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Effect of polymorphisms of IL‐1β and TNF‐α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa
Author(s) -
Tahara Tomomitsu,
Shibata Tomoyuki,
Nakamura Masakatsu,
Yamashita Hiromi,
Yoshioka Daisuke,
Okubo Masaaki,
Yonemura Joh,
Kamiya Yoshio,
Ishizuka Takamitsu,
Hirata Ichiro,
Arisawa Tomiyasu
Publication year - 2011
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20759
Subject(s) - biology , methylation , genotype , carcinogenesis , cpg site , dna methylation , cdh1 , gene , helicobacter pylori , gastric mucosa , candidate gene , methylenetetrahydrofolate reductase , tumor necrosis factor alpha , microbiology and biotechnology , genetics , stomach , immunology , gene expression , cadherin , biochemistry , cell
Abstract CpG island hyper methylation (CIHM) is one of the major events in gastric carcinogenesis. To evaluate the influence of host genetic factors in CIHM related carcinogenesis, we investigated the association between common polymorphisms in IL‐1β and TNF‐α genes, with CIHM status in the nonneoplastic gastric mucosa. Polymorphisms in the IL‐1β gene (‐31T>C and ‐511C>T) and the TNF‐α gene (‐857C>T) were genotyped in 385 cancer‐free subjects. CIHM of four candidate genes: p16 (INK4a), p14 (ARF), E‐cadherin (CDH1), and death‐associated protein kinase (DAP‐kinase), were determined by methylation‐specific‐polymerase chain reaction (MSP). CIHM high was defined as two or more CpG islands methylated. CIHM of all four genes and CIHM high were significantly associated with Helicobacter pylori infection status. In over all, significant marginal association was found between IL‐1β‐511 TT genotype and reduced susceptibility to CIHM of DAP‐kinase (adjusted OR = 0.48, 95% CI = 0.29–0.78) and CIHM high (adjusted OR = 0.53, 95% CI = 0.32–0.86). This association was more enhanced in subjects 65 yr or younger age. We also found positive association between TNF‐α‐857T carrier and increased susceptibility to CIHM of CDH (adjusted OR = 1.78, 95% CI = 1.01–3.16), and CIHM high (adjusted OR = 1.86, 95% CI = 1.04–3.33) in the same generation. The mean number of CIHM was lower in subjects with IL‐1β‐511TT genotype, while the mean number was higher in subjects with TNF‐α‐857 T carrier especially in subjects 65 yr and younger patients. IL‐1β‐511 TT genotype is associated with reduced susceptibility to CIHM especially in younger generation. Furthermore, the TNF‐α‐857T carrier is associated with increased susceptibility of CIHM in the same generation. © 2011 Wiley Periodicals, Inc.