Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese population.
Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and their over-expression is often associated with unfavorable survival of non-small cell lung cancer (NSCLC). Because genetic variants can alter expression level or biological activity of MMPs, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in key MMP genes may be associated with the survival of NSCLC patients. We selected and genotyped 14 putative functional SNPs in six MMP genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) using PCR-RFLP methods in 561 NSCLC patients. Kaplan-Meier method with the log-rank test and Cox proportional hazard models were used for the survival analyses. The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively). The C-1562T and Arg668Gln loci were in complete linkage disequilibrium (r(2) = 1). Patients carrying the 668Gln allele had improved survival with a median survival time (MST) of 51.6 months, compared with 21.8 months for those with the 668Arg/Arg genotype (log-rank p = 0.010). In contrast, the 279Gln/Gln genotype was associated with a significantly shortened MST (17.3 months, log-rank p = 0.030) in the recessive model. In the final multivariate Cox regression model, 279Gln/Gln was identified as an independent prognostic factor with an adjusted hazard ratio of 1.60 (95% confidence interval 1.07-2.41). The MMP9 Arg279Gln and Arg668Gln SNPs are potential predictors of survival in NSCLC patients.
Jin
Guangfu
G
Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
Miao
Ruifen
R
Hu
Zhibin
Z
Xu
Lin
L
Huang
Xinen
X
Chen
Yijiang
Y
Tian
Tian
T
Wei
Qingyi
Q
Boffetta
Paolo
P
Shen
Hongbing
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality*; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9