Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis.
The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.
Scherf
D B
DB
Dept of Epigenomics and Cancer Risk Factors, German Cancer Research Center Heidelberg, Germany.
Dally
H
H
Müller
P
P
Werle-Schneider
G
G
Jäger
B
B
Edler
L
L
Tuengerthal
S
S
Fischer
J R
JR
Drings
P
P
Bartsch
H
H
Risch
A
A
D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000494:pharmacology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
D000970:Antineoplastic Agents; D020778:Matrix Metalloproteinase 2