Divergent trends for gastric cancer incidence by anatomical subsite in US adults

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.
Gut (Impact Factor: 14.66). 05/2011; 60(12):1644-9. DOI: 10.1136/gut.2010.236737
Source: PubMed

ABSTRACT Age-specific analyses of non-cardia gastric cancer incidence reveal divergent trends among US whites: rates are declining in individuals aged 40 years and older but rising in younger persons. To investigate this heterogeneity further, incidence trends were evaluated by anatomical subsite.
Gastric cancer incidence data for 1976-2007 were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the US Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change were calculated by age group (25-39, 40-59 and 60-84 years), race/ethnicity and subsite.
Based on data from the nine oldest SEER registries (covering ~10% of the US population), rates for all non-cardia subsites decreased in whites and blacks, except for corpus cancer, which increased between 1976 and 2007 with estimated annual percentage changes of 1.0% (95% CI 0.1% to 1.9%) for whites and 3.5% (95% CI 1.8% to 5.2%) for blacks. In contrast, rates for all non-cardia subsites including corpus cancer declined among other races. In combined data from NPCR and SEER registries (covering 89% of the US population), corpus cancer significantly increased between 1999 and 2007 among younger and middle-aged whites; in ethnic-specific analyses, rates significantly increased among the same age groups in non-Hispanic whites and were stable among Hispanic whites. Age-specific rates for all subsites declined or were stable in this period among blacks and other races.
Long- and short-term incidence trends for gastric cancers indicate a shifting distribution by anatomical subsite. Corpus cancer may have distinctive aetiology and changing risk factor exposures, warranting further investigation.

Download full-text


Available from: M. Constanza Camargo, Apr 04, 2014
20 Reads
  • Source
    • "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]. The validity of data on gastric cancer subtypes is, however, open to discussion [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer incidence and mortality decreased substantially over the last decades in most countries worldwide, with differences in the trends and distribution of the main topographies across regions. To monitor recent mortality trends (1980–2011) and to compute short-term predictions (2015) of gastric cancer mortality in selected countries worldwide, we analysed mortality data provided by the World Health Organization. We also analysed incidence of cardia and non-cardia cancers using data from Cancer Incidence in Five Continents (2003–2007). The joinpoint regression over the most recent calendar periods gave estimated annual percent changes (EAPC) around −3% for the European Union (EU) and major European countries, as well as in Japan and Korea, and around −2% in North America and major Latin American countries. In the United States of America (USA), EU and other major countries worldwide, the EAPC, however, were lower than in previous years. The predictions for 2015 show that a levelling off of rates is expected in the USA and a few other countries. The relative contribution of cardia and non-cardia gastric cancers to the overall number of cases varies widely, with a generally higher proportion of cardia cancers in countries with lower gastric cancer incidence and mortality rates (e.g. the USA, Canada and Denmark). Despite the favourable mortality trends worldwide, in some countries the declines are becoming less marked. There still is the need to control Helicobacter pylori infection and other risk factors, as well as to improve diagnosis and management, to further reduce the burden of gastric cancer.
    European journal of cancer (Oxford, England: 1990) 05/2014; 50(7). DOI:10.1016/j.ejca.2014.01.029 · 5.42 Impact Factor
  • Source
    • "Camargo et al., reported that cancers in the distal stomach (antrum) have decreased, while more proximal gastric cancers in the corpus and cardia have increased [95]. Extrapolating from these epidemiologic trends, adenocarcinomas of the stomach appear to exhibit a different behavior depending on their location suggesting that different molecular mechanisms regulate neoplastic transformation in the proximal and distal gastric sub-sites [95] [96]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This review summarizes emerging information regarding the Hedgehog (Hh) signaling pathway during neoplastic transformation in the gastrointestinal tract. Although there is a role for the well-established canonical pathway in which Hedgehog ligands interact with their receptor Patched, there is sufficient evidence that downstream components of the Hh pathway, e.g., Gli1, are hijacked by non-Hh signaling pathways to promote the conversion of the epithelium to dysplasia and carcinoma. We review the canonical pathway and involvement of primary cilia, and then focus on current evidence for Hh signaling in luminal bowel cancers as well as accessory organs, i.e., liver, pancreas and biliary ducts. We conclude that targeting the Hh pathway with small molecules, nutriceuticals and other mechanisms will likely require a combination of inhibitors that target Gli transcription factors in addition to canonical modulators such as Smoothened.
    Cancer Treatment Reviews 08/2013; 40(1). DOI:10.1016/j.ctrv.2013.08.003 · 7.59 Impact Factor
  • Source
    • "Gastric cancer is among the more prevalent cancers worldwide, with a survival rate of 27% [13]. Interestingly, a shift in the most frequent site of gastric cancer from the distal stomach (antrum) to the more proximal corpus and cardia has been observed over the past 10 years, possibly reflecting differences in cancer etiology and risk factors for these two regions of the stomach [14]. Mouse models of gastric tumorigenesis frequently exhibit changes in the gastric corpus/fundus with little or no changes in the antrum. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation in the stomach can lead to gastric cancer. We previously reported that gastrin-deficient (Gast(-/-)) mice develop bacterial overgrowth, inflammatory infiltrate, increased Il-1β expression, antral hyperplasia and eventually antral tumors. Since Hedgehog (Hh) signaling is active in gastric cancers but its role in precursor lesions is poorly understood, we examined the role of inflammation and Hh signaling in antral hyperplasia. LacZ reporter mice for Sonic hedgehog (Shh), Gli1, and Gli2 expression bred onto the Gast(-/-) background revealed reduced Shh and Gli1 expression in the antra compared to wild type controls (WT). Gli2 expression in the Gast(-/-) corpus was unchanged. However in the hyperplastic Gast(-/-) antra, Gli2 expression increased in both the mesenchyme and epithelium, whereas expression in WT mice remained exclusively mesenchymal. These observations suggested that Gli2 is differentially regulated in the hyperplastic Gast(-/-) antrum versus the corpus and by a Shh ligand-independent mechanism. Moreover, the proinflammatory cytokines Il-1β and Il-11, which promote gastric epithelial proliferation, were increased in the Gast(-/-) stomach along with Infγ. To test if inflammation could account for elevated epithelial Gli2 expression in the Gast(-/-) antra, the human gastric cell line AGS was treated with IL-1β and was found to increase GLI2 but decrease GLI1 levels. IL-1β also repressed human GAST gene expression. Indeed, GLI2 but not GLI1 or GLI3 expression repressed gastrin luciferase reporter activity by ∼50 percent. Moreover, chromatin immunoprecipitation of GLI2 in AGS cells confirmed that GLI2 directly binds to the GAST promoter. Using a mouse model of constitutively active epithelial GLI2 expression, we found that activated GLI2 repressed Gast expression but induced Il-1β gene expression and proliferation in the gastric antrum, along with a reduction of the number of G-cells. In summary, epithelial Gli2 expression was sufficient to stimulate Il-1β expression, repress Gast gene expression and increase proliferation, leading to antral hyperplasia.
    PLoS ONE 10/2012; 7(10):e48039. DOI:10.1371/journal.pone.0048039 · 3.23 Impact Factor
Show more