Profiles of Gene Polymorphisms in Cytokines and Toll-Like Receptors with Higher Risk for Gastric Cancer

Profiles of Gene Polymorphisms in Cytokines and Toll-Like Receptors with Higher Risk for Gastric Cancer

Background Chronic inflammation and gastric carcinogenesis show a close association, so gene polymorphisms that modify the intensity of the inflammatory response may contribute to variations in gastric cancer risk. Aims The purpose of this study was to investigate the combined effect of the pro- and...

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Bibliographic Details
Published in:Digestive diseases and sciences Vol. 58; no. 4; pp. 978 - 988
Main Authors: de Oliveira, Juliana Garcia, Rossi, Ana Flávia Teixeira, Nizato, Daniela Manchini, Miyasaki, Kenji, Silva, Ana Elizabete
Format: Journal Article
Language:English
Published: Boston Springer US 01-04-2013
Springer
Springer Nature B.V
Subjects:
Adult
Aged
Aged, 80 and over
Biochemistry
Brazil
Cancer
Case-Control Studies
Female
Gastroenterology
Genes
Genetic aspects
Genetic polymorphisms
Genetic Predisposition to Disease
Health aspects
Hepatology
Humans
Inflammation
Interleukins - genetics
Male
Medicine
Medicine & Public Health
Middle Aged
Oncology
Oncology, Experimental
Original Article
Polymorphism, Genetic
Risk factors
Stomach cancer
Stomach Neoplasms - genetics
Toll-Like Receptors - genetics
Transplant Surgery
Tumor necrosis factor
Young Adult
Brazil
Toll-like receptors
Gene polymorphisms
Chronic gastritis
Cytokines
Gastric cancer
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Summary:Background Chronic inflammation and gastric carcinogenesis show a close association, so gene polymorphisms that modify the intensity of the inflammatory response may contribute to variations in gastric cancer risk. Aims The purpose of this study was to investigate the combined effect of the pro- and anti-inflammatory cytokines and toll-like receptors polymorphisms on the chronic gastritis and gastric cancer risk in a Brazilian population sample. Methods We evaluated 669 DNA samples (200 of gastric cancer [GC], 229 of chronic gastritis [CG], and 240 of healthy individuals [C]). Ten polymorphisms were genotyped: IL - 1RN and TLR2 -196 to -174 del using the allele-specific PCR method and TNF - A (rs1800629; rs1799724), TNF - B (rs909253) , IL - 8 (rs4073; rs2227532) , IL - 10 (rs1800872) and TLR4 (rs4986790; rs4986791) using PCR–RFLP. Results Polymorphisms TNF - A - 308G/A, IL - 8 - 251A/T, TNF - B  +  252A/G and TLR4  +  1196C/T were not associated with risk of any gastric lesion. However, an association with increased risk for GC was observed for polymorphisms IL - 1RNL/2 ( p  < 0.001), TNF - A - 857C/T ( p  = 0.022), IL - 8 - 845T/C ( p  < 0.001) , IL - 10 - 592C/A ( p  < 0.001), TLR2ins/del ( p  < 0.001), and TLR4  +  896A/G ( p  = 0.033). In CG, an association was observed only with polymorphisms IL - 1RNL/2 and IL - 10 - 592A/C ( p  < 0.001 for both). A combined analysis of these six polymorphisms associated with GC revealed a profile with two to four combined genotypes which confer a higher risk of gastric carcinogenesis, with an OR increased 2.95-fold to 50.4-fold, highlighting the combinations IL - 1RN2/TNF - A - 857T/IL - 8 - 845C, IL - 1RN2/IL - 8 - 845C/TLR2del, IL - 1RN2/IL - 10 - 592A/TLR4  +  896G, IL - 10 - 592A/TLR2del/TLR4  +  896G, and IL - 1RN2/TNFA - 857T/IL8 - 845C/TLR2del. Conclusions Our findings evidenced that the combined effect of polymorphisms in genes involved in the inflammatory process may potentiate the risk of gastric cancer, thus emphasizing the importance of evaluating multiple polymorphisms together.
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ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-012-2460-5