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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-11-10
pubmed:abstractText
The expression of selected gene products involved in cell differentiation and cell growth and genetic polymorphism of detoxifying genes was examined in 105 surgically resected nonsmall cell lung cancer (NSCLC) patients, and the relationship of these factors was correlated with cigarette smoking and patient survival. Genotyping of peripheral blood lymphocytes from 87 patients was performed for CYP2E1, GSTM1, GSTT1, mEH, and MPO detoxifying genes using polymerase chain reaction. Formalin-fixed, paraffin-embedded tissue was immunostained with antibodies to p53, p27, phospho-AKT, and bcl-2 using the avidin-biotin-peroxidase method and tissue microarray technique. Tumors were assigned a positive or negative score based on more than 10% of tumor cells staining positive with the antibody. The subtypes of NSCLC included 48 adenocarcinomas, 47 squamous cell carcinomas, and 10 large cell undifferentiated carcinomas. A total of 54 tumors were pathologic stage I, 23 were stage II, and 26 were stage III. All subjects smoked (range, 10-175 pack-years; mean, 60 pack-years). The mean overall survival was 112 weeks (median, 129 weeks). Patients with p53-positive tumors had significantly fewer pack-years of smoking (52 pack-years vs 72 pack-years; P = 0.021), smoked fewer years (34 years vs 40 years; P = 0.018), and had significantly better survival compared with those with p53-negative tumors (P = 0.045). When smoking history was further analyzed, the authors found that p53 expression was associated with the number of years smoked and not the number of packs smoked per day. Patients with squamous cell carcinoma had smoked longer compared with those with adenocarcinoma (P = 0.011). Significant association was seen between the CYP2E1 wild-type allele and better survival (P = 0.016). Patients with stage I tumors had better survival compared with stages II and III (P = 0.032). No association was found between survival and tumor type; tumor differentiation; expression of phospho-AKT, p27, and bcl-2; and polymorphic metabolizing genes other than CYP2E1. The significant association of long duration of smoking (>40 years) with loss of p53 expression and poor survival suggests inactivation of the protective p53 pathway in those who had a history of more than 40 years of smoking.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1541-2016
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
315-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15536330-Adult, pubmed-meshheading:15536330-Aged, pubmed-meshheading:15536330-Aged, 80 and over, pubmed-meshheading:15536330-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:15536330-Cell Cycle, pubmed-meshheading:15536330-Cell Nucleus, pubmed-meshheading:15536330-Cytochrome P-450 CYP2E1, pubmed-meshheading:15536330-Female, pubmed-meshheading:15536330-Follow-Up Studies, pubmed-meshheading:15536330-Humans, pubmed-meshheading:15536330-Lung, pubmed-meshheading:15536330-Lung Neoplasms, pubmed-meshheading:15536330-Male, pubmed-meshheading:15536330-Middle Aged, pubmed-meshheading:15536330-Neoplasm Staging, pubmed-meshheading:15536330-Polymorphism, Genetic, pubmed-meshheading:15536330-Prognosis, pubmed-meshheading:15536330-Proliferating Cell Nuclear Antigen, pubmed-meshheading:15536330-Protein-Serine-Threonine Kinases, pubmed-meshheading:15536330-Proto-Oncogene Proteins, pubmed-meshheading:15536330-Proto-Oncogene Proteins c-akt, pubmed-meshheading:15536330-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:15536330-Smoking, pubmed-meshheading:15536330-Tumor Suppressor Protein p53
pubmed:year
2004
pubmed:articleTitle
CYP2E1 polymorphism, cigarette smoking, p53 expression, and survival in non-small cell lung cancer: a long term follow-up study.
pubmed:affiliation
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. ahaque@utmb.edu
pubmed:publicationType
Journal Article