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
    • "Gastric cancer (GC) represents a major health problem worldwide (Jemal et al. 2011). Although it has been described a possible association between GC risk and genetic polymorphism of several genes (mainly STAT3 (Yuan et al. 2014), innate immunity genes (Kim et al. 2013), TLR4 (Zhou et al., 2014), and genes involved in the inflammatory responses (Camargo et al. 2006; Loh et al. 2009; Persson et al. 2011; Wen et al. 2014), a critical role has been suggested for a number of environmental factors such as infectious agents (Helicobacter pylori (Ferreira et al. 2014; Wang et al. 2014), Epstein–Barr Virus (Murphy et al. 2009)), tobacco smoke (Santibanez et al. 2015), dietary factors (Joossens et al. 1996; Gonzalez et al. 2006), and environmental pollutants linked with vehicular traffic (Chiu et al. 2011), industrial facilities (Garcia-Perez et al. 2012), or contaminated soil, water, and food (Loizidou and Kapetanios 1993; Morales-Suarez-Varela et al. 1995; Beaumont et al. 2008; Li et al. 2013; Crocetti et al. 2014; Zhao et al. 2014; Gunduz et al. 2015), possibly as a result of gene–environment interactions through epigenetic mechanisms affecting gene expression (David and Meltzer 2010). A relationship between waste management and GC has been previously suggested. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Municipal waste landfills (MWLs) have been linked with some malignancies, but data about gastric cancer (GC) are still uncertain. Methods: Number of deaths from GC, death rates, and odds ratios (ORs) were calculated considering all residents in the 258 towns in the Apulia Region (4,099,547 subjects, years 2006-2009), living within 3 km from each of the 16 regional MWLs (n = 716,404) or in control areas (n = 3,383,143). Results: Males living close to MWLs showed a higher death rate for GC, a twofold higher mean number of GC deaths and higher adjusted ORs of GC, compared with controls areas. Conclusions: In a large population and over a wide time period, an increased risk of death from GC has been shown in males living in communities close to MWLs. Primary prevention policies acting through more sustainable waste management might probably partially reduce deaths from GC in areas with MWLs.
    Full-text · Article · Nov 2015 · International Journal of Environmental Health Research
  • Source
    • "That study showed a significant association between TNF-í µí»¼ −238 and high risk of GC. In contrary, another meta-analysis showed no significant association concerning TNF-í µí»¼ −238 frequency for genotypes G/G, A/A, and G/A[6,15,20]. However, no integrated analysis has been made to get a definitive conclusion of whether TNF-í µí»¼ −238 (G/A) is associated with GC[19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphisms in tumor necrosis factor alpha (TNF- α ) gene are emerging as key determinants of gastric diseases. The TNF- α −308 (G/A) and TNF- α −238 (G/A) single-nucleotide polymorphisms SNPs are the most extensively studied. However, all these studies are conducted in Caucasian and Asian populations. Thus, for the first time in Africa, we sought to investigate whether polymorphisms in TNF- α gene were associated with the development of gastric pathology in Morocco. Two SNPs located in the promoter region (positions −308 and −238) in TNF- α gene were genotyped in 244 individuals (170 patients and 74 healthy controls). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression analysis. The TNF- α −238 (G/A) genotype was significantly associated with a high risk of gastritis and gastric cancer (GC) ( P = 0.001 and P = 0.002 , resp.). Furthermore, a new polymorphism located in the promoter region at position −193 in TNF- α gene was identified. The distribution of this SNP was markedly different in patients suffering from ulcers. The association between TNF- α −193 (G/A) genotype and high risk of ulcer was significant ( P = 0.03 ). These results suggest that the TNF- α −193 (G/A) allele has a protective function against gastric cancer by developing ulcer.
    Full-text · Article · Oct 2015 · Mediators of Inflammation
  • Source
    • "There was not enough data for a pooled analysis of advanced disease for DFS (n = 2). Previous studies suggested genetic differences between gastric cancers dependent on geographic location747576. We therefore evaluated the prognostic value of FITC detection separately for these cohorts. These analyses showed a significant association between FITC detection and OS for Asian population (3.31; 2.77 -3.95; n = 38; I² = 78%)[11-13, 16, 18, 20-22, 24, 26, 30-35, 38, 40, 41, 43, 45, 46, 48, 52, 55-57, 60-68]as well as Western population (3.17; 2.50 -4.01; n = 13; I² = 48%)[10, 15, 17, 19, 28, 39, 44, 47, 49-51, 59, 69]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Despite continuously improving therapies, gastric cancer still shows poor survival in locally advanced stages with local recurrence rates of up to 50% and peritoneal recurrence rates of 17% after curative surgery. We performed a systematic review with meta-analyses to clarify whether positive intraperitoneal cytology (IPC) indicates a high risk of disease recurrence and poor overall survival in gastric cancer. Methods: Multiple databases were searched in December 2014 to identify studies on the prognostic significance of positive intraperitoneal cytology in gastric cancer, including: Medline, Biosis, Science Citation Index, Embase, CCMed and publisher databases. Hazard ratios (HR) and associated 95% confidence intervals (CI) were extracted from the identified studies. A meta-analysis was performed using a random-effects model on overall survival, disease-free survival and peritoneal recurrence free survival. Results: A total of 64 studies with a cumulative sample size of 12,883 patients were included. Cytology, quantitative real time polymerase chain reaction (PCR) or both were performed in 35; 21 and 8 studies, respectively. Meta analyses revealed free intraperitoneal tumor cells (FITC) to be associated with poor overall survival in univariate (HR 3.27; 95% CI 2.82 - 3.78]) and multivariate (HR 2.45; 95% CI 2.04 - 2.94) analysis and poor peritoneal recurrence free survival in univariate (4.15; 95% CI 3.10 - 5.57) and multivariate (3.09; 95% CI 2.02 - 4.71) analysis. Subgroup analysis showed this effect to be independent of the detection method, Western or Asian origin or the time of publication. Conclusions: FITC oder positive peritoneal cytology is associated with poor survival and increased peritoneal recurrence in gastric cancer.
    Preview · Article · Sep 2015 · Oncotarget
Show more