Toll-like receptor 2 -196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer.
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.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
Arisawa
Tomiyasu
T
Wang
Fangyu
F
Shibata
Tomoyuki
T
Nakamura
Masakatsu
M
Sakata
Mikijyu
M
Hirata
Ichiro
I
Nakano
Hiroshi
H
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*
D051195:Toll-Like Receptor 2
J Biol Chem. 2001 Nov 30;276(48):44856-64
11546774
Gastroenterology. 1995 Sep;109(3):681-91
7657096
JAMA. 2004 Jan 14;291(2):187-94
14722144
Acta Pathol Microbiol Scand. 1965;64:31-49
14320675
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71
11095740
Curr Opin Immunol. 2002 Feb;14(1):103-10
11790539
J Biol Chem. 2000 May 26;275(21):16064-72
10747974
Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):639-42
9264278
Gastroenterology. 1995 Jan;108(1):65-74
7806065
Helicobacter. 2005 Jun;10(3):193-204
15904477
Gastroenterology. 2002 Jul;123(1):92-105
12105837
Infect Immun. 2005 Mar;73(3):1523-31
15731050
N Engl J Med. 2001 Sep 13;345(11):784-9
11556297
Int J Cancer. 1985 Feb 15;35(2):173-7
3871738
J Clin Invest. 1994 Jul;94(1):4-8
8040281
CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29
14974761
Nat Rev Immunol. 2001 Nov;1(2):135-45
11905821
Nat Immunol. 2001 Aug;2(8):675-80
11477402
Endoscopy. 1998 Oct;30(8):669-74
9865554
Gut. 2005 Mar;54(3):330-5
15710978
Gastroenterology. 2003 Aug;125(2):364-71
12891537
Scand J Gastroenterol. 1990 Dec;25(12):1223-6
2274743
Clin Exp Allergy. 2004 Feb;34(2):177-83
14987294
Infect Immun. 1997 Aug;65(8):3218-24
9234778
J Biol Chem. 2003 Aug 29;278(35):32552-60
12807870
Nature. 2000 Mar 23;404(6776):398-402
10746728
Nat Immunol. 2001 Oct;2(10):947-50
11547333
JAMA. 1994 Jul 6;272(1):65-9
8007082
Gastroenterology. 2001 Oct;121(4):784-91
11606491
Gastroenterology. 1998 Jun;114(6):1169-79
9609753
Lancet. 1975 Jul 12;2(7924):58-60
49653
Gastroenterology. 1997 Oct;113(4):1099-109
9322504
Int J Cancer. 2003 May 1;104(5):617-23
12594817
N Engl J Med. 1991 Oct 17;325(16):1127-31
1891020
Lancet. 1994 Jan 22;343(8891):243-4
7904707
Am J Surg Pathol. 1995;19 Suppl 1:S37-43
7762738