Study on Association between Single Nucleotide Polymorphisms of MMP7, MMP8, MMP9 Genes and Development of Gastric Cancer and Lymph Node Metastasis

Ji Hye Kim; Jung-A Pyun; Kwang Jae Lee; Sung Won Cho; Kyu Bum Kwack

doi:10.4166/kjg.2011.58.5.245

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Kim, Pyun, Lee, Cho, and Kwack: Study on Association between Single Nucleotide Polymorphisms of MMP7, MMP8, MMP9 Genes and Development of Gastric Cancer and Lymph Node Metastasis

Original Article

Korean J Gastroenterol 2011;58(5):245-251.

Published online: 4 October 2011

DOI: https://doi.org/10.4166/kjg.2011.58.5.245

Study on Association between Single Nucleotide Polymorphisms of MMP7, MMP8, MMP9 Genes and Development of Gastric Cancer and Lymph Node Metastasis

Ji Hye Kim, Jung-A Pyun, Kwang Jae Lee¹, Sung Won Cho¹, Kyu Bum Kwack

Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Korea

¹Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea

Correspondence to: Kyu Bum Kwack, Department of Biomedical Science, College of Life Science, CHA University, 222, Yatap-dong, Bundang-gu, Seongnam 463-836, Korea. Tel: +82-31-725-8376, Fax: +82-31-725-8350, E-mail: kbkwack@cha.ac.kr, kbkwack@gmail.com

Received 6 April 2011 Accepted 17 June 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Matrix metallopeptidase (MMP) is known to be involved in tumor invasion and metastasis of cancer. This study investigated the association of MMP7 rs11568818, MMP8 rs11225395, MMP9 rs17576 and rs2250889 with gastric cancer (GC) development and lymph node metastasis (LNM).

Methods

Samples were obtained from 326 chronic gastritis (CG) and 153 GC patients and genotyped by using the GoldenGate^® method. Chi-square test was performed to identify the difference of allele distribution between each group (CG vs. GC; CG vs. with LNM GC). The associations of genotype with risk of GC and LNM were estimated by odds ratio and the 95% confidence interval was calculated by logistic regression adjusting for age and sex.

Results

The allele and genotype frequencies of MMP7 rs11568818, MMP8 rs11225395, MMP9 rs17576 and rs2250889 were not associated with the development of GC and LNM.

Conclusions

In summary, MMP7 rs11568818, MMP8 rs11225395 MMP9 rs17576 and rs2250889 were not associated with the GC development and LNM in Korean population.

Keywords: Stomach neoplasms, Lymph node metastasis, Metalloproteinase 7, Metalloproteinase 8, Metalloproteinase 9

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Table 1.

Clinicopathological Characteristics of Patients with Chronic Gastritis and Gastric Cancer

Characteristic	Chronic gastritis n (%)	Gastric cancer n (%)	p-value^a
Patients (n)	326	153
Age (mean, yr)	55.2	57.8
≤50	103 (31.6)	46 (30.07)
51–60	129 (39.57)	40 (26.14)	＜0.0001
60–70	93 (28.53)	46 (30.07)
≥71	1 (0.31)	21 (13.73)
Gender
Male	160 (49.1)	101 (66)	0.0005
Female	166 (50.9)	52 (34)	0.0005
Lymph node metastasis
N0	−	94 (61.4)
N1	−	32 (20.9)
N2	−	22 (14.4)
N3	−	5 (3.3)
Tumor invasion
T1		69 (45.1)
T2		37 (24.2)
T3		44 (28.8)
T4		3 (2)
Metastasis
M0		152 (99.3)
M1		1 (0.7)
Staging
IA		62 (40.5)
IB		27 (17.6)
II		22 (14.4)
IIIA		20 (13.1)
IIIB		13 (8.5)
IV		9 (5.9)
Histological classification
Diffuse		18 (11.80)
Intestinal		117 (76.50)
Mixed		7 (4.60)
Unclassified		11 (7.20)

^a chi-square test.

Table 2.

Genotype Distribution of MMP7, MMP8, and MMP9 Polymorphisms and Their Impact on Gastric Cancer Risk

Gene/SNP	Chronic gastritis n (%)	Gastric cancer n (%)	Model	OR	95% CI	p-value
MMP7 rs11568818
AA	280 (85.89)	128 (83.66)	Allele	1.195	0.725–1.970	0.484^a
AG	45 (13.8)	24 (15.69)	Additive	1.104	0.655–1.860	0.711^b
GG	1 (0.31)	1 (0.65)	Dominant	1.087	0.630–1.874	0.765^b
			Recessive	2.069	0.107–40.009	0.630^b
MMP8 rs11225395
GG	150 (47.62)	67 (45.27)	Allele	1.006	0.748–1.352	0.969^a
AG	127 (40.32)	67 (45.27)	Additive	1.016	0.755–1.369	0.914^b
AA	38 (12.06)	14 (9.46)	Dominant	1.121	0.748–1.678	0.580^b
			Recessive	0.806	0.417–1.556	0.520^b
MMP9 rs17576
GG	153 (47.37)	75 (50.34)	Allele	1.100	0.813–1.487	0.538^a
AG	143 (44.27)	63 (42.28)	Additive	0.902	0.656–1.239	0.524^b
AA	27 (8.36)	11 (7.38)	Dominant	0.865	0.581–1.289	0.477^b
			Recessive	0.936	0.443–1.976	0.861^b
MMP9 rs2250889
CC	161 (49.85)	85 (55.92)	Allele	0.856	0.627–1.169	0.329^a
GC	143 (44.27)	58 (38.16)	Additive	0.844	0.607–1.173	0.313^b
GG	19 (5.88)	9 (5.92)	Dominant	0.789	0.531–1.174	0.243^b
			Recessive	0.948	0.411–2.189	0.901^b

^a chi-square test

^b logistic regression.

Table 3.

Genotype Distribution of MMP7, MMP8, and MMP9 Polymorphisms and Their Impact on LNM risk

Gene/SNP	Chronic gastritis n (%)	With LNM gastric cancer n (%)	Model	OR	95% CI	p-value
MMP7rs11568818
AA	280 (85.89)	46 (77.97)	Allele	1.594	0.834–3.047	0.156^a
AG	45 (13.8)	13 (22.03)	Additive	1.442	0.709–2.935	0.312^b
GG	1 (0.31)	0 (0)	Dominant	1.466	0.713–3.015	0.298^b
			Recessive	0.000	−	0.992^b
MMP8rs11225395
GG	150 (47.62)	30 (50.85)	Allele	1.127	0.734–1.731	0.584^a
AG	127 (40.32)	23 (38.98)	Additive	0.896	0.577–1.390	0.623^b
AA	38 (12.06)	6 (10.17)	Dominant	0.856	0.476–1.540	0.604^b
			Recessive	0.895	0.348–2.299	0.818^b
MMP9rs17576
GG	153 (47.37)	26 (44.07)	Allele	0.999	0.653–1.530	0.998^a
AG	143 (44.27)	30 (50.85)	Additive	1.015	0.641–1.608	0.950^b
AA	27 (8.36)	3 (5.08)	Dominant	1.160	0.649–2.071	0.617^b
			Recessive	0.605	0.172–2.126	0.433^b
MMP9rs2250889
CC	161 (49.85)	30 (50.85)	Allele	0.956	0.651–1.485	0.841^a
GC	143 (44.27)	26 (44.07)	Additive	0.977	0.608–1.568	0.922^b
GG	19 (5.88)	3 (5.08)	Dominant	1.030	0.578–1.835	0.921^b
			Recessive	0.746	0.206–2.701	0.655^b

SNP, single nucleotide polymorphism; MMP, matrix metalloproteinase; LNM, lymph node metastasis.

^a chi-square test

^b logistic regression.

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