Polymorphisms in Inflammatory Response Genes and Their Association With Gastric Cancer: A HuGE Systematic Review and Meta-Analyses

Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
American journal of epidemiology (Impact Factor: 5.23). 02/2011; 173(3):259-70. DOI: 10.1093/aje/kwq370
Source: PubMed


To evaluate the association between gastric cancer susceptibility and inflammation-related gene polymorphisms, the authors conducted a series of meta-analyses using a predefined protocol. Genes investigated were those coding for the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic subsite, by Helicobacter pylori infection status, by geographic location (Asian or non-Asian study population), and by a quantitative index of study quality. All published literature and meeting abstracts from the period 1990-2006 were considered. Results consistently supported increased cancer risk for IL1RN2 carriers; the increased risk was specific to non-Asian populations and was seen for intestinal and diffuse cancers, distal cancers, and, to a lesser extent, cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive cases and controls also showed significant associations with both carrier status and homozygosity status. In Asian populations, reduced risk was observed in association with IL1B-31C carrier status. This effect was also observed in analyses restricted to high-quality studies. These results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection, and country of origin. Study quality considerations, both laboratory and epidemiologic, can also affect results and may explain, in part, the variability in results published to date.

Download full-text


Available from: Paulo Canedo,
  • Source
    • "In addition, an animal model has demonstrated that elevated levels of IL-1β are sufficient to induce dysplasia and gastric cancer 32 . Subjects carrying the IL1B-511T allele are high producers of IL-1β 33 , and multiple studies confirm this polymorphism as a risk factor for intestinal-type gastric adenocarcinoma in Caucasian populations (or in non-Asian populations) but not in Asian populations 34 , 35 . Carriers of IL1RN2 of non-Asian origin have shown an increased risk of gastric adenocarcinoma (intestinal and diffuse types) predominantly for distal tumors 35 . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer.
    09/2013; 44(3):192-201.
  • Source
    • "Another meta-analysis based on fourteen studies on the IL1B +3954 polymorphism covering data from six Asian and eight non-Asian populations showed lack of statistical significance between presence of studied polymorphism and risk of gastric cancer. In general, all results were similar in magnitude when analyses were restricted to H. pylori-positive cases and controls (Persson et al. 2011). The results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection and country of origin. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.
    Archivum Immunologiae et Therapiae Experimentalis 08/2013; 61(6). DOI:10.1007/s00005-013-0245-y · 3.18 Impact Factor
  • Source
    • "While previously published meta - analyses have reported only on prostate cancer ( Shao et al . , 2011 ; Zou et al . , 2011 ) , hepatocellular carcinoma ( Wei et al . , 2011 ) , and gastric cancer ( Chen et al . , 2010 ; Persson et al . , 2011 ; Xue et al . , 2012 ) , we were able to provide a complete description of the role of the IL - 10 - 819C / T polymorphism in cancer risk . Our meta - analysis included two new studies ( Bei et al . , 2011 ; Liu et al . , 2010b ) on hepatocellular carcinoma that were not included in a 2011 meta - analysis ( Wei et al . , 2011 ) and four"
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The aim of the present work was to perform a meta-analysis to evaluate the association between the interleukin 10 (IL-10) -819C/T (rs1800871) polymorphism and cancer risk. A total of 73 studies, including 15,942 cancer cases and 22,336 controls, were identified in this meta-analysis. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Overall, no significant association was identified between the IL-10 -819C/T polymorphism and cancer risk. In the subgroup analyses, the T allele and TT genotype were associated with a moderately reduced cancer risk in the Asian population (T allele vs. C allele: OR=0.93, 95%CI: 0.87, 0.99; TT vs. CC: OR=0.86, 95%CI: 0.76, 0.98; TT vs. CT/CC: OR=0.90, 95%CI: 0.82, 0.98). Individuals who were homozygous for the T allele (TT) were found to be associated with significantly reduced gastric cancer risk in the Asian population. The heterozygous variant (CT) and the dominant model (TT/CT vs. CC) were associated with an increased risk for cervical and ovarian cancer. However, the IL-10 -819C/T polymorphism was not significantly associated with breast cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, prostate cancer, lymphoma, or melanoma. The depressed cancer risk of the TT genotype occurred in the studies of hospital-based case-control studies and the studies recruited less than 500 subjects, but no statistically significant results were found in the stratified analyses using genotyping method. The results suggest that the IL-10 -819TT genotype may be a protective factor for cancer in Asians, especially gastric cancer. In contrast, the CT genotype and the dominant model could be risk factors for cervical and ovarian cancer. The importance of stratifying by ethnicity, cancer type, study design, and sample size needs to be standardized in future studies, together with considering the association between the IL-10 -819C/T polymorphism and cancer risk. Furthermore, the linkage of -819C/T with other polymorphisms of the IL-10 gene may help explain the variability in findings.
    Omics: a journal of integrative biology 04/2013; 17(4):200-14. DOI:10.1089/omi.2012.0089 · 2.36 Impact Factor
Show more