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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several rodent studies based on molecular biology have suggested that accumulation of genetic alterations in cancer-associated genes is required to convert a normal cell into a malignant cell. Activation of oncogenes and inactivation of tumor suppressor genes appear to be involved in carcinogenesis. In renal cell carcinomas, we have recently implied that the presence of tumor suppressor genes at chromosome 3p13-14.3 and 21.3, the regions where are also commonly deleted in adenocarcinoma of the lung; at chromosome 5q21, the region where the MCC (mutated in colorectal cancer) gene and APC (adenomatous polyposis coli) gene are located; at chromosome 6q27; and at 10q 21-23. We have also indicated that genes on 3p is probably important for development of RCCs and genes on 5q, 6q, and 10q may be associated with progression of RCCs.
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PMID:[Tumor suppressor genes associated with development of human renal cell carcinoma]. 149 60

In mammals, the cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) are a supergene family comprised of four multigene families, named alpha, mu, pi and theta. In man, within the mu class gene family there is a gene (the GSTmu 1 locus) that is polymorphic and is only expressed in 50-55% of individuals. It has previously been reported, using trans-stilbene oxide (tSBO) as a specific substrate for the expressed phenotype, that smokers with the null phenotype had a greater susceptibility to lung cancer. In a subsequent study, it was shown that on Southern blot analyses of human DNAs using a GSTmu 1 cDNA probe a DNA fragment was absent in certain individuals. The absence of this band correlated with the tSBO null phenotype. In the present work, DNA clones derived from GST mu class genomic sequences were used as probes in Southern blot analyses and confirmed the correlation between the lack of a DNA fragment and the null phenotype; moreover in this case, using radioimmunoassay for the GST mu protein, these probes were then used in a genotyping assay to investigate further the association of GSTmu 1 polymorphism with susceptibility to lung cancer. It was found that in a control group of 225 individuals, of unknown smoking history, 42% lacked the restriction fragment and were homozygous null, and therefore 58% were either heterozygous or were homozygous normal. Among 228 lung cancer patients, which included all tumour types, a similar distribution occurred, namely 43% were homozygous and 57% were heterozygous or homozygous normal. If, however, the tumours were analysed by tumour type a small but significant positive correlation with the homozygous null genotype was seen in squamous carcinoma of the lung, and an apparently negative correlation with adenocarcinoma of the lung.
Carcinogenesis 1991 Sep
PMID:Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. 168 31

Recently, i(8q) was suggested to be a nonrandom chromosomal abnormality characteristic of adenocarcinoma of the lung. To further investigate this observation, a chromosomal analysis of five cases of pleural effusions representing metastatic adenocarcinoma from different primary sites (two lung, two breast, and one stomach) was undertaken. The i(8q) occurred in three of the tumors, one from each of the three different primary sites. In addition, abnormalities of the short arm of chromosome 3 and extra copies of chromosome 7, both of which have been associated with adenocarcinoma of the lung, were simultaneously present in the same three tumors. Our findings demonstrate that i(8q) is not specific for adenocarcinoma of the lung and that it may have a role in the pathogenesis of adenocarcinomas from multiple organs. The simultaneous presence of i(8q), abnormalities of 3p, and extra copies of chromosome 7 may indicate a relationship among these abnormalities in multistep carcinogenesis or the development of metastatic potential.
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PMID:Cytogenetic abnormalities common to adenocarcinoma metastatic to the pleura. 275 74

We have previously reported on an association of genetic susceptibility to squamous cell carcinoma of the lung with two polymorphisms of the CYP1A1 gene, an MspI polymorphism and an isoleucine-valine (Ile-Val) polymorphism. We report here that the two CYP1A1 polymorphisms were associated with current or ex-smokers with adenocarcinoma of the lung. We first compared smoking status of the patients by differentiation grades of adenocarcinoma. Proportion of current or ex-smokers and their cigarette consumption was the highest among the poorly differentiated. Second, the two polymorphisms of CYP1A1 were examined among current or ex-smokers with three differentiation grades, and we found that poorly differentiated adenocarcinoma showed significantly high frequencies of genotypes C and Val/Val, which have been found to be 'susceptible' in squamous cell carcinoma of the lung. Third, a case-control study was carried out to estimate the genetic risk for CYP1A1 genotypes to differentiation grades, selecting only current or ex-smokers in patients and controls. Current or ex-smokers with 'susceptible' genotype C or Val/Val were at significant risk, with an odds ratio of 3.25 or 3.22 (95% confidence interval (CI), 1.40-7.56 or 1.00-10.32) for adenocarcinoma as a whole, respectively. The odds ratio increased to 4.51 or 4.09 (95% CI, 1.73-11.78 or 1.12-14.91) for poorly differentiated, while the odds ratios for other differentiated grades were not significant. Finally, a relation of the genetic risk to cigarette dose levels was evaluated.
Carcinogenesis 1995 Sep
PMID:Association of cigarette smoking and CYP1A1 polymorphisms with adenocarcinoma of the lung by grades of differentiation. 755 77

Histological examination revealed that many peripheral type papillary adenocarcinomas appear to develop from atypical adenomatous hyperplasia (AAH), which can be called adenoma or in situ adenocarcinoma, and progress stepwise. Molecular-biologically, loss of heterozygosities of 3, 11 and 17 chromosomes, point mutation of ras oncogene and p53 anti-oncogene, amplification of myc oncogene, and overexpression of erbB2 oncogene are related to lung cancer development. Especially, ras and p53 gene abnormalities are closely associated with poor prognosis of lung adenocarcinoma. Future molecular-biological examinations should focus on AAH and/or early stage adenocarcinoma of the lung, in order to clarify the gene abnormality at the early stage of lung carcinogenesis.
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PMID:[Advances in pathobiological research on lung carcinoma]. 797 12

We analyzed the presence or absence of K-ras mutations in sputum samples with atypical cells by colony hybridization. The frequency of K-ras mutations in 104 patients with adenocarcinoma of the lung was also examined using dot blotting. No mutations in K-ras codon 12 were detected in the 12 sputum samples examined, which included three specimens from patients who later developed lung adenocarcinoma. Because of the paucity of sputum samples, it was difficult to conclude whether K-ras gene mutations are useful for molecular screening for lung cancer at the present time. Secondly, we detected 12 cases [12%; 10 males (19%) and two females (4%)] with a K-ras mutation among 104 patients with lung adenocarcinoma. Although the smoking rate of patients (89%) was higher than the general Japanese male population (approximately 60%), indicating that smoking may be related to the occurrence of adenocarcinoma of the lung, it was unclear whether smoking was related to K-ras mutation from our results. Other factors may contribute to K-ras mutation.
Carcinogenesis 1996 Aug
PMID:K-ras gene mutation in sputum samples containing atypical cells and adenocarcinoma cells in the lung. 876 26

This study examined the effects of 6-phenylhexyl isothiocyanate (PHITC) on lung tumorigenesis in F344 rats induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Two biomarkers of NNK metabolism, 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing hemoglobin adducts and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc) in urine, were also quantified during the course of the tumor induction experiment. Rats were divided into groups as follows: (1) NNK, 2 p.p.m. in drinking water, 60 rats; (2) NNK, 2 p.p.m. in drinking water and PHITC, 1 micromol/g NIH-07 diet, 60 rats; (3) PHITC, 1 micromol/g NIH-07 diet, 20 rats; (4) control, 20 rats. PHITC was added to the diet for 1 week prior to and during 111 weeks of NNK treatment. There were no effects of PHITC on body weight, mortality, blood chemistry or hematology. Seventy percent of the rats treated with NNK had adenoma or adenocarcinoma of the lung. In the rats treated with NNK plus PHITC, the total percent incidence of lung tumors was 26% (P < 0.01 compared with NNK). PHITC had no effect on the total incidence of exocrine pancreatic tumors induced by NNK. The rats treated with PHITC and NNK had significantly lower levels of HPB-releasing hemoglobin adducts throughout the course of the bioassay than did those treated with NNK alone and significantly higher levels of NNAL plus NNAL-Gluc excreted in urine at two time points during the bioassay. These results demonstrate that near lifetime administration of PHITC to rats strongly inhibits the metabolic activation and lung tumorigenicity of NNK.
Carcinogenesis 1996 Sep
PMID:Inhibitory effects of 6-phenylhexyl isothiocyanate on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolic activation and lung tumorigenesis in rats. 882 35

To examine whether dietary sugar modifies lung cancer risk, a case-control study involving 463 cases with lung cancer and 465 hospitalized controls was conducted in Uruguay in the period 1993-1996. Dietary patterns were assessed in detail using a 64-item food-frequency questionnaire, which allowed the calculation of total energy intake. After adjustment for potential confounders through a model that included tobacco smoking and total energy, total fat, vitamin C, and alpha-carotene intakes, an increased risk for sugar-rich foods, total sucrose intake, sucrose to dietary fiber ratio, and glycemic index for lung cancer was observed (odds ratio for highest category of total sucrose intake = 1.55, 95% confidence interval = 0.99-2.44). When lung cancer was analyzed separately by cell type, odds ratios for small cell and large cell undifferentiated carcinoma were higher than those observed for squamous cell and adenocarcinoma of the lung. The joint effect of pack-years, total fat intake, and sucrose intake was associated with an increased risk of 28.3 (95% confidence interval = 13.4-59.7) for high values of the three variables. The study suggests that high sucrose intake could be an important risk factor in lung carcinogenesis. Further studies, both epidemiological and experimental, are needed to replicate the present findings and to clarify the mechanism(s) of sucrose intake in lung carcinogenesis.
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PMID:Dietary sugar and lung cancer: a case-control study in Uruguay. 977 Jul 25

Plant sterols are substances present in vegetable oils, corn and some fruits. According to previous studies, phytosterols are protective in colon carcinogenesis. This case-control study was carried out in order to establish a possible protective role of plant sterols in lung carcinogenesis. The study was performed in Montevideo, Uruguay, during 1993-1996, and included 463 cases with lung cancer and 465 hospitalized controls. Total plant sterol intake was associated with a reduction in risk of 50% when contrasting the upper exposure quartile with the lower, after controlling for major confounders, including tobacco smoking and total energy intake. This protective effect was specially evident in adenocarcinoma of the lung (OR 0.29, 95% CI 0.14-0.63). Therefore, plant sterol intake appears to be an important variable in lung carcinogenesis. Further studies are needed in order to replicate the present findings.
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PMID:Phytosterols and risk of lung cancer: a case-control study in Uruguay. 979 52

Environmental carcinogen exposure is requisite for the development of nearly all lung cancer, and it is well known that asbestos exposure interacts synergistically with tobacco smoke to induce lung cancer. However, the precise molecular lesions induced by asbestos are unknown. Furthermore, it is also unknown whether asbestos carcinogenesis proceeds in a fashion independent of or dependent upon the induction of fibrosis in workers with high asbestos exposures. Previous studies have suggested that asbestos is associated with the presence of a k-ras mutation in adenocarcinoma of the lung. We aimed to test whether occupational asbestos exposure was associated with k-ras codon 12 mutations in lung adenocarcinoma tumors and to determine whether this was conditional on the presence of asbestosis. All newly diagnosed, resectable lung cancer patients receiving treatment at the Massachusetts General Hospital between November 1992 and December 1996 were eligible to participate. Because k-ras mutation is very strongly associated with adenocarcinoma, and men were more likely to be occupationally exposed to asbestos, the study was restricted to males with this histological diagnosis. There were 84 male patients with available questionnaire-derived work history data and paraffin-embedded tumor tissue for determination of k-ras mutation status. Chest radiographic evaluation was done for all of the patients who reported occupational exposure to asbestos. The prevalence of k-ras mutation was higher among those with a history of occupational asbestos exposure (crude odds ratio, 4.8; 95% confidence interval, 1.5-15.4) compared to those without asbestos exposure, and this association remained after adjustment for age and pack-years smoked (adjusted odds ratio, 6.9; 95% confidence interval, 1.7-28.6). An index score that weights both the dates of exposure and the estimated intensity of exposure indicated that those with k-ras mutations had significantly greater asbestos exposures than those without mutations (P < 0.01). Analysis of the descriptive components of exposure indicated that the duration of exposure was not associated with k-ras mutation, but that the time since initial exposure was significantly associated with mutation status. The association of k-ras mutation and reported asbestos exposure was not dependent on the presence of radiographic evidence of asbestos-related disease. These data suggest that asbestos exposure increases the likelihood of mutation at k-ras codon 12 and that this process occurs independently of the induction of interstitial fibrosis.
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PMID:k-ras mutation and occupational asbestos exposure in lung adenocarcinoma: asbestos-related cancer without asbestosis. 1049 9


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