RT Journal Article
SR Electronic
T1 Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 381
OP 390
DO 10.1183/09031936.00125608
VO 35
IS 2
A1 D. B. Scherf
A1 H. Dally
A1 P. Müller
A1 G. Werle-Schneider
A1 B. Jäger
A1 L. Edler
A1 S. Tuengerthal
A1 J. R. Fischer
A1 P. Drings
A1 H. Bartsch
A1 A. Risch
YR 2010
UL http://erj.ersjournals.com/content/35/2/381.abstract
AB 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.