title: Matrix metalloproteinase-2 polymorphisms and clinical outcome of Chinese patients with nonsmall cell lung cancer treated with first-line, platinum-based chemotherapy.
abstract: 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.
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhao
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Gao
authors.forename: Junjie
authors.initials: J
authors.lastname: Wu
authors.forename: David H
authors.initials: DH
authors.lastname: Garfield
authors.forename: Haijian
authors.initials: H
authors.lastname: Wang
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D016190:Carboplatin; D020778:Matrix Metalloproteinase 2; D002945:Cisplatin