Genetic polymorphisms in the MMP-7 gene and breast cancer survival.
Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression has been shown to be associated with tumor invasion, metastasis and survival for a variety of cancers. We systematically evaluated single nucleotide polymorphisms (SNPs) in MMP-7 in relation to breast cancer survival in a large follow-up study. Included were 1,079 breast cancer cases that were recruited from 1996 to 1998 and followed for a median of 7.1 years as part of the Shanghai Breast Cancer Study (SBCS). Eleven SNPs, including 2 known functional promoter SNPs, were analyzed using the Affymetrix Targeted Genotyping System. Associations with survival were evaluated by Cox proportional hazards regression and Kaplan-Meier functions. Statistically significant associations with disease-free and/or overall survival (OS) were found for 5 polymorphisms; these associations were explained primarily by 2 SNPs (rs11568818 and rs11225297) that were in high linkage disequilibrium (LD) with the others. Patients homozygous for the rs11568818 rare allele (G) had a significantly worse prognosis (OS HR: 6.7, 95% CI: 2.4-18.6) than patients homozygous for the common allele (A). Significantly improved survival was seen for patients with the rs11225297 T allele, and this association occurred in a dose-response manner; patients with AT (OS HR: 0.7, 95% CI: 0.5-0.9) and TT (OS HR: 0.3, 95% CI: 0.1-0.8) fared better than patients with AA (p-value for trend: 0.001). Thus, common MMP-7 genetic polymorphisms were found to be significant determinants of survival among Chinese women with breast cancer.
Beeghly-Fadiel
Alicia
A
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA.
Shu
Xiao-Ou
XO
Long
Jirong
J
Li
Chun
C
Cai
Qiuyin
Q
Cai
Hui
H
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
Gynecol Oncol. 2006 Apr;101(1):92-6
16278009
Carcinogenesis. 2006 May;27(5):1113-20
16474169
Cancer Res. 2001 Jan 15;61(2):577-81
11212252
Clin Cancer Res. 2006 Dec 1;12(23):6998-7003
17145820
Genome Res. 2005 Feb;15(2):269-75
15687290
J Gastroenterol. 2004;39(5):434-40
15175941
Jpn J Clin Oncol. 1999 Feb;29(2):58-62
10089944
J Clin Invest. 2000 Jan;105(2):143-50
10642592
Int J Cancer. 1998 Apr 17;79(2):187-94
9583735
Clin Cancer Res. 2004 Apr 15;10(8):2832-45
15102692
Biochemistry. 1989 Jun 27;28(13):5327-34
2550050
Cancer Res. 2004 Feb 1;64(3):836-9
14871809
Int J Biochem Cell Biol. 1996 Feb;28(2):123-36
8729000
Clin Exp Metastasis. 1998 Oct;16(7):577-85
9932604
Oncol Rep. 2006 Oct;16(4):823-30
16969501
J Invest Dermatol. 1995 Aug;105(2):190-6
7636300
Br J Cancer. 2003 Dec 1;89(11):2116-21
14647147
Br J Cancer. 2006 Aug 21;95(4):506-14
16880790
Br J Cancer. 2006 Sep 18;95(6):744-51
16940985
Genet Epidemiol. 2005 Dec;29(4):299-312
16240443
Biochem Biophys Res Commun. 2005 Aug 5;333(3):1011-6
15964556
Cancer Metastasis Rev. 2006 Mar;25(1):9-34
16680569
Clin Chem. 2003 Nov;49(11):1940-2
14578330
Br J Cancer. 2001 May 18;84(10):1317-21
11355941
Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1834-9
11701474
Cancer Res. 2005 Jun 15;65(12):5015-9
15958542
Cancer. 2000 May 15;88(10):2201-9
10820340
Clin Cancer Res. 2002 Jan;8(1):144-8
11801551
Br J Cancer. 2007 Mar 26;96(6):903-11
17342087
Int J Cancer. 2000 Jul 15;87(2):295-300
10861490
Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6037-42
17062678
Neoplasia. 2001 Nov-Dec;3(6):459-68
11774028
Jpn J Clin Oncol. 2005 Dec;35(12):739-44
16314344
Gut. 1999 Aug;45(2):252-8
10403738
Hepatogastroenterology. 2004 May-Jun;51(57):900-5
15143943
Bioinformatics. 2005 Jan 15;21(2):263-5
15297300
J Clin Oncol. 2001 Feb 15;19(4):1118-27
11181677
Genes Dev. 2002 Feb 1;16(3):307-23
11825873
Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6673-80
18006768
Gastric Cancer. 2000 Sep 29;3(2):63-70
11984713
Nutr Cancer. 2007;58(2):239-46
17640171
J Cell Sci. 2001 Jan;114(Pt 1):111-118
11112695
Cancer Res. 2008 Aug 1;68(15):6453-9
18648013
Int J Cancer. 2005 Mar 10;114(1):19-31
15523695
Nat Rev Cancer. 2002 Mar;2(3):161-74
11990853
Clin Cancer Res. 2005 Aug 15;11(16):6012-9
16115946
APMIS. 2005 Apr;113(4):246-55
15865605
Nat Genet. 2006 Oct;38(10):1166-72
16998491
Cancer. 1995 Mar 15;75(6 Suppl):1516-9
7889484
Nature. 2003 Dec 18;426(6968):789-96
14685227
Curr Biol. 1999 Dec 16-30;9(24):1441-7
10607586