title: VCP gene variation predicts outcome of advanced non-small-cell lung cancer platinum-based chemotherapy.
abstract: Valosin-containing protein (VCP), or p97, is a member of the ATP-binding protein family, and is involved in numerous cellular events, such as, protein degradation, membrane fusion, and chaperone activity. VCP has been demonstrated playing a critical role in non-small-cell lung cancer (NSCLC) pathogenesis and progression recently. We investigated the association between VCP polymorphisms and clinical outcome in advanced NSCLC patients undergoing platinum-based chemotherapy. We recruited 663 Chinese advanced NSCLC patients who were treated with platinum-based regimens, and using their clinical data, we assessed the efficacy and side effects of their treatment. Three tag-single nucleotide polymorphisms (SNPs) of VCP were genotyped. SNP rs2074549 showed a significant association with severe neutropenia. Its G/G genotype increased the risk of grade 3 or 4 neutropenia compared with wild-type homozygotes A/A (P = .001, odds ratio = 2.975). Haplotype association analysis revealed that CGA was associated with the increased incidence of severe neutropenia (P = .041, odds ratio = 1.439). However, no significant relationship was found between the presence of VCP polymorphisms and treatment efficacy when objective response, progression-free survival, and overall survival (OS) were evaluated. Our study is the first to provide evidence that VCP polymorphisms are associated with a severe chemotherapy-related adverse outcome in platinum-treated advanced NSCLC patients.
authors: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, China.
authors: J
authors: J
authors: Peng
authors: L X
authors: LX
authors: Yang
authors: X Y
authors: XY
authors: Zhao
authors: Z Q
authors: ZQ
authors: Gao
authors: J
authors: J
authors: Yang
authors: W T
authors: WT
authors: Wu
authors: H J
authors: HJ
authors: Wang
authors: J C
authors: JC
authors: Wang
authors: J
authors: J
authors: Qian
authors: H Y
authors: HY
authors: Chen
authors: L
authors: L
authors: Jin
authors: C X
authors: CX
authors: Bai
authors: B H
authors: BH
authors: Han
authors: W M
authors: WM
authors: Wang
authors: D R
authors: DR
authors: Lu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D018797:Cell Cycle Proteins / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D000074405:Valosin Containing Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009944:Organoplatinum Compounds; D004247:DNA; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein