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Matrix metalloproteinase‐2 polymorphisms and clinical outcome of Chinese patients with nonsmall cell lung cancer treated with first‐line, platinum‐based chemotherapy
Author(s) -
Zhao Xueying,
Wang Xun,
Wu Wenting,
Gao Zhiqiang,
Wu Junjie,
Garfield David H.,
Wang Haijian,
Wang Jiucun,
Qian Ji,
Li Huan,
Jin Li,
Li Qiang,
Han Baohui,
Lu Daru,
Bai Chunxue
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26669
Subject(s) - medicine , lung cancer , oncology , chemotherapy , matrix metalloproteinase
BACKGROUND: Matrix metalloproteinase‐2 ( MMP‐2 ) is well known for its critical role in cell survival and cancer development. It also plays an important role in hematopoietic recovery after chemotherapy‐induced myelosuppression. In this study, the authors investigated the association of MMP‐2 polymorphisms with treatment efficacy and the occurrence of severe toxicity in patients with nonsmall cell lung cancer (NSCLC) who were receiving first‐line, platinum‐based chemotherapy. METHODS: A pharmacogenetic association study was performed in 663 Chinese patients who had inoperable stage III/IV NSCLC and were receiving first‐line, platinum‐based regimens. Information about objective response, progression‐free survival, overall survival, grade 3 or 4 gastrointestinal toxicity (nausea/vomiting), and hematologic toxicity (neutropenia, anemia, thrombocytopenia) was available. Sixteen tag single nucleotide polymorphisms (SNPs) of MMP‐2 were assessed. RESULTS: In 7 polymorphisms, significant associations were observed with the incidence of grade 3 or 4 neutropenia. The variant homozygotes of reference SNP rs12934241 exhibited the most significant effect on the risk of neutropenia, leading to an incidence rate that increased from 12.3% (for the C/C genotype) to 50% (for the T/T genotype; odds ratio, 8.33; P = 8.8 × 10 −5 ). Stratified analyses indicated that rs12934241 exhibited a much stronger influence in the cisplatin‐gemcitabine regimen subgroup than subgroups that received other regimens ( P interaction = .003). Further haplotype analyses produced results that were consistent with results from single‐SNP analyses. However, no significant association was observed between MMP‐2 polymorphisms and treatment efficacy, including response rate, clinical benefit, progression‐free survival, and overall survival. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence for a predictive role of MMP‐2 polymorphisms in the variability of severe chemotherapy‐related neutropenia among Chinese patients with platinum‐treated, advanced NSCLC. Cancer 2012;3587–3598. © 2011 American Cancer Society.