A specific member of the cytochrome P450 superfamily of enzymes, designated P450IA (including 2 isozymes, P450IA1 and P450IA2), which is involved in the metabolic activation of polycyclic aromatic hydrocarbons and aromatic amines, was studied in lung tissue from 25 lung cancer patients by immunohistochemistry. The pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), from the same patients was also measured. Cytochrome P450IA was localized principally in the peripheral airways in alveolar epithelium of types I and II and in ciliated columnar and cuboidal bronchiolar epithelium. The amount of P450IA in the bronchial wall was minimal and was localized mainly in the capillary endothelium and the epithelium of the bronchial glands. Smoking was the most important factor related to the presence of P450IA and the AHH activity in lung tissue. None of the 10 ex-smokers, but all except I of the current smokers had detectable level of P450IA. The localization of the cancer was also correlated with the presence of cytochrome P450IA. Peripheral lung tissue stained positively in all patients with a peripheral adenocarcinoma who currently smoked (8/8) but in less than half of those with a bronchial cancer who were smokers (3/7). Our data suggest that the smokers who have an inducible cytochrome P450IA are especially at increased risk of developing lung cancer of the peripheral adenocarcinomatous type.
We investigated point mutational DraI and RsaI restriction fragment length polymorphisms (RFLPs) in the CYP2E1 gene in 101 lung cancer patients, 40 patients with other pulmonary diseases and 121 healthy control subjects. In the DraI RFLP analysis of the 121 healthy control subjects, 96 had the DD genotype, 24 the CD genotype and one the CC genotype. Genotypic distribution in the patients with other pulmonary disease showed a similar trend (P = 0.50), though the group was considerably smaller. The distribution of DraI genotypes in the lung cancer patients was not significantly different from that of the healthy controls (P = 0.44). We were not able to reproduce the results of a Japanese report describing a statistically significant association between the rare DraI RFLP genotype CC and predisposition to lung cancer. Furthermore, this genotype was much less frequent in our study populations than in the Japanese study. The other point mutation studied, which results in RsaI restriction site polymorphism in the 5'-flanking region of the CYP2E1 gene, was almost absent in our study groups. These findings on our Finnish lung cancer population suggest that the CYP2E1 gene polymorphisms studied do not have an important role in susceptibility to lung cancer.
Early Colorectal Neoplastic LesionsThe Adenoma-Carcinoma SequenceMost cases of colorectal (CR) cancer are sporadic; a small percentage occur in heritable syndromes such as familial adenomatous polyposis (FAP), attenuated adenomatous polyposis coli, flat adenoma syndrome, hereditary nonpolyposis CR cancer (HNPCC), juvenile polyposis syndromes, Peutz-Jeghers syndrome and hereditary non-FAP, non-HNPCC.A large body of clinical evidence supports the belief that a majority of CR cancers arise from precursor lesions, benign adenomatous polyps [1]. The classical adenoma-carcinoma sequence postulates that adenomas contain dysplastic epithelium which arises from mutations in either the adenomatous polyposis coli gene (APC) or the DNA mismatch repair genes.There is some confusion in the use of the terms dysplasia and adenoma: in the West, protruded or slightly elevated noninvasive neoplastic lesions are called adenomas, while flat or depressed neoplastic noninvasive lesions are called dysplasia. In the East, both types of lesions are called adenomas and described as protruding, flat or depressed. There is now a trend to use the terms polypoid and nonpolypoid. Polypoid adenomas correspond to protruded polyps, including both sessile and pedunculated types. Nonpolypoid adenomas include sligthly elevated polyps and the flat or depressed areas of dysplasia (or adenoma).In polypoid adenomas, the risk of malignant transformation increases over time and with size and/or villous architecture. In populations with a high prevalence of adenomas, 40 to 50 % of individuals have multiple lesions. The degree of dysplasia is greater in patients with multiple rather than with solitary adenomas, which may explain the higher risk for cancer in patients with multiple adenomas. De Novo CancerThe term ªde novoº cancer was initially introduced to describe those CR cancers which did not develop from a preexisting adenoma, along the adenoma±carcinoma sequence. In Japan, the concept of ªflat or depressed adenomaº was elaborated by Muto in 1985, and increasing numbers of nonpolypoid cancers (mainly early cancers) have since been reported in that country [2]. The macroscopic morphology of CR adenomas is determined by the balance between proliferation and apoptosis; the high apoptosis found in depressed adenomas correlates with low net growth [3]. In depressed adenomas, the tubular architectural pattern is distinct and the villous architectural pattern is nonexistent. These lesions were originally thought to be unique to the Japanese population. A prospective study of 1000 colonoscopies in the UK revealed that 36 % (117/ 321) of the adenomas found were nonpolypoid and that the likelihood of high-grade dysplasia or cancer increased from 4 % (3/70) in small nonpolypoid lesions, to 6 % (9/ 154) in small protruded polyps, 16 % (8/50) in larger polyps, 29 % (14/49) in large nonpolypoid lesions, and 75 % (3/4) in nonpolypoid depressed lesions [4]. These Western data corroborate the notion expressed by Kudo et al. that although depressed lesions have a low fre...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.