title: Toll-like receptor 2 -196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer.
abstract: Toll like receptors (TLR) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. The -196 to -174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2-196 to -174del polymorphism on the occurrence of non-cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non-cancer patients with abdominal discomfort and 146 healthy controls. The -196 to -174del TLR2 polymorphism was investigated using the allele-specific polymerase chain reaction method in all of the subjects. The -196 to -174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio [OR] = 6.06; 95% confidence interval [CI] = 1.86-19.72). Similarly, the frequency of the -196 to -174del/del genotype was significantly higher among NCGC patients than in non-cancer patients (adjusted OR = 2.02; 95% CI = 1.22-3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12-3.60) and diffuse-type (OR = 2.05; 95% CI = 1.11-3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the -196 to -174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population.
authors: Department of Gastroenterology, Fujita Health University School of Medicine, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
authors: Tomomitsu
authors: T
authors: Tahara
authors: Tomiyasu
authors: T
authors: Arisawa
authors: Fangyu
authors: F
authors: Wang
authors: Tomoyuki
authors: T
authors: Shibata
authors: Masakatsu
authors: M
authors: Nakamura
authors: Mikijyu
authors: M
authors: Sakata
authors: Ichiro
authors: I
authors: Hirata
authors: Hiroshi
authors: H
authors: Nakano
mesh_terms: D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000453:epidemiology; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*
chemical_list: D051195:Toll-Like Receptor 2
references: J Biol Chem. 2001 Nov 30;276(48):44856-64
references: 11546774
references: Gastroenterology. 1995 Sep;109(3):681-91
references: 7657096
references: JAMA. 2004 Jan 14;291(2):187-94
references: 14722144
references: Acta Pathol Microbiol Scand. 1965;64:31-49
references: 14320675
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71
references: 11095740
references: Curr Opin Immunol. 2002 Feb;14(1):103-10
references: 11790539
references: J Biol Chem. 2000 May 26;275(21):16064-72
references: 10747974
references: Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):639-42
references: 9264278
references: Gastroenterology. 1995 Jan;108(1):65-74
references: 7806065
references: Helicobacter. 2005 Jun;10(3):193-204
references: 15904477
references: Gastroenterology. 2002 Jul;123(1):92-105
references: 12105837
references: Infect Immun. 2005 Mar;73(3):1523-31
references: 15731050
references: N Engl J Med. 2001 Sep 13;345(11):784-9
references: 11556297
references: Int J Cancer. 1985 Feb 15;35(2):173-7
references: 3871738
references: J Clin Invest. 1994 Jul;94(1):4-8
references: 8040281
references: CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29
references: 14974761
references: Nat Rev Immunol. 2001 Nov;1(2):135-45
references: 11905821
references: Nat Immunol. 2001 Aug;2(8):675-80
references: 11477402
references: Endoscopy. 1998 Oct;30(8):669-74
references: 9865554
references: Gut. 2005 Mar;54(3):330-5
references: 15710978
references: Gastroenterology. 2003 Aug;125(2):364-71
references: 12891537
references: Scand J Gastroenterol. 1990 Dec;25(12):1223-6
references: 2274743
references: Clin Exp Allergy. 2004 Feb;34(2):177-83
references: 14987294
references: Infect Immun. 1997 Aug;65(8):3218-24
references: 9234778
references: J Biol Chem. 2003 Aug 29;278(35):32552-60
references: 12807870
references: Nature. 2000 Mar 23;404(6776):398-402
references: 10746728
references: Nat Immunol. 2001 Oct;2(10):947-50
references: 11547333
references: JAMA. 1994 Jul 6;272(1):65-9
references: 8007082
references: Gastroenterology. 2001 Oct;121(4):784-91
references: 11606491
references: Gastroenterology. 1998 Jun;114(6):1169-79
references: 9609753
references: Lancet. 1975 Jul 12;2(7924):58-60
references: 49653
references: Gastroenterology. 1997 Oct;113(4):1099-109
references: 9322504
references: Int J Cancer. 2003 May 1;104(5):617-23
references: 12594817
references: N Engl J Med. 1991 Oct 17;325(16):1127-31
references: 1891020
references: Lancet. 1994 Jan 22;343(8891):243-4
references: 7904707
references: Am J Surg Pathol. 1995;19 Suppl 1:S37-43
references: 7762738