,2]. With improvements in diagnostic surveillance, advanced surgical techniques, and improved chemotherapeutic and targeted agents, the survival of patients with GC has been extended. ...
Background:
Protein tyrosine phosphatase receptor delta (PTPRD) is frequently inactivated in various types of cancers. Here, we explored the underlying mechanism of PTPRD-loss-induced cancer metastasis and investigated an efficient treatment option for PTPRD-inactivated gastric cancers (GCs).
Methods:
PTPRD expression was evaluated by immunohistochemistry. Microarray analysis was used to identify differentially expressed genes in PTPRD-inactivated cancer cells. Quantitative reverse transcription (qRT-PCR), western blotting, and/or enzyme-linked immunosorbent assays were used to investigate the PTPRD-CXCL8 axis and the expression of other related genes. An in vitro tube formation assay was performed using HUVECs. The efficacy of metformin was assessed by MTS assay.
Results:
PTPRD was frequently downregulated in GCs and the loss of PTPRD expression was associated with advanced stage, worse overall survival, and a higher risk of distant metastasis. Microarray analysis revealed a significant increase in CXCL8 expression upon loss of PTPRD. This was validated in various GC cell lines using transient and stable PTPRD knockdown. PTPRD-loss-induced angiogenesis was mediated by CXCL8, and the increase in CXCL8 expression was mediated by both ERK and STAT3 signaling. Thus, specific inhibitors targeting ERK or STAT3 abrogated the corresponding signaling nodes and inhibited PTPRD-loss-induced angiogenesis. Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression.
Conclusions:
Thus, the PTPRD-CXCL8 axis may serve as a potential therapeutic target, particularly for the suppression of metastasis in PTPRD-inactivated GCs. Hence, we propose that the therapeutic efficacy of metformin in PTPRD-inactivated cancers should be further investigated.
... High-incidence areas of GC include Eastern Europe, South America, and East Asia [1][2][3]; however, the mortality rates have decreased markedly in recent years [4]. In Korea, despite a decline in the incidence of GC, it remains the second most common cancer [5]. ...
Objective
Gastric cancer is more open related to genetic predisposition. In our RNA sequencing study on gastric cancer patients, Runt-related transcription factor-3 (RUNX3) expression was significantly down-regulated in gastric cancer. We showed that decreased levels of RUNX3 are significantly associated with c-MET (r = − 0.4216, P = 0.0130). In addition, c-MET expression is a candidate for targeted therapy in gastric cancer. Therefore, in the present study, the anti-cancer effects of the c-MET inhibitor on gastric cancer cells from positive or negative for c-MET amplification were evaluated.
Results
INC280 treatment inhibits growth of a c-MET-amplified MKN45 (RUNX3-positive) and SNU620 (RUNX3-negative) diffuse type cells. Then, INC280 showed the highest inhibition and apoptotic rates with the lowest IC50s in MKN45 cells but not in c-MET-reduced MKN28 (intestinal type) cells. We also showed that INC280 inhibits the WNT signaling pathway and SNAIL expression in MKN45 cells. The data indicate that INC280 could be used as therapeutic agents for the prevention or treatment of diffuse gastric cancer positive for c-MET amplification.
Electronic supplementary material
The online version of this article (10.1186/s13104-019-4163-x) contains supplementary material, which is available to authorized users.
... Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide [1,2]. Although the incidence of GC and mortality associated with this disease has gradually decreased in Japan and Korea, it still remains the second leading cause of death in Korea [3]. ...
Calponin 3 (CNN3) is an F-actin-binding protein that regulates actin cytoskeletal rearrangement. However, the role of CNN3 in cancer cell invasion and resistance to chemotherapeutic agents has not yet been investigated. The present study was undertaken to investigate whether CNN3 influences cancer-related phenotypes in gastric cancer. We demonstrate that CNN3 contributes to cell invasion and resistance to doxorubicin in gastric cancer. CNN3 expression was markedly elevated in highly invasive cancer cell lines compared to less invasive or noninvasive cancer cell lines. Depletion of CNN3 protein suppressed the invasive ability of gastric cancer cells. The highly invasive MKN-28 gastric cancer cells were more resistant to doxorubicin than the noninvasive MKN-45 cells; however, knockdown of CNN3 expression in MKN-28 cells resensitized them to doxorubicin treatment. Taken together, our results suggest that CNN3 plays a key role in invasiveness and doxorubicin resistance in gastric cancer cells.
... This may be due to the fact that they have no major risk factors in common with gastric cancer. 28 Furthermore, individuals with higher socioeconomic level have lower gastric cancer incidence than those with lower socioeconomic level, 29 whereas the incidence of breast and prostate cancer increases with higher socioeconomic level. 30 Although the sample was obtained from RORENO, which is representative of Northern Portuguese cancer survivors, our results on the incidence of gastric SPCs may not be representative of all of Portugal as the North has higher incidence rates of gastric cancer compared to the rest of the country, 9 thus extrapolating our results to the rest of the country should be done cautiously. ...
Objective
To compare the incidence rates of gastric cancer among cancer survivors with those in the general population, and estimate the probability of a gastric second primary cancer being diagnosed 10 years after any other first primary cancer.
Method
A cohort of first primary cancers (other than gastric) diagnosed in Northern Portugal between 2000 and 2006 (n = 64,648) was followed until 31/12/2012 for gastric second primary cancers. Incidence rates, standardized incidence ratios and the cumulative incidence of gastric second primary cancers were calculated.
Results
Overall, 330 patients developed gastric second primary cancers (21.2% within two months). The incidence rate of gastric second primary cancers was higher within two months of the first primary cancer (standardized incidence ratios: 5.20 in males and 7.89 in females), particularly among survivors of cancers of the oesophagus, colon and rectum, than in the remaining period (standardized incidence ratios: 0.64 in males and 0.74 in females). The 10-year risk of a gastric second primary cancer was 0.6% (males: 0.7%; females: 0.4%).
Conclusion
The incidence rate of gastric second primary cancers among cancer survivors was higher than in the general population only soon after the first primary cancer, and lower thereafter. Despite the high mortality, the probability of a gastric second primary cancer within 10-years of the first primary cancer was 0.6%.
... Gastric cancer (GC), a malignant tumor of the digestive system, is the second leading cause of cancer-related death and the fourth most common cancer worldwide (80). Although its incidence and mortality have appreciably decreased globally over recent decades, the mortality of GC is still relatively high in Asia (81). ...
Cancer is the second leading cause of mortality worldwide. More importantly, the mortality rates for cancer are increasing. In China, lung cancer, liver cancer and gastric cancer are the top three leading causes of mortality in males, whereas lung cancer, gastric cancer and liver cancer are ranked the top three causes of mortality in females. Exosomes are extracellular vesicles that are produced and released by many different cells; these vesicles have a size range between 30 and 100 nm in diameter, and contain a lipid bilayer. Exosomes exist in various bodily fluids, contain plentiful amounts of nucleic acids and proteins, and shuttle these materials between cells to mediate the development of cancers. The present review summarizes the composition of exosomes and methods for their isolation and then intensively highlights the latest findings on the contributions of exosomal microRNAs (miRNAs) and proteins to lung cancer, liver cancer and gastric cancer. Taken together, exosomal miRNAs and proteins may be used as noninvasive, novel biomarkers for cancer diagnosis, prognosis or precision treatment owing to their ability to promote tumor progression and metastasis, and their ability to regulate the immune response and tumor cell sensitivity to chemotherapy drugs.
... Gastric cancer remains one of the leading causes of cancerrelated death in several countries in Asia, Latin America, and Central and Eastern Europe [8,9]. Although surgical resection is effective in the early stage of gastric carcinoma (GC), additional treatment is necessary for advanced cases. ...
The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.
... In Portugal, gastric cancer ranks fifth in both incidence and mortality (Ferlay et al., 2013), although the latter has a decreasing trend in recent decades (Morais et al., 2016). The rates in Portugal are among the highest in Europe ( Peleteiro et al., 2014), and there is a large variation within the country, with incidence and mortality being considerably higher in the North (Lunet, 2011;Morais et al., 2016). ...
To quantify the association between prediagnosis lifestyles with the risk of second primary cancers (SPCs) and survival of patients with gastric first primary cancer (FPC). We recruited 574 gastric patients from two major public hospitals in North Portugal (2001-2006). Smoking, alcohol and dietary habits in the year before FPC diagnosis were evaluated. Patients were followed up to 31 December 2011 for an SPC and to 31 May 2017 for vital status. Cox proportional hazards regression was used to estimate adjusted hazard ratios for incidence of an SPC or death. During follow-up, SPCs were diagnosed in five women and 23 men, and 409 patients died, corresponding to an estimated 10-year cumulative incidence of 5.2% for SPC and an estimated 15-year cumulative mortality of 72.1%. A significantly higher hazard ratio (95% confidence interval) for SPCs was observed in patients reporting a higher consumption of red and processed meat versus the lowest third (4.49: 1.31-15.37), and for mortality in those with heavy alcohol intake versus never drinkers (1.73: 1.00-2.99) and excess weight versus normal weight (1.31: 1.04-1.65); no other significant associations were observed according to prediagnosis lifestyle. Prediagnosis lifestyles may affect the occurrence of an SPC and survival among gastric FPC survivors in the long term.
... Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide 1,2 . Histologically, GCs are classified as glandforming intestinal-type GC (IGC) and scattered-cell diffuse-type GC (DGC) by the Lauren classification 3 . ...
Diffuse-type gastric cancer (DGC) is a GC subtype with heterogeneous clinical outcomes. Lymph node metastasis of DGC heralds a dismal progression, which hampers the curative treatment of patients. However, the genomic heterogeneity of DGC remains unknown. To identify genomic variations associated with lymph node metastasis in DGC, we performed whole exome sequencing on 23 cases of DGC and paired non-tumor tissues and compared the mutation profiles according to the presence (N3, n = 13) or absence (N0, n = 10) of regional lymph node metastasis. Overall, we identified 185 recurrently mutated genes in DGC, which included a significant novel mutation at CMTM2, as well as previously known mutations at CDH1, RHOA, and TP53. Noticeably, CMTM2 expression could predict the prognostic outcomes of DGC but not intestinal-type GC (IGC), indicating pivotal roles of CMTM2 in DGC progression. In addition, we identified a recurrent loss of heterozygosity (LOH) of DNA copy numbers at the 3p12-pcen locus in DGC. A comparison of N0 and N3 tumors showed that N3 tumors exhibited more frequent DNA copy number aberrations, including copy-neutral LOH and mutations of CpTpT trinucleotides, than N0 tumors (P = 0.2 × 10-3). In conclusion, DGCs have distinct profiles of somatic mutations and DNA copy numbers according to the status of lymph node metastasis, and this might be helpful in delineating the pathobiology of DGC.
... 15 Gastric cancer incidence and mortality are decreasing in many parts of the world, but this is not true for Alaska Native people for whom gastric cancer is the third most common cause of cancerrelated death. [16][17][18] Additionally, the gastric cancer mortality rate among Alaska Native people is more than three times higher than among U.S. whites (11.3 vs 3.2 per 100 000 persons). 19 Past studies in Alaska have shown that H. pylori -infected persons have a higher risk of gastric cancer compared with noninfected persons and that 75% of Alaska Native people have H. pylori IgG antibodies. ...
Background:
Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection.
Methods:
A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old.
Results:
We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered.
Conclusions:
Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.
... Gastric cancer (GC) is the fourth most common cancer worldwide and, although rates have been declining by approximately 2% per year, it is responsible for the second highest rate of cancer-related morbidity and mortality (Bertuccio et al., 2009;Bosetti et al., 2013;Peleteiro et al., 2014). The clinical outcomes for patients with advanced gastric cancer are poor, despite the significant efforts that have been devoted to the development of therapeutic treatments (De Martel, Forman & Plummer, 2013;Karimi et al., 2014). ...
Gastric cancer (GC) is a complex disease with heterogeneous genetic mechanisms. Genomic mutational profiling of gastric cancer not only expands our knowledge about cancer progression at a fundamental genetic level, but also could provide guidance on new treatment decisions, currently based on tumor histology. The fact that precise medicine-based treatment is successful in a subset of tumors indicates the need for better identification of clinically related molecular tumor phenotypes, especially with regard to those driver mutations on tumor suppressor genes (TSGs) and oncogenes (ONGs). We surveyed 313 TSGs and 160 ONGs associated with 48 protein coding and 19 miRNA genes with both TSG and ONG roles. Using public cancer mutational profiles, we confirmed the dual roles of CDKN1A and CDKN1B. In addition to the widely recognized alterations, we identified another 82 frequently mutated genes in public gastric cancer cohort. In summary, these driver mutation profiles of individual GC will form the basis of personalized treatment of gastric cancer, leading to substantial therapeutic improvements.
... Gastric cancer is the fourth most common cancer and is the third leading cause of cancer, with more than 700,000 deaths every year all over the world [1][2][3]. Despite the declined incidence and mortality due to the major improvements in diagnosis and treatment, there are less than 20% of patients with gastric cancer surviving up to 5 years [1]. ...
Retinoid-related orphan receptor α (RORα) is a nuclear receptor, which regulates inflammation and immune responses, lipid metabolism and circadian rhythm. Although RORα suppresses breast tumor invasion, it is unknown whether RORα is dysregulated in gastric cancer leading to cellular survival. Therefore, we hypothesize that RORα is dysfunctional in gastric carcinoma and this causes decreased apoptosis in gastric cancer cells. To test this hypothesis, we employed human gastric cancer tissues with different stages to determine RORα expression, as well as in vitro human gastric cancer cells to determine how RORα is reduced during apoptosis. We found that the expression of RORα was reduced in gastric tissues with cancer, and this correlated with increased TNM stages. The mechanisms underlying RORα reduction is due to the reduced activation of AMP-activated protein kinase (AMPK), as a selective AMPK activator AICAR increased RORα activation and level in human gastric cancer cells. Furthermore, AICAR treatment increased RORα recruitment on the promoters of tumor suppressor genes (i.e., FBXM7, SEMA3F and p21) leading to apoptosis in human gastric cancer cells. Taken together, RORα reduction occurs in gastric cancer leading to the survival of tumor cells, which is attenuated by AMPK. Therefore, both RORα and AMPK are potential targets for the intervention and therapy in gastric carcinoma.
... Gastric cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide (1) , despite the sustained decline in gastric cancer rates over the past several decades (2,3) . The apparent potential for an even greater decrease without specific interventions to control its main determinants contributes to the misperception that gastric cancer may no longer be an important public health concern, at least in more developed countries. ...
Assessing the impact that patterns of Na intake may have on gastric cancer will provide a more comprehensive estimation of Na reduction as a primary prevention approach. We aimed to estimate the proportion of gastric cancer cases that are attributable to Na intake above the recommendation by the WHO (≤2 g/d) throughout the world in 2010, as well as expected values for 2030. Population attributable fractions (PAF) were computed for 187 countries, using Na intakes in 1990 and 2010 and estimates of the association between Na intake and gastric cancer, assuming a time lag of 20 years. Median PAF ranged from 10·1% in low to 22·5 % in very high Human Development Index (HDI) countries in men (
P
<0·001) and from 7·2 to 16·6 %, respectively, among women (
P
<0·001). An increase in median PAF until 2030 is expected in most settings, except for countries classified as low HDI, in both sexes. High Na intakes account for a large proportion of gastric cancer cases, and proportions are expected to increase in almost all of the countries. Intensified efforts to diminish Na intake in virtually all populations are needed to further reduce gastric cancer burden.
... Gastric cancer is the fifth most common malignancy and the third leading cause of death by cancer worldwide (1) . Despite the declining incidence and mortality rates for several decades (2) , in the most recent years, the relative declines were smaller in several settings, and a levelling off is already expected in a few countries (3) . ...
The regional and temporal variation in patterns of fruit and vegetable intake contributes to differences in the impact on gastric cancer burden across regions and over the years. We aimed to estimate the proportion and absolute number of gastric cancer cases that could have been prevented in 2012 with an increase in fruit and vegetable intake up to the levels defined by the Global Burden of Disease as the theoretical minimum-risk exposure distribution (300 and 400 g/d, respectively), as well as the corresponding figures expected for 2025. Preventable fractions (PF) were computed for 161 countries, using data on fruit and vegetable availability in 1997 and 2010 and published estimates of the magnitude of the association between fruit and vegetable intake and gastric cancer, assuming a time lag of approximately 15 years. Countries classified as very high Human Development Index (HDI) presented median PF in 2012 much lower than low-HDI countries for both fruits (3·0
v.
10·2 %,
P
<0·001) and vegetables (6·0
v.
11·9 %,
P
<0·001). For vegetables only, PF significantly decreased until 2025 in most settings; however, this corresponded to a reduction in the absolute number of preventable gastric cancer cases in less than half of the countries. Increasing fruit and vegetable intake would allow preventing a relatively high proportion of gastric cancer cases, mostly in developing countries. Although declines in PF are predicted in the near future, changes in order to achieve healthier lifestyles may be insufficient to overcome the load of demographic variation to further reduce the gastric cancer burden.
... As the majority of patients have poor outcomes, it is crucial to understand the molecular mechanisms for GC and develop more effective therapeutic strategies. Here, we give an overview of the roles of lncRNAs as ceRNAs in GC. patterns in GC vary substantially across geographical regions [22,23], reflecting an uneven distribution of the key factors for GC incidence and mortality across different countries. The incidence and mortality of GC have decreased, mainly because of the reduction in the prevalence of Helicobacter pylori infection and smoking, and to the improvements in food preservation for the past years. ...
Long noncoding RNA (lncRNA) is >200 nucleotides long and lacks coding ability. LncRNA was regarded as transcript noise, until
emerging results showed its roles in development, homeostasis and carcinogenesis. LncRNAs containing microRNA (miRNA) response
elements could compete with the miRNA target gene and regulate its expression through decreasing free functional miRNA. Such
lncRNA is called competing endogenous RNA (ceRNA), and the ‘lncRNA–miRNA’ interaction appreciably enriches the world of RNA–RNA
regulation. Gastric cancer involves dysregulation of both protein-coding genes and noncoding genes, and the ceRNA regulatory
mechanism may participate in this pathogenic process. In this review, we discuss recent findings on the roles of ceRNAs in
gastric carcinogenesis.
... The decline in mortality rates found in Portugal, without meaningful changes in survival, reflects the decrease in gastric cancer incidence, supported by lower risk factor prevalence, namely, H. pylori infection. In countries presenting low gastric cancer rates, the prevalence of H. pylori has long been decreasing, but the decline is more recent in settings with high gastric cancer incidence (Peleteiro et al., 2014a(Peleteiro et al., , 2014b. Although it was our aim to draw a parallel between the prevalence of H. pylori and the gastric cancer mortality trends, the data available for Portugal do not allow a direct comparison. ...
Portugal has the highest gastric cancer mortality rates in Western Europe, along with high prevalences of Helicobacter pylori infection. Monitoring their trends is essential to predict the burden of this cancer. We aimed to quantify time trends in gastric cancer mortality in Portugal and in each administrative region, and to compute short-term predictions, as well as to describe the prevalence of H. pylori infection, through a systematic review. Joinpoint analyses were used to identify significant changes in sex-specific trends in gastric cancer age-standardized mortality rates (ASMR) and to estimate annual percent changes (APC). The most recent trends were considered to compute estimates up to 2020 by adjusting Poisson regression models. We searched PubMed and IndexRMP to identify studies carried out in Portugal reporting the prevalence of H. pylori. Gastric cancer mortality has been decreasing in Portugal since 1971 in men (from ASMR=55.3/100 000; APC=-2.4, 95% confidence interval: -2.5 to -2.3) and since 1970 in women (from ASMR=28.0/100 000; APC=-2.8, 95% confidence interval: -2.9 to -2.7), although large regional differences were observed. Predicted ASMR for 2015 and 2020 were 18.8/100 000 and 16.7/100 000 for men and 8.5/100 000 and 7.4/100 000 for women, respectively. The prevalence of H. pylori varied from almost 5% at 0.5-2 years to just over 90% at 70 years or more. No consistent variation was observed since the 1990s. The downward trends in mortality rates are expected to remain in the next decades. The high prevalence of H. pylori infection across age groups and studies from different periods shows a large potential for decrease in the burden of gastric cancer in Portugal.
... Gastric cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide [1], despite the sustained decline of gastric cancer rates over the past several decades [2, 3]. The apparent potential for an even greater decrease without specific interventions to control its main determinants contributes to the misperception that this is no longer a public health problem, at least in more developed countries. ...
The heterogeneous patterns and trends in tobacco consumption contribute to regional and gender differences in the burden of gastric cancer attributable to smoking.
To estimate the proportion and absolute number of gastric cancer cases that can be attributed to smoking in different countries, in 2012 and 2020.
Population attributable fractions (PAFs) were computed for 118 countries, using data of smoking prevalence in 2002 and 2011 and published estimates of the magnitude of the association between smoking and gastric cancer, assuming a time lag of ≈10 years.
For men, the highest PAF estimates in 2012 were observed in Eastern Asia and the lowest in North America, whereas for women the highest were in Western Europe and the lowest in Africa. Very high Human Development Index (HDI) countries presented the lowest median PAF in men (very high vs. high, medium, and low HDI: 17.2 vs. 20.8 %, p = 0.014) and the highest median PAF in women (very high vs. high, medium, and low HDI: 4.3 vs. 1.8 %, p < 0.001). Estimates for 2020 show a decrease in median PAFs, but the estimated absolute number of cases attributable to smoking in the countries analyzed increased for men (≈154,000 vs. ≈160,000) and decreased for women (≈6200 vs. ≈5600).
Smoking accounts for a larger number of gastric cancer cases among men, and gender differences are expected to increase in the next decade, despite the decrease in PAFs. Intensified efforts to control smoking are needed to further reduce the burden of gastric cancer.
... Gastric cancer is the fifth most common malignancy in the world and the third leading cause of cancer mortality worldwide [1]. Incidence and mortality rates have been diminishing for several decades [2,3], mostly due to the decrease in the frequency of cancers of the "intestinal" histological type [4,5], which account for approximately up to three-quarters of the total [4,[6][7][8][9]. However, recent trends show that in some countries the declines are becoming less marked [3]. ...
Background
The evaluation of specific risk factors for early endpoints in the gastric carcinogenesis pathway may further contribute to the understanding of gastric cancer aetiology.
Aims
To quantify the relation between smoking and intestinal metaplasia through systematic review and meta-analysis.
Methods
Articles providing data on the association between smoking and intestinal metaplasia were identified in PubMed®, Scopus® and Web of Science™, searched until April 2014, and through backward citation tracking. Summary odds ratio estimates and 95% confidence intervals were computed using the DerSimonian and Laird method. Heterogeneity was quantitatively assessed using the I2 statistic.
Results
A total of 32 articles were included in this systematic review and 19 provided data for meta-analysis. Smoking was defined as ever vs. never (crude estimates, six studies, summary odds ratio = 1.54, 95% confidence interval: 1.12–2.12, I2 = 67.4%; adjusted estimates, seven studies, summary odds ratio = 1.26, 95% confidence interval: 0.98–1.61, I2 = 65.0%) and current vs. non-smokers (crude estimates, seven studies, summary odds ratio = 1.27, 95% confidence interval: 0.88–1.84, I2 = 73.4%; adjusted estimates, two studies, summary odds ratio 1.49, 95% confidence interval: 0.99–2.25, I2 = 0.0%).
Conclusion
The weak and non-statistically significant association found through meta-analysis of the available evidence does not confirm smoking as an independent risk factor for intestinal metaplasia.
Gastric cancer (GC) is among the leading causes of cancer-related deaths worldwide. The discovery of robust diagnostic biomarkers for GC remains a challenge. This study sought to identify biomarker candidates for GC by integrating machine learning (ML) and bioinformatics approaches. Transcriptome profiles of patients with GC were analyzed to identify differentially expressed genes between the tumor and adjacent normal tissues. Subsequently, we constructed protein-protein interaction networks so as to find the significant hub genes. Along with the bioinformatics integration of ML methods such as support vector machine, the recursive feature elimination was used to select the most informative genes. The analysis unraveled 160 significant genes, with 88 upregulated and 72 downregulated, 10 hub genes, and 12 features from the variable selection method. The integrated analyses found that EXO1, DTL, KIF14, and TRIP13 genes are significant and poised as potential diagnostic biomarkers in relation to GC. The receiver operating characteristic curve analysis found KIF14 and TRIP13 are strongly associated with diagnosis of GC. We suggest KIF14 and TRIP13 are considered as biomarker candidates that might potentially inform future research on diagnosis, prognosis, or therapeutic targets for GC. These findings collectively offer new future possibilities for precision/personalized medicine research and development for patients with GC.
BackgroundsGastric cancer (GC), a prevalent malignancy in Eastern Asia, is associated with aberrant transcriptional regulation.
Objective
Here, we evaluated the mRNA and microRNA transcriptomes in patients with gastric cancer to gain insight into the molecular underpinnings of this disease.ResultsWe observed upregulation of inhibin βA (INHBA), CDC7, SULF1, COL11A1, KIAA1199, and CLDN1 transcripts in gastric cancer and showed that INHBA upregulation was associated with cancer recurrence. Expression of has-miR-135a-5p was significantly lower in gastric cancer tissues compared with matched normal tissues and was inversely associated with INHBA expression.Conclusion
Our findings suggest that INHBA and has-miR-135a-5p expression serve as therapeutic markers of gastric cancer recurrence.
Background:
Gastric cancer (GC) is one of the most common malignant diseases worldwide, the incidence and mortality for GC is still high, thus it is urgently important to identify the effective and reliable biomarkers to evaluate GC and the underlying molecular events.
Methods:
The study integrated four Gene Expression Omnibus (GEO) profile datasets and The Cancer Genome Atlas (TCGA) dataset to screen differentially expressed genes (DEGs), screened key genes by performing the Kaplan-Meier analysis, univariate and multivariate-cox analysis. Further analysis were performed to evaluate and validate the prognostic value of the key genes based on TCGA database and online websites. In addition, mechanism analysis of the key genes was performed thought biological processes and KEGG pathway analysis.
Results:
In the study, 192 DEGs (92 up-regulated and 100 down-regulated) were identified from the GEO and TCGA datasets. Next, gene ontology (GO) for DEGs focused primarily on cell adhesion, extracellular region and extracellular matrix structural constituent. Then four significant key genes were screened by performed the Kaplan-Meier analysis, univariate and multivariate-cox analysis. By using Kaplan-Meier plotter and OncoLnc, the expression level was associated with a worse prognosis. In addition, the area under curve (AUC) for time-dependent receiver operating characteristic (ROC) indicated a moderate diagnostic value. Furthermore, the expression of collagen triple helix repeat containing 1 (CTHRC1), serpin family E member 1 (SERPINE1), Versican (VCAN) was associated with tumor size, Uroplakin 1B (UPK1B) expression was associated with distant metastasis. Finally, multiple biological processes and signaling pathway associated with key genes revealed the underlying mechanism in GC.
Conclusions:
Taken together, CTHRC1, SERPINE1, VCAN, UPK1B were novel potential prognostic molecular markers for GC, which acted as oncogene to promote the development of GC.
Gastric carcinoma (GC) is one of the most common cancers with the fifth highest incidence of malignant tumors and the second highest death rate in the world. Ever-increasing investigations have shown that circular RNAs (circRNAs) are involved in the development of numerous cancers. But so far, the recognization for circMTO1 that is realized and studied as a cancer-suppressing gene is a small part and the regulatory mechanism of circMTO1 in GC has yet to be further explored. In this study, our experimental results delineated that circMTO1 exhibited much lower expression level in GC tissues and cells. CircMTO1 overexpression slowed down GC progression via inhibiting cell proliferation, migration, invasion and epithelial‐mesenchymal transition (EMT) process. Besides, circMTO1 acted as a sponge for miR‐3200-5p as well as it could negatively regulate the expression of miR‐3200-5p. Moreover, circMTO1 was verified to compete with PEBP1 to bind to miR‐3200-5p, thus decelerating the development of GC. In a word, this study was the first to indagate the underlying mechanism of circMTO1 in GC and confirmed circMTO1 exerted its anti-cancer effects by miR‐3200-5p/PEBP1 axis, implying that circMTO1 may become a new promising therapeutic target for GC patients.
The global cancer burden tends to increase. Tumors originating from the gastrointestinal (GI) tract such as the stomach and colorectum and liver are among the five most common cancers in both men and women worldwide. In women, colorectal cancer is the second most commonly diagnosed cancer followed by stomach cancer. However, colorectal cancer is the third most common malignancy in men followed by stomach and liver cancers. Gastrointestinal tumors, such as stomach and liver, are the most common causes of cancer death in men. In women, however, colorectal cancer is the third most common cancer-related death. The incidence of GI cancers shows significant geographical variation, with colorectal cancer incidence higher in Western Europe and North America, while gastric and liver cancer incidences are higher in Asia and Africa. Major risk factors for GI cancers include smoking, alcohol, infections, genetic factors, diet, and obesity. Contemporary changes in lifestyle and environmental factors as well as advances in medicine also affect epidemiology of GI cancers. Improved food preservation methods have been associated with reduced gastric cancer incidence, while the obesity epidemic in industrialized countries is associated with increased colon cancer incidence and high alcohol consumption with increased liver cancer rates. This chapter reviews our current knowledge on the changing epidemiology and risk factors of GI malignancies.
Objective: Gastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice.
Data Sources: The PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords “Helicobacter pylori,” “Pepsinogens,” and “Stomach Neoplasms.”
Study Selection: Original articles and reviews on the topics were selected.
Results: Anti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval.
Conclusions: The early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.
Background:
The clinicopathological significance of oncofetal mRNA-binding protein, human insulin-like growth factor II mRNA-binding protein 3 (IMP3), in gastric carcinoma (GC) is not fully understood.
Materials and methods:
Tissue microarray blocks with specimens from 346 patients with GC were constructed to evaluate the clinicopathological role of IMP3 expression in GC. These results were validated with an online dataset of 876 patients from the Kaplan-Meier Plotter. Sera from 15 controls and 57 patients with GC were collected in order to compare the levels of serum IMP3 between groups.
Results:
High expression of IMP3 was significantly associated with poor prognosis. Survival curves from the Kaplan-Meier Plotter showed that high IMP3 expression was significantly related to worse disease-free survival and overall survival.
Conclusion:
Tissue overexpression of IMP3 might be used as a predictor of advanced disease or lymph node metastasis, and is associated with poorer prognosis in GCs.
Background
Recent studies have demonstrated that acetyl-CoA synthetase 2 (ACSS2) plays a critical role in cancer cell survival; however, the role of ACSS2 in gastric carcinogenesis has not been determined.Methods
We investigated the expression of ACSS2 in human gastric cancer (GC) tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance.ResultsAmong 350 GCs, 219 cases (62.6%) were classified as ACSS2-low, whereas 131 cases (37.4%) were ACSS2-high. Loss of ACSS2 expression (ACSS2-low) was more frequently observed in undifferentiated histology (P = 0.002), in cases with MLH1-loss (P = 0.003), and in cases with SIRT3-low (P < 0.001). The ACSS2-low cases showed significantly lower mean disease-free survival (DFS, 68.5 vs. 81.8 months; P = 0.025) and overall survival (OS, 73.5 vs. 86.6 months; P = 0.029). In multivariate analysis, loss of ACSS2 expression was identified as one of the independent prognostic factors predicting worse DFS (HR: 1.547, P = 0.018) and OS (HR: 1.476, P = 0.036).Conclusions
We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC. J. Surg. Oncol. © 2015 Wiley Periodicals, Inc.
The overall prognosis of gastric cancer has gradually improved over the past decades with growing awareness of potential carcinogens, surveillance programs and early diagnosis, as well as advances in surgical techniques and multimodality treatments. Nevertheless, the outcome of advanced stage disease still remains poor with currently available treatments, and a worldwide consensus on the standard management thereof has not been established. To improve prognosis and quality of life in gastric cancer patients, both standardization and individualization of managements are imperative. Diagnostic tests and surgical procedures need to be further sophisticated and standardized based on more recent evidences from ongoing and future randomized controlled trials, while comprehensive management should be individualized to each patient. Future challenges lie with how to optimize personalized therapies by deciphering biological complexity of gastric cancer and incorporating molecular biomarkers in clinical practice to forecast prognosis and to guide targeted therapeutics in adjunct to current standards of care.
Gastric cancer is the second leading cause of oncologic death worldwide. One of the most noteworthy characteristics of this tumor's epidemiology is the marked decline reported in its incidence and mortality in almost every part of the globe in recent decades. This study sought to describe gastric cancer mortality time trends in Spain's regions for both sexes.
Mortality data for the period 1976 through 2005 were obtained from the Spanish National Statistics Institute. Cases were identified using the International Classification of Diseases 9th and 10th revision (codes 151 and C16, respectively). Crude and standardized mortality rates were calculated by geographic area, sex, and five-year period. Joinpoint regression analyses were performed to ascertain whether changes in gastric cancer mortality trends had occurred, and to estimate the annual percent change by sex and geographic area.
Gastric cancer mortality decreased across the study period, with the downward trend being most pronounced in women and in certain regions situated in the interior and north of mainland Spain. Across the study period, there was an overall decrease of 2.90% per annum among men and 3.65% per annum among women. Generally, regions in which the rate of decline was sharpest were those that had initially registered the highest rates. However, the rate of decline was not constant throughout the study period: joinpoint analysis detected a shift in trend for both sexes in the early 1980s.
Gastric cancer mortality displayed in both sexes a downward trend during the study period, both nationally and regionally. The different trend in rates in the respective geographic areas translated as greater regional homogeneity in gastric cancer mortality by the end of the study period. In contrast, rates in women fell more than did those in men. The increasing differences between the sexes could indicate that some risk factors may be modifying the sex-specific pattern of this tumor.
Using data from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results program, we analyzed stomach carcinoma incidence patterns by both histologic type and anatomic site.
We calculated age-adjusted (2000 U.S. standard) rates for 1978 to 2005, and for five time periods from 1978-1983 through 2001-2005 according to histologic type and anatomic site, separately and jointly. We also analyzed rates by race, gender, and age group.
During 1978 to 2005, more than 54,000 stomach carcinoma cases were diagnosed among residents of the nine Surveillance, Epidemiology, and End Results areas. Total stomach carcinoma rates declined by 34% from the 1978-1983 to the 2001-2005 time periods. By histologic type, intestinal rates decreased consistently, whereas those for diffuse rates increased through 2000 and declined in recent years. By anatomic site, cardia rates increased during earlier years and then decreased, whereas rates for all other sites declined. When considered jointly by histologic type and anatomic site, intestinal carcinoma rates decreased for all sites except the cardia; diffuse rates increased through 2000 and decreased in recent years for all sites except the overlapping/nonspecified sites. Both diffuse and intestinal rates were lowest among whites, intermediate among blacks, and highest among the other, primarily Asian, races, with only modest gender differences for the diffuse type. In contrast, cardia carcinoma rates were highest among whites and were notably higher among males, especially whites among whom the male/female rate ratio was five to one.
Stomach carcinoma incidence patterns differ by histologic type, anatomic site, race, gender, and age, suggesting that etiologic heterogeneity should be pursued in future research.
In many western countries an increase in incidence of adenocarcinoma of the oesophagus and/or gastric cardia have been reported. The aim of this study was to describe and compare trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in several areas of Europe, 1968-1995, using Eurocim (a database of cancer incidence and mortality data from 95 European cancer registries).
Time-trends in age-standardized incidence rates of adenocarcinomas of the oesophagus and gastric cardia are described in 11 population-based cancer registries from 10 countries in North, South, East, West and Central Europe, 1968-1995. The statistical significance of the time-trends in incidence was assessed using Poisson regression analysis.
An increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was observed in Northern Europe (Denmark), Southern Europe (Italy, Varese), Eastern Europe (Slovakia) and Western Europe (England and Wales, Scotland). In Central Europe (Switzerland, Basel) and in the cancer registries of Iceland (Northern Europe), France, Bas-Rhin and Calvados, Southern Ireland, and the Netherlands, Eindhoven (Western Europe) no rise in incidence was observed. The increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was accompanied by a decrease in incidence of both adenocarcinomas and non-adenocarcinomas of the non-cardia part of the stomach in almost all of the 11 cancer registries studied. Increased histological verification of tumours of the oesophagus and stomach and improvement in precision of histological diagnosis may partly explain the increase in incidence of adenocarcinomas in some registries.
This study, using Eurocim data, supports the findings from other time-trend studies of population-based cancer registries in western countries.
Since different histological types (HT) of gastric cancer (GC) may differ in their aetiology, time trend analysis by HT may afford an insight into aetiology. From the Gastric Cancer Registry of Japan, 161 067 cases diagnosed were retrieved between 1975 and 1989 to calculate the annual relative frequencies, stratified by age group and sex, of HT according to the Lauren and the Japanese Research Society for Gastric Cancer (JRSGC) classifications. Age- and sex-specific incidence rates by HT were estimated by multiplying the corresponding national cancer incidence rates of GC by the relative frequencies. Logistic regression models stratified by sex and age group were fitted to determine the time trends of HT. Using the Lauren classification, a decreasing trend of the intestinal type and a stable trend of the diffuse type were found. By the JRSGC classification, significant decreasing trends for most age groups were found for papillary and mucinous adenocarcinomas. Tubular adenocarcinomas (well differentiated type) showed a decreasing trend only in younger age groups. Tubular (moderately differentiated type), poorly differentiated adenocarcinomas, and signet ring cell carcinoma were statistically stable during the period. Considering changes in lifestyles of the Japanese, the result suggests that there are three aetiological types of GC.
To evaluate how often coding changes between and within revisions of the International Classification of Diseases (ICD) complicate the description of long-term trends in cause-specific mortality.
Data on cause-specific mortality between 1950 and 1999 for men and women aged 60 and older were obtained from Denmark, England and Wales, Finland, the Netherlands, Norway and Sweden. Data were obtained by five-year age groups. We constructed a concordance table using three-digit ICD codes. In addition we evaluated the occurrence of mortality discontinuities by visually inspecting cause-specific trends and country-specific background information. Evaluation was also based on quantification of the discontinuities using a Poisson regression model (including period splines). We compared the observed trends in cause-specific mortality with the trends after adjustment for the discontinuities caused by changes to coding.
In 45 out of 416 (10.8 %) instances of ICD revisions to cause-specific mortality codes, significant discontinuities that were regarded as being due to ICD revisions remained. The revisions from ICD-6 and ICD-7 to ICD-8 and a wide range of causes of death, with the exception of the specific cancers, were especially affected. Incidental changes in coding rules were also important causes of discontinuities in trends in cause-specific mortality, especially in England and Wales, Finland and Sweden. Adjusting for these discontinuities can lead to significant changes in trends, although these primarily affect only limited periods of time.
Despite using a carefully constructed concordance table based on three-digit ICD codes, mortality discontinuities arising as a result of coding changes (both between and within revisions) can lead to substantial changes in long-term trends in cause-specific mortality. Coding changes should therefore be evaluated by researchers and, where necessary, controlled for.
Registration of births, recording deaths by age, sex and cause, and calculating mortality levels and differentials are fundamental to evidence-based health policy, monitoring and evaluation. Yet few of the countries with the greatest need for these data have functioning systems to produce them despite legislation providing for the establishment and maintenance of vital registration. Sample vital registration (SVR), when applied in conjunction with validated verbal autopsy procedures and implemented in a nationally representative sample of population clusters represents an affordable, cost-effective, and sustainable short- and medium-term solution to this problem. SVR complements other information sources by producing age-, sex-, and cause-specific mortality data that are more complete and continuous than those currently available. The tools and methods employed in an SVR system, however, are imperfect and require rigorous validation and continuous quality assurance; sampling strategies for SVR are also still evolving. Nonetheless, interest in establishing SVR is rapidly growing in Africa and Asia. Better systems for reporting and recording data on vital events will be sustainable only if developed hand-in-hand with existing health information strategies at the national and district levels; governance structures; and agendas for social research and development monitoring. If the global community wishes to have mortality measurements 5 or 10 years hence, the foundation stones of SVR must be laid today.
A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries waiting to be "translated" into useful therapies and diagnostics. In addition to highlighting the major research advances over the past year, this report also identifies key barriers to accelerating the pace of cancer research and outlines ASCO's recommendations for overcoming them. Despite these and other challenges, there is much good news on the front lines of cancer research. This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States.
Geographical variation and temporal trends in the incidence of esophageal and gastric cancers vary according to both tumour morphology and organ subsite. Both diseases are among the deadliest forms of cancer. The incidence and survival rates for gastric and esophageal carcinoma in British Columbia (BC) between 1990 and 1999 are described.
Incidence data for the period 1990 to 1999 were obtained from the BC Cancer Registry. Age-adjusted incidence and survival rates were computed by anatomical subsite, histological type and sex. All rates were standardized to the 1996 Canadian population. The estimated annual percentage change (EAPC) was used to measure incidence changes over time. Kaplan-Meier curves were used to show survival rates, and log-rank tests were used to test for differences in the curves among various groups.
Between 1990 and 1999, 1741 esophageal cancer cases and 3431 gastric cancer cases were registered in BC. There was an increase in the incidence of adenocarcinoma of the esophagus over time (EAPC=9.6%) among men, and of gastric cardia cancer among both women (EAPC=9.2%) and men (EAPC=3.8%). Patients with proximal gastric (cardia) cancer had significantly better survival rates than patients with cancer in the lower one-third of the esophagus. Among gastric cancers, patients with distal tumours had a significantly better survival rate than patients with proximal tumours.
The incidences of proximal gastric cancer and esophageal adenocarcinoma are increasing, and their survival patterns are different. Examining these cancers together may elucidate new etiological and prognostic factors.
Gastric cancer is the leading cause of death from cancer in Japan. In 2004, there were 50 562 deaths from gastric cancer; they accounted for 15.8% of the total number of cancer deaths. Since 1983, under the Health Service Law for the Aged, gastric cancer screening has been conducted nationwide for all residents aged 40 years and over.
On the basis of the standardized method developed for the Japanese Guidelines for Cancer Screening, the efficacies of various methods for gastric cancer screening were evaluated and the guideline was developed.
Four methods for gastric cancer screening were evaluated: photofluorography, endoscopy, serum pepsinogen testing and Helicobacter pylori antibody testing. On the basis of the analytic framework involving key questions, 1715 articles, published from January 1985 to February 2005, were selected using MEDLINE, the Japanese Medical Research Database and other methods. After the systematic literature review, 10 articles were identified as direct evidence and 49 articles as indirect evidence. The studies that evaluated mortality reduction from gastric cancer included five case-control and two cohort studies for radiographic screening. On the basis of the balance of benefits and harms, the recommendations for population-based and opportunistic screening were formulated. Gastric cancer screening using photofluorography was recommended for both screening programs. The other methods were not recommended for population-based screening due to insufficient evidence.
The guideline for gastric cancer screening guideline was developed based on the previously established method. Gastric cancer screening using photofluorography is recommended for population-based and opportunistic screening in Japan.
: We analysed data from 49 cancer registries in 18 European countries over the period 1988-1999 to delineate time trends in cancer survival. Survival increased in Europe over the study period for all cancer sites that were considered. There were major survival increases in 5 year age-adjusted relative survival for prostate (from 58% to 79%), colon and rectum (from 48% to 54% men and women), and breast (from 74% to 83%). Improvements were also significant for stomach (from 22% to 24%), male larynx (from 62% to 64%), skin melanoma (from 78% to 83%), Hodgkin disease (from 77% to 83%), non-Hodgkin lymphoma (from 49% to 56%), leukaemias (from 37% to 42%), and for all cancers combined (from 34% to 39% in men, and from 52% to 59% in women). Survival did not change significantly for female larynx, lung, cervix or ovary. The largest increases in survival typically occurred in countries with the lowest survival, and contributed to the overall reduction of survival disparities across Europe over the study period. Differences in the extent of PSA testing and mammographic screening, and increasing use of colonoscopy and faecal blood testing together with improving cancer care are probably the major underlying reasons for the improvements in survival for cancers of prostate, breast, colon and rectum. The marked survival improvements in countries with poor survival may indicate that these countries have made efforts to adopt the new diagnostic procedures and the standardised therapeutic protocols in use in more affluent countries.
Cluster analysis is the automated search for groups of related observations in a dataset. Most clustering done in practice is based largely on heuristic but intuitively reasonable procedures, and most clustering methods available in commercial software are also of this type. However, there is little systematic guidance associated with these methods for solving important practical questions that arise in cluster analysis, such as how many clusters are there, which clustering method should be used, and how should outliers be handled. We review a general methodology for model-based clustering that provides a principled statistical approach to these issues. We also show that this can be useful for other problems in multivariate analysis, such as discriminant analysis and multivariate density estimation. We give examples from medical diagnosis, minefield detection, cluster recovery from noisy data, and spatial density estimation. Finally, we mention limitations of the methodology and discuss recent developments in model-based clustering for non-Gaussian data, high-dimensional datasets, large datasets, and Bayesian estimation.
The international decline in gastric cancer is mainly attributed to improved socio-economic conditions. However, some southern and eastern European countries showed slower and later decline, reflecting a less favourable general environment. The same probably applies to regional differences within countries, making national indicators potentially misleading. Fitting log-linear Poisson models we compared trends in gastric cancer mortality (1984–1999) across 18 Portuguese regions. Pearson correlation coefficients were computed to assess the regional association between decline in cancer mortality and baseline cancer mortality and variation in indices of social development and medical care. National gastric cancer mortality changed −2.0%/year in men and −2.2%/year in women. The regional yearly variation in mortality ranged from −3.5% [95% confidence interval (CI) −4.5 to −2.5] to −0.6% (95% CI −1.4 to 0.2) in men, and from −3.7% (95% CI −4.8 to −2.7) to −0.8% (95% CI −1.6 to 0.0) in women. Regional variation was not significantly associated with baseline gastric cancer mortality (r=0.18, P=0.47), but with the variation in post-neonatal mortality (r=0.59, P=0.01). In Portugal, gastric cancer shows a wide regional variation in frequency trends. The correlation with known indicators of social and economic development indicates that future improvement in gastric cancer rates is expected in parallel with a more widespread development.
A training set of data has been used to construct a rule for predicting future responses. What is the error rate of this rule? This is an important question both for comparing models and for assessing a final selected model. The traditional answer to this question is given by cross-validation. The cross-validation estimate of prediction error is nearly unbiased but can be highly variable. Here we discuss bootstrap estimates of prediction errors, which can be thought of as smoothed versions of cross-validation. We show that a particular bootstrap method, the ·632+ rule, substantially outperforms cross-validation in a catalog of 24 simulation experiments. Besides providing point estimates, we also consider estimating the variability of an error rate estimate. All of the results here are nonparametric and apply to any possible prediction rule; however, we study only classification problems with 0-1 loss in detail. Our simulations include “smooth” prediction rules like Fisher’s linear discriminant function and unsmooth ones like nearest neighbors.
Cancer is set to become a major cause of morbidity and mortality in the coming decades in every region of the world. We aimed to assess the changing patterns of cancer according to varying levels of human development.
We used four levels (low, medium, high, and very high) of the Human Development Index (HDI), a composite indicator of life expectancy, education, and gross domestic product per head, to highlight cancer-specific patterns in 2008 (on the basis of GLOBOCAN estimates) and trends 1988-2002 (on the basis of the series in Cancer Incidence in Five Continents), and to produce future burden scenario for 2030 according to projected demographic changes alone and trends-based changes for selected cancer sites.
In the highest HDI regions in 2008, cancers of the female breast, lung, colorectum, and prostate accounted for half the overall cancer burden, whereas in medium HDI regions, cancers of the oesophagus, stomach, and liver were also common, and together these seven cancers comprised 62% of the total cancer burden in medium to very high HDI areas. In low HDI regions, cervical cancer was more common than both breast cancer and liver cancer. Nine different cancers were the most commonly diagnosed in men across 184 countries, with cancers of the prostate, lung, and liver being the most common. Breast and cervical cancers were the most common in women. In medium HDI and high HDI settings, decreases in cervical and stomach cancer incidence seem to be offset by increases in the incidence of cancers of the female breast, prostate, and colorectum. If the cancer-specific and sex-specific trends estimated in this study continue, we predict an increase in the incidence of all-cancer cases from 12·7 million new cases in 2008 to 22·2 million by 2030.
Our findings suggest that rapid societal and economic transition in many countries means that any reductions in infection-related cancers are offset by an increasing number of new cases that are more associated with reproductive, dietary, and hormonal factors. Targeted interventions can lead to a decrease in the projected increases in cancer burden through effective primary prevention strategies, alongside the implementation of vaccination, early detection, and effective treatment programmes.
None.
We sought to assess the current status of global data on death registration and to examine several indicators of data completeness and quality.
We summarized the availability of death registration data by year and country. Indicators of data quality were assessed for each country and included the timeliness, completeness and coverage of registration and the proportion of deaths assigned to ill-defined causes.
At the end of 2003 data on death registration were available from 115 countries, although they were essentially complete for only 64 countries. Coverage of death registration varies from close to 100% in the WHO European Region to less than 10% in the African Region. Only 23 countries have data that are more than 90% complete, where ill-defined causes account for less than 10% of total of causes of death, and where ICD-9 or ICD-10 codes are used. There are 28 countries where less than 70% of the data are complete or where ill-defined codes are assigned to more than 20% of deaths. Twelve high-income countries in western Europe are included among the 55 countries with intermediate-quality data.
Few countries have good-quality data on mortality that can be used to adequately support policy development and implementation. There is an urgent need for countries to implement death registration systems, even if only through sample registration, or enhance their existing systems in order to rapidly improve knowledge about the most basic of health statistics: who dies from what?
Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.
Linear Mixed-Effects * Theory and Computational Methods for LME Models * Structure of Grouped Data * Fitting LME Models * Extending the Basic LME Model * Nonlinear Mixed-Effects * Theory and Computational Methods for NLME Models * Fitting NLME Models
Gastric cancer is prevalent globally, particularly in Asian countries such as Japan and Korea. While the prevalence of gastric cancer is not nearly as high in the United States (U.S.) as in Asia, the treatment armamentarium differs widely between regions. The role of surgery for gastric cancer in the U.S. has changed drastically over the last decade. While the natural history of gastric cancer seen in the U.S. markedly differs from that seen in Asia, the U.S. experience with endoscopic and minimally invasive techniques is beginning to parallel those seen in Japan and Korea. Minimally invasive surgery has truly come into the forefront of our surgical armamentarium, and its role, along with robotic and endoscopic approaches, remains to be defined as standard of care. At present, minimally invasive approaches appear to offer oncologically equivalent outcomes compared with standard open gastrectomy when performed by experienced surgeons. Extended lymphadenectomy does not appear to offer benefit with improved survival in our patient population, although sufficient lymph node sampling is imperative for adequate staging. Despite aggressive approaches to surgical resection for cure, the U.S. population tends to present with more advanced disease and have a worse prognosis than our Asian counterparts. Palliation with resection and possibly stent placement should be offered for improved quality of life in late-stage disease.
To analyze the components of the favorable trends in gastric cancer in Europe.
From official certified deaths from gastric cancer and population estimates for 42 countries of the European geographical region, during the period 1950 to 2007, age-standardized death rates (World Standard Population) were computed, and an age-period-cohort analysis was performed.
Central and Northern countries with lower rates in the 2005 to 2007 period, such as France (5.28 and 1.93/100,000, men and women respectively) and Sweden (4.49 and 2.21/100,000), had descending period and cohort effects that decreased steeply from the earliest cohorts until those born in the 1940s, to then stabilize. Former nonmarket economy countries had mortality rates greater than 20/100,000 men and 10/100,000 women, and displayed a later start in the cohort effect fall, which continued in the younger cohorts. Mortality remained high in some countries of Southern and Eastern Europe.
The decrease in gastric cancer mortality was observed in both cohort and period effects but was larger in the cohorts, suggesting that the downward trends are likely to persist in countries with higher rates. In a few Western countries with very low rates an asymptote appears to have been reached for cohorts born after the 1940s, particularly in women.
The purpose of the present study was to collect data from population-based cancer registries and to calculate relative 5-year survival of cancer patients in Japan. We also sought to determine time trends and to compare the results with international studies.
We asked 11 population-based cancer registries to submit individual data for patients diagnosed from 1993 to 1999, together with data on outcome after 5 years. Although all these registries submitted data (491 772 cases), only six met the required standards for the quality of registration data and follow-up investigation. The relative 5-year survival calculated by pooling data from 151 061 cases from six registries was taken as the survival for cancer patients in Japan.
Relative 5-year survival (1997-99) was 54.3% for all cancers (males: 50.0%, females: 59.8%). Survival figures for all sites changed slightly over the 7-year period, from 53.2% for the first 4 years of the study (1993-96) to 54.3% for the last 3 years (1997-99), however, a major improvement was observed in several primary sites. Some overall survival was lower in Japan than in the USA, but similar to that in European countries. Specifically, survival for uterine cancer, prostate cancer, testis cancer, lymphoma and leukemia was much lower in Japan than in other countries. However, survival was better in Japan mainly for cancers of the esophagus, stomach, colon, liver and gallbladder.
The study suggests an improvement in cancer survival in several primary sites in Japan, which is consistent with the development of treatments and early detection.
Survival of gastric cancer in the Western world remains poor. We conducted a retrospective population-based study to evaluate trends in incidence, treatment and outcome of gastric adenocarcinoma.
All patients diagnosed with gastric adenocarcinoma during 1990-2007 in the Dutch Eindhoven Cancer Registry area were included (n=4,797). Trend analyses were conducted for incidence, mortality, tumour and patient characteristics, treatment and crude overall survival, according to tumour location (cardia versus non-cardia). Temporal changes in the odds of undergoing surgery and the risk of death were analysed by means of multivariable regression methods.
Age-standardised incidence decreased among males (24-12 per 100,000 inhabitants) and females (10-6); mortality rates decreased at a similar pace. The proportion of cardia tumours remained stable. Stage distribution worsened over time among patients with cardia (stages I and II: 32% in 1990-1993 and 22% in 2006-2007, p=0.005) and non-cardia (stage IV: 33% in 1990-1993 and 40% in 2006-2007, p=0.0003) cancer. Chemotherapy rates increased in all settings. Five-year survival worsened over time for patients with non-cardia tumours. Age and stage had significant influence on survival after stratification for tumour localisation. After adjustments for relevant factors (i.e. stage), the risk of death decreased since the late 90s for patients with a cardia tumour (hazard ratio 0.8, p=0.01).
The absence of improvement in survival rates indicates the need for earlier detection and prospective studies to evaluate new therapy regimens with standardised surgery and pathology.
The problem of selecting one of a number of models of different dimensions is treated by finding its Bayes solution, and evaluating the leading terms of its asymptotic expansion. These terms are a valid large-sample criterion beyond the Bayesian context, since they do not depend on the a priori distribution.
Until the mid-1990s, gastric cancer has been the first cause of cancer death worldwide, although rates had been declining for several decades and gastric cancer has become a relatively rare cancer in North America and in most Northern and Western Europe, but not in Eastern Europe, Russia and selected areas of Central and South America or East Asia. We analyzed gastric cancer mortality in Europe and other areas of the world from 1980 to 2005 using joinpoint regression analysis, and provided updated site-specific incidence rates from 51 selected registries. Over the last decade, the annual percent change (APC) in mortality rate was around -3, -4% for the major European countries. The APC were similar for the Republic of Korea (APC = -4.3%), Australia (-3.7%), the USA (-3.6%), Japan (-3.5%), Ukraine (-3%) and the Russian Federation (-2.8%). In Latin America, the decline was less marked, but constant with APC around -1.6% in Chile and Brazil, -2.3% in Argentina and Mexico and -2.6% in Colombia. Cancers in the fundus and pylorus are more common in high incidence and mortality areas and have been declining more than cardia gastric cancer. Steady downward trends persist in gastric cancer mortality worldwide even in middle aged population, and hence further appreciable declines are likely in the near future.
Normal mixture models are widely used for statistical modeling of data, including cluster analysis.
However maximum likelihood estimation (MLE) for normal mixtures using the EM algorithm may fail as the result of singularities or degeneracies. To avoid this, we propose replacing the MLE by a maximum a posteriori (MAP) estimator, also found by the EM algorithm. For choosing the number of components and the model parameterization, we propose a modified version of BIC, where the likelihood is evaluated at the MAP instead of the MLE. We use a highly dispersed proper conjugate prior, containing a small fraction of one observation's worth of information. The resulting method avoids degeneracies and singularities, but when these are not present it gives similar results to the standard method using MLE, EM and BIC.
We analysed data from 49 cancer registries in 18 European countries over the period 1988-1999 to delineate time trends in cancer survival. Survival increased in Europe over the study period for all cancer sites that were considered. There were major survival increases in 5 year age-adjusted relative survival for prostate (from 58% to 79%), colon and rectum (from 48% to 54% men and women), and breast (from 74% to 83%). Improvements were also significant for stomach (from 22% to 24%), male larynx (from 62% to 64%), skin melanoma (from 78% to 83%), Hodgkin disease (from 77% to 83%), non-Hodgkin lymphoma (from 49% to 56%), leukaemias (from 37% to 42%), and for all cancers combined (from 34% to 39% in men, and from 52% to 59% in women). Survival did not change significantly for female larynx, lung, cervix or ovary. The largest increases in survival typically occurred in countries with the lowest survival, and contributed to the overall reduction of survival disparities across Europe over the study period. Differences in the extent of PSA testing and mammographic screening, and increasing use of colonoscopy and faecal blood testing together with improving cancer care are probably the major underlying reasons for the improvements in survival for cancers of prostate, breast, colon and rectum. The marked survival improvements in countries with poor survival may indicate that these countries have made efforts to adopt the new diagnostic procedures and the standardised therapeutic protocols in use in more affluent countries.
Although considerable resources are being allocated globally to cancer research, efforts to implement these findings efficiently are lagging behind. Enough is known about the cause of common tumors such as lung, oral, and liver cancer to allow active measures to be taken for their prevention. Effective early detection programs have been developed for cervical, breast, and oral cancer, and treatment methods exist whereby at least one-third of all cancer patients can be cured if their disease is detected early. Unfortunately, however, most cancer activities currently in place were developed haphazardly and lack overall coordination. National cancer control efforts can be more effectively planned and implemented if they follow a systematic stepwise approach of assessing the current situation, setting health objectives, evaluating the possible strategies, and setting priorities using quantitative assessments. Cancer affects both developed and developing countries of the world, and well planned national efforts emphasizing prevention and early detection can significantly reduce the cancer problem.
Background:
Annually, there are more than 6 million deaths from a type of malignant neoplasia worldwide. In developing countries, the highest rates of incidence of malignant neoplasias are uterine cervical cancer, stomach, lung, esophagus, pharynx, and liver cancers. Recent estimates on the incidence of cancer worldwide show that, in 1990, stomach cancer (SC) was the second most frequent type of cancer (900,000 new cases annually). Rates of incidence have decreased consistently in nearly all areas of the world. In Mexico, however, rates of incidence and mortality have increased gradually between 1980 and 1997; in 1995, 4,685 people died of SC in Mexico. This report presents a descriptive analysis of SC mortality in Mexico.
Methods:
A mortality database edited from the electronic files of the National Institute of Informatics, Statistics and Geography (INEGI) in Mexico was used; population denominators were edited by the Mexican National Population Council (Conapo). Adjusted mortality rates, taking as standard of reference the population of Mexico City by sex, year, and 10-year age groups were calculated as well as the sex ratio for the 1980-1997 period. To evaluate the magnitude of risks by state, the standardized mortality ratio (SMR) was calculated; prematurity was evaluated through the potential lost-life years index (PLLYI). The analysis was carried out using the Excel and Stata 5.0 software programs.
Results:
During the years from 1980 to 1997, in Mexico the total number of deaths from SC was 76,315. The male:female ratio was 1.2:1.0. SMR by state showed that the states of Yucatán, Sonora, Zacatecas, Michoacán, and Chiapas had higher mortality rates. The PLLYI was higher for males in the states of Chiapas, Sonora, Chihuahua, Zacatecas, and Southern Baja California, and higher for females in Chiapas, Oaxaca, Yucatán, Puebla, and Campeche.
Conclusions:
World statistics on mortality caused by SC suggest a decreasing trend. Findings for this study show an increase in the adjusted mortality rates by SC during the 1980-1997 period in Mexico. However, when analyzing the different indicators that reveal risks, magnitude, and prematurity of mortality, there is a differential trend in mortality by sex that includes regional patterns probably related to different socioeconomic levels.
The actual distribution of Helicobacter pylori infection and its related diseases in various Asian countries is controversial. Only limited information is available regarding this issue. We discuss the etiological role of H. pylori in gastric cancer through the Asian experience. Seroprevalence of H. pylori infection in asymptomatic subjects and the annual incidence rate of gastric cancer per 100,000 in various Asian countries are summarized from literature reviews and World Health Organization statistics, respectively. There is a large intercountry variation in incidence of gastric cancer and H. pylori seroprevalence among Asian countries. There is a strong link between H. pylori infection and gastric cancer in many countries, such as Japan. By contrast, the prevalence of H. pylori infection is high in some countries, including India and Bangladesh, but low gastric cancer rates have been reported. These disparate observations represent the Asian enigma. Factors that may influence the etiology of gastric cancer include the genetic diversity of the infecting H. pylori strains and differences in the host genetic background in various ethnic groups, including gastric acid secretion and genetic polymorphisms in proinflammatory cytokines. These factors, in addition to environmental factors, such as personal hygiene and dietary habits, reflect the multifactorial etiology of gastric cancer.
The international decline in gastric cancer is mainly attributed to improved socio-economic conditions. However, some southern and eastern European countries showed slower and later decline, reflecting a less favourable general environment The same probably applies to regional differences within countries, making national indicators potentially misleading. Fitting log-linear Poisson models we compared trends in gastric cancer mortality (1984-1999) across 18 Portuguese regions. Pearson correlation coefficients were computed to assess the regional association between decline in cancer mortality and baseline cancer mortality and variation in indices of social development and medical care. National gastric cancer mortality changed -2.0% year in men and -2.2% year in women. The regional yearly variation in mortality ranged from -3.5% [95% confidence interval (CI) -4.5 to -2.5] to -0.6% (95% CI -1.4 to 0.2) in men, and from -3.7% (95% CI -4.8 to -2.7) to -0.8% (95% CI -1.6 to 0.0) in women. Regional variation was not significantly associated with baseline gastric cancer mortality (r = 0.18, P = 0.47), but with the variation in post-neonatal mortality (r = 0.59, P = 0.01). In Portugal, gastric cancer shows a wide regional variation in frequency trends. The correlation with known indicators of social and economic development indicates that future improvement in gastric cancer rates is expected in parallel with a more widespread development.
Population endoscopic screening for gastric cancer is generally deemed not to be cost-effective except in Japan, where its prevalence is very high. However, in the absence of screening, patients present with advanced disease, and prognosis is poor. We conducted a cost utility analysis to determine whether endoscopic screening for stomach cancer in intermediate-risk population would be cost-effective and to better define the high-risk groups in the population who would benefit from such strategy.
Cost-effectiveness analysis was performed by using a Markov Model. Simulation was performed on Singapore (intermediate-risk) population and various high-risk subgroups. Comparison was made between 2-yearly endoscopic mass screening program versus no screening. Data sources were extracted from relevant studies published from 1980-2004 identified via systematic PUBMED search. Main outcome measures were deaths caused by stomach cancer averted, cost per life saved, and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life year (QALY) saved.
Screening of high-risk group of Chinese men (age-standardized rate, 25.9/100,000) from 50-70 years old is highly cost-effective, with cost benefit of United States $26,836 per QALY. Screening this cohort of 199,000 subjects prevents 743 stomach cancer deaths and saves 8234 absolute life years. Cost of averting 1 cancer death is United States $247,600. Cost-effectiveness was most sensitive to incidence of stomach cancer and cost of screening endoscopy.
Screening of stomach cancer in moderate to high-risk population subgroups is cost-effective. Targeted screening strategies for stomach cancer should be explored.
Noncardia gastric adenocarcinoma is not frequently mentioned in the United States. However, it is unclear if the previously reported decline in noncardia gastric adenocarcinoma has continued, and if detection and management has affected overall survival outside the setting of clinical trials.
We used the Surveillance, Epidemiology, and End Results registry (SEER) to identify all cases of noncardia gastric adenocarcinoma diagnosed between 1973 and 2002. The yearly age-adjusted incidence rates and the relative survival rates were calculated. Cox proportional hazards (PH) models were used to examine temporal trends from 1983 to 2003.
Between 1973 and 2002, there were 24,103 cases of noncardia gastric adenocarcinoma. The age-adjusted yearly incidence rate declined by 23% between 1973 and 2002 from 4.3 to 3.3 per 100,000 person-years. However, the incidence of localized noncardia gastric adenocarcinoma (invasive neoplasm confined to the organ of origin) remained without change between 0.9 and 1.0 per 100,000 person-years, and increased with age, especially in the 85+ yr age group (a 47% increase between 1973 and 2002). The incidence rates in men were double those in women, and 1.6-fold and 2.6-fold higher in blacks and other races (mostly Asians), respectively, compared with whites. Patients with radiation and chemotherapy after gastrectomy had a 22% better mortality risk compared with those treated with gastrectomy alone. The Cox PH analysis shows no significant change in mortality risk related to year of diagnosis between 1983 and 2002, both in unadjusted as well as adjusted analyses. However, there were significant independent regional and racial variations in survival. Asians had a 17% lower mortality risk compared with whites.
Despite the overall decline in noncardia gastric adenocarcinoma, the incidence of local stage disease has remained stable in most ages and even increased in old ages. Unfortunately, there has been no significant improvement in survival during the past 20 yr. Moreover, there remain considerable regional as well as racial variations in mortality.
At an individual level Helicobacter pylori was associated with the occurrence of gastric cancer but in some African and Asian countries its prevalence runs with low gastric cancer rates, the so-called African and Asian enigmas. We assessed whether the association between gastric cancer and H. pylori prevalence at an area level is modified by the level of exposure to fruits and vegetables, alcohol or tobacco. Regression models were fitted to data from 58 countries using as dependent variable log transformed gastric cancer rates and as independent covariables the H. pylori prevalence, fruits and vegetables consumption, cigarette smoking, alcohol intake and interaction terms. The levels of alcohol consumption or cigarette smoking modified the association between gastric cancer and H. pylori infection. Models including H. pylori prevalence, alcohol consumption, cigarette smoking and the interaction terms H. pylori x alcohol or H. pylori x tobacco were used to compute gastric cancer incidence multiplying regression coefficients by a H. pylori prevalence of 85% (the approximate median in African countries) and the median figures observed in each continent for alcohol and tobacco availability. The expected gastric cancer incidence per 100,000 would be 5.7 assuming the alcohol and tobacco availability in African countries, 7.0 in Asia and Oceania, 16.0 in America and 26.0 in Europe. The interaction between H. pylori and cigarette or alcohol consumption may contribute to further explain the international variation in gastric cancer and the so-called African and Asian enigmas.
Stomach cancer still remains one of the most frequent tumors in Italy and Europe. The aim of this paper is to present estimates for stomach cancer mortality, incidence and prevalence over the period 1970-2010 for the Italian regions and for Italy as a whole.
Estimated figures for incidence, prevalence and mortality were obtained by using the MIAMOD method. Starting from the knowledge of mortality in the period 1970-1999 and of relative survival in the period of diagnosis 1978-1994, we derived incidence and prevalence estimates and projections up to the year 2010 by means of a statistical back-calculation approach. Survival at the regional and national levels was modelled on the basis of published survival data from the Italian cancer registries.
Incidence and mortality trends for both sexes decrease by about 60% during the estimation period 1970-2010. Both indicators show a 2-fold male/female ratio all over the country, and a similar gender time trend. The incidence and mortality in the North and Center of the country are estimated to be higher and to decrease more steeply than those in the South, both for men and women. A total of around 13,000 incident cases, 57,000 prevalent cases, and 8,000 deaths are estimated to have occurred in Italy in 2005.
The incidence and mortality trends are estimated to decline during the entire period 1970-2010, with different slopes between northern-central and southern regions. The incidence and mortality are quite similar among Italian regions, showing that the risk of developing the disease diminishes and is becoming more homogeneous than in the past decades all over the country.
This paper presents comparable tobacco use prevalence estimates for the WHO European region for two common definitions of tobacco use: current smoker (occasional and daily) and daily smoker. Data collections held in the WHO Global InfoBase (www.who.int/infobase) were used to examine patterns of tobacco use at the country level, in the region as a whole and for specific subregional groups. Data from 275 sources presenting tobacco use prevalence by age and sex and representing 46 out of 52 countries in the WHO European region met the inclusion criteria. Regression models were used to adjust country-reported prevalence to a standard set of definitions and age groups. Estimates were projected to a set of standard reporting years, 2002, 2005 and 2015. The prevalence of current smoking and daily smoking was 33.2 and 28.4%, respectively in 2002. Male smokers had overall higher prevalence of daily smoking, 37.7% and current smoking, 43.1% in 2002. The corresponding rates for female smokers were 19.3% for daily smokers and 23.4% for current smokers in 2002. The overall prevalence declines slightly by 2015 for male daily smokers to 33.5% but increases for female daily smokers to 20.1%. The increase in female smokers is most apparent in the eastern, southern and western parts of Europe.