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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, a group of new prognostic factors have been added to the list of well-known clinical prognostic factors of non-small cell lung cancer. Among these are mutations in the K-ras oncogene, abnormalities in p53, the presence of N-CAM expression as measured by Mab immunostaining and elevated serum levels of NSE. These factors have provided important clinical insights into the biology of lung cancer and prospective studies using these biomarkers are now warranted to provide further important clues about their potential significance in treatment selection of patients.
Lung Cancer 1995 Apr
PMID:Prognostic factors in NSCLC. Recent experiences. 755 31

A restriction fragment length polymorphism in codon 72 of the p53 gene has been implicated in lung cancer risk, although the functional significance of the polymorphism has not been determined. This association was examined in 109 lung cancer cases (67 African-American and 42 Mexican-American) and 114 controls (74 African-American and 40 Mexican-American) identified from a molecular epidemiological study of lung cancer. The susceptible Pro/Pro genotype was associated with a 1.56-fold higher risk of lung cancer in African-Americans and a 1.95-fold in Mexican-Americans, although neither estimate was statistically significant. In fact, the prevalence of the Pro/Pro genotype was only 2.5% in Mexican-American controls, compared with 20.3% for African-American controls. Patients with the susceptible genotype appeared to have earlier age at diagnosis and lower mean cigarette pack-year exposures than did patients with the Arg/Arg or Arg/Pro genotypes. Risk estimates for the susceptible genotype were 11.29 (1.1, 111.3) for patients < 53 years of age and 14.1 (1.5, 130.6) for patients who reported < 30 pack-years of smoking. The Pro/Pro genotype was not associated with elevated risk in older patients, nor with heavier smokers. If Pro/Pro is a susceptible genotype, the lower prevalence evident in Mexican-Americans may partly explain their lower rates of lung cancer.
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PMID:Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype. 755 76

An association between the BstU I 1-1 (Pro-Pro) genotype of the p53 codon 72 polymorphism and lung cancer has previously been reported by Kawajiri et al. A reanalysis of the data by Kawajiri et al. revealed no significant difference between patients and controls with respect to allele frequencies, and the increased frequency of BstU I 1-1 homozygotes was mostly ascribable to a deviation from the Hardy-Weinberg equilibrium. In an attempt to replicate the results by Kawajiri et al. we have studied three p53 polymorphisms (BstU I and Msp I RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotypes in Swedish lung cancer patients and controls. The results concerning the codon 72 polymorphism were largely negative. Thus there was no significant association between lung cancer and the BstU I 1-1 type, and only a marginal difference (P = 0.044) with respect to the BstU I allele frequency when lung cancer patients were compared with patients with chronic obstructive pulmonary disease (COPD). However, when the analysis was based on haplotype frequencies larger differences appeared and it was found that only BstU I 1 (pro) alleles linked to 16 bp 1 alleles were associated with lung cancer. Pro alleles linked to the 16 bp duplication appeared instead to confer some protection against cancer. Thus the codon 72 alleles need not be functionally involved in lung cancer, but may rather be markers in linkage disequilibrium with other cancer susceptibility sites on p53.
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PMID:P53 polymorphisms and haplotypes in lung cancer. 755 81

Alterations in the p53 tumor suppressor gene appear to be important in the development of many human tumors. The wild-type p53 gene has a polymorphism at codon 72 that presents the arginine (CGC) or proline (CCC) genotype, which recently has been reported to be associated with genetically determined susceptibility to smoking-related lung cancers. To determine whether this p53 genotype influences individual risk of urologic cancer and/or its progression, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to assay the allelic frequencies of this polymorphism in 85 renal cell carcinoma patients, 151 urothelial cancer patients, 33 testicular cancer patients, 28 prostatic cancer patients and 56 patients without neoplastic disease. The allelic distributions of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) in patients with renal cell carcinoma (29.4%, 55.3%, 15.3%), urothelial cancers (45.7%, 39.7%, 14.6%), testicular cancer (45.4%, 48.5%, 6.1%) or prostate cancer (42.9%, 50.0%, 7.1%) did not differ significantly from those in the normal controls. However, Pro/Pro genotype in renal cell carcinoma and urothelial cancer (smoking-related cancers) was more frequent than that in prostate cancer and testicular cancer (smoking-unrelated cancers) with borderline significance (P = 0.0881). There was no particular correlation between frequency of the three genotypes and grade or stage of each type of tumor. The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.
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PMID:Allelic frequency of p53 gene codon 72 polymorphism in urologic cancers. 755 95

A close association of smoking-associated lung cancer incidence with the Msp 1 and 1le-Val polymorphisms of CYP1A1 gene was found in a Japanese population in terms of genotype frequency comparison and cigarette dose response. A synergistic increase in susceptibility to lung cancer was observed when the susceptible genotypes of CYP1A1 were combined with a deficient GSTM1 genotype. Individual difference in expression levels of Ahr and Arnt mRNAs was observed, and the expression levels of CYP1A1 appeared to associate with those of transcriptional factors. The Ahr protein has two different structures, ascribed to one amino acid replacement at codon 554 of Arg by Lys. However, this germ line polymorphism did not show a significant association with AHH inducibility nor lung cancer incidence. The p53 gene alterations in lung cancer tissues were more frequently observed among the patients with a susceptible allele of CYP1A1 gene.
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PMID:Genetic polymorphisms of drug-metabolizing enzymes and lung cancer susceptibility. 758 93

The p53 alteration is the most common alteration found in human cancer. It usually involves missense mutations that stabilize the p53 protein, which in turn accumulates, reaching levels detectable by immunohistochemistry. We and others have demonstrated that this overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. This result was assessed by the presence of p53 antibodies in sera of patients with various types of cancers, whereas normal populations do not exhibit such antibodies. In lung cancer, the prevalence of p53 antibodies is high (30%) and is correlated with a very high rate of p53 mutations in this cancer (60-70%). We show that these antibodies are always present at the time of diagnosis, but never appear during tumour development, an observation strengthened by the fact that these antibodies are mostly IgG, corresponding to a secondary immune response. These results suggest that the humoral response is an early event and that p53 antibodies can be used as a precocious marker of p53 alteration before clinical manifestation of the disease.
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PMID:Serum p53 antibodies as early markers of lung cancer. 758 54

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies to search for risk factors in carcinogenic events. The lung cancer incidence for females in Hong Kong is unusually high, ranking among the highest in the world despite a low percentage with a history of smoking. To gain insights into possible etiological risk factors responsible for this high incidence, we examined p53 mutations in 35 lung cancer specimens from Chinese females living in Hong Kong and compared them with 35 matched cases from Japanese women as well as previously reported p53 mutations in the world literature. p53 mutations in exons 5-8 were present in 20 and 31% of the Hong Kong and Japanese cases, respectively. Notably, single-base deletions within runs of identical bases were observed in 3 (43%) of the 7 mutations in the Hong Kong cases, in contrast to the absence of such mutations in the controls and the extreme scarcity in the literature, suggesting that distinct environmental and/or genetic factor(s) might be involved. Although the frequent occurrence of characteristic single-base deletions could be a reflection of mutator mutations leading to inefficient mismatch repair of slipped strand mispairings, none of the lung cancer specimens exhibited such microsatellite instabilities.
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PMID:Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women in Hong Kong. 758

Mutations of the p53 tumor suppressor gene are the most common molecular genetic abnormality to be described in ovarian cancer. To determine the feasibility of mutant p53 as a molecular target for gene therapy in ovarian cancer, we constructed an adenovirus vector containing the wild-type p53 gene. The ability of this adenovirus construct (Ad-CMV-p53) to express p53 protein was examined by Western blot analysis in the H358 lung cancer cell line, which has a homozygous deletion of the p53 gene. The ability of the adenovirus vector system to infect ovarian cancer cells was tested using an adenovirus containing the beta-galactosidase reporter gene under the control of the CMV promoter (Ad-CMV-beta gal). The ovarian cancer cell line 2774, which contains an Arg273His p53 mutation, was infected with Ad-CMV-beta gal, and the infected cells were assayed for beta-galactosidase activity after 24 hr. To test the ability of wild-type p53 to inhibit cell growth, the 2774 cell line was infected with Ad-CMV-p53 or Ad-CMV-beta gal, and the effect of these agents on the growth of 2774 cells was determined using an in vitro growth inhibition assay. Western blot analysis of lysates from H358 cells infected with Ad-CMV-p53 showed expression of wild-type p53 protein. When 2774 cells were infected with Ad-CMV-beta gal at a multiplicity of infection (m.o.i.) of 10 PFU/cell, > 90% of cells showed beta-galactosidase activity, demonstrating that these cells are capable of efficient infection by the adenovirus vector. Growth of 2774 cells infected with Ad-CMV-p53 was inhibited by > 90% compared to noninfected cells. The ability of the adenovirus vector to mediate high-level expression of infected genes and the inhibitory effect of Ad-CMV-p53 on the 2774 cell line suggests that the Ad-CMV-p53 could be further developed into a therapeutic agent for ovarian cancer.
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PMID:Adenovirus-based p53 gene therapy in ovarian cancer. 759 Apr 66

We examined replication error (RER) and loss of heterozygosity (LOH) in the region of microsatellites in 60 cases of resected lung cancer. We used microsatellite probes for the short arm of the 2nd chromosome (D2S123, D2S136), the short arm of the 3rd chromosome (D3S1067), and the short arm of the 17th chromosome (TP53). According to stage, the frequency of LOH was 25% in stage I, 33% in stage II, 44% in stage IIIA, 11% in stage III B, and 63% in stage IV. According to histological classification, the frequency of LOH was 41% for squamous cell carcinoma, 24% for adenocarcinoma, and 100% for small cell carcinoma. According to microsatellite probe results, the frequency of LOH was 6.7% for D2S123, 5.0% for D2S136, 16.7% for D3S1067, and 18.3% for TP53. Two of the 60 cases showed RER. One case was stage I squamous cell carcinoma, and the other was stage IV adenocarcinoma. Except for stage III B,LOH in the microsatellite region increases with the stage. LOH is often detected in the order of small cell carcinoma, squamous cell carcinoma, and adenocarcinoma. According to the chromosome number, LOH is detected more often in the 3rd and 17th chromosomes than in the 2nd chromosome. In 20 cases with LOH, only two showed DNA diploidy. Compared to LOH of the microsatellite region, DNA content analysis by flow cytometry has accuracy problems.
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PMID:[Detection of loss of heterozygosity by microsatellite probe and DNA content analysis]. 761 81

To study the relation between p53 mutation and metastasis in primary lung cancer, 29 pairs of primary and metastatic tumors obtained by autopsy were analyzed for abnormalities of the p53 gene, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). The tumors consisted of 6 small cell carcinomas, 13 adenocarcinomas, 8 squamous cell carcinomas, 1 large cell carcinoma, and 1 adeno-squamous cell carcinoma. PCR-SSCP analysis showed that 3 small cell carcinomas (50%), 3 adenocarcinomas (23%), 2 squamous cell carcinomas (25%), and 1 large cell carcinoma (100%) had p53 gene mutations. The abnormalities were found between exons five and eight. The metastatic tumor and the primary tumor had similar mutations. These results suggest that p53 gene mutation may occur before distant metastasis and may be stable during the process of metastasis.
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PMID:[p53 gene abnormalities in advanced primary lung cancer and metastatic tumors]. 761 96


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