{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:29:17Z","timestamp":1762176557206,"version":"build-2065373602"},"reference-count":46,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2011,11,9]],"date-time":"2011-11-09T00:00:00Z","timestamp":1320796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Matrix metalloproteinase\u20102 (<jats:italic>MMP\u20102<\/jats:italic>) is well known for its critical role in cell survival and cancer development. It also plays an important role in hematopoietic recovery after chemotherapy\u2010induced myelosuppression. In this study, the authors investigated the association of <jats:italic>MMP\u20102<\/jats:italic> polymorphisms with treatment efficacy and the occurrence of severe toxicity in patients with nonsmall cell lung cancer (NSCLC) who were receiving first\u2010line, platinum\u2010based chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>A pharmacogenetic association study was performed in 663 Chinese patients who had inoperable stage III\/IV NSCLC and were receiving first\u2010line, platinum\u2010based regimens. Information about objective response, progression\u2010free 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 <jats:italic>MMP\u20102<\/jats:italic> were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>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; <jats:italic>P<\/jats:italic> = 8.8 \u00d7 10<jats:sup>\u22125<\/jats:sup>). Stratified analyses indicated that rs12934241 exhibited a much stronger influence in the cisplatin\u2010gemcitabine regimen subgroup than subgroups that received other regimens (<jats:italic>P<\/jats:italic><jats:sub>interaction<\/jats:sub> = .003). Further haplotype analyses produced results that were consistent with results from single\u2010SNP analyses. However, no significant association was observed between <jats:italic>MMP\u20102<\/jats:italic> polymorphisms and treatment efficacy, including response rate, clinical benefit, progression\u2010free survival, and overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>To the authors' knowledge, this study provides the first evidence for a predictive role of <jats:italic>MMP\u20102<\/jats:italic> polymorphisms in the variability of severe chemotherapy\u2010related neutropenia among Chinese patients with platinum\u2010treated, advanced NSCLC. Cancer 2012;3587\u20133598. \u00a9 2011 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.26669","type":"journal-article","created":{"date-parts":[[2011,11,9]],"date-time":"2011-11-09T12:32:05Z","timestamp":1320841925000},"page":"3587-3598","source":"Crossref","is-referenced-by-count":11,"title":["Matrix metalloproteinase\u20102 polymorphisms and clinical outcome of Chinese patients with nonsmall cell lung cancer treated with first\u2010line, platinum\u2010based 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