Journal of the National Cancer Institute

Our medical research library holds 32 studies published in Journal of the National Cancer Institute (1973–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 16 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 8 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Oxford University Press
• Published: 1940 to the present, United States
• Language: English
• ISSN: 0027-8874 (print), 1460-2105 (electronic)
• Absorbed: Cancer Treatment Reports
• Its record in the NLM Catalog

2020s

• Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study). J. Schüz, E. Kovalevskiy, A. Olsson, et al. 2024;116(6):866-875. PubMed · Publisher · Free full text

  Abstract

  Background: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.

  Methods: This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.

  Results: A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.

  Conclusion: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

  © The Author(s) 2024. Published by Oxford University Press.

2010s

• Quantitative Clinical Staging for Patients With Malignant Pleural Mesothelioma. R.R. Gill, B.Y. Yeap, R. Bueno, et al. 2018;110(3):258-264. Randomized trial PubMed · Publisher · Free full text

  Abstract

  Background: Analysis of the International Association for the Study of Lung Cancer (IASLC) Malignant Pleural Mesothelioma (MPM) database revealed that clinical (cTNM) staging minimally stratified survival and was discrepant with pathological (pTNM) staging. To improve prognostic classification of MPM, alternative staging models based on quantitative parameters were explored.

  Methods: An institutional review board-approved MPM registry was queried to identify patients with available pathological and preoperative imaging data. Qualifying patients were randomly assigned to training and test sets in a 1:2 ratio. Computed cTNM and pTNM staging (AJCC Cancer Staging Manual, 7th ed.) were compared. Quantitative image analysis included tumor volume assessed from three-dimensional reconstruction of computed tomography scans (VolCT) and maximal fissural thickness (Fmax). Survival was estimated using the Kaplan-Meier method, and the relationship with VolCT was examined by Cox regression analysis to identify optimized cut-points. Performance of cTNM and quantitative models derived was compared in the test set using Harrell's C index.

  Results: A total of 472 patients met inclusion criteria. TNM staging was concordant with pathological TNM staging in 171 of 472 (36.2%), understaged in 209 (44.2%), and overstaged in 92 (19.4%) patients. The most concordant feature was involvement of interlobar fissures. A quantitative clinical staging model comprising VolCT and Fmax (c-index = 0.638, 95% confidence interval [CI] = 0.603 to 0.673) performed statistically significantly better as a prognostic classifier when compared in the test set with cTNM (c-index = 0.562, 95% CI = 0.525 to 0.599, P = .001).

  Conclusions: Improved prognostic performance may be achievable by quantitative clinical staging combining VolCT and Fmax, providing a cost-effective and clinically relevant surrogate for clinical TNM stage.

• Detection of mesothioloma remains a conundrum. R. Kratzke. 2013;105(4):254-5. Editorial · Comment PubMed · Publisher

• Pleural plaques and the risk of pleural mesothelioma. J.C. Pairon, F. Laurent, M. Rinaldo, et al. 2013;105(4):293-301. PubMed · Publisher

  Abstract

  Background: The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers.

  Methods: Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided.

  Results: A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos).

  Conclusion: The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

• Researchers explore possible link between mesothelioma and dust emissions in southern Nevada. L.H. O'Hanlon. 2013;105(5):312-4. News PubMed · Publisher

2000s

• In Australia, patients and government at odds over mesothelioma treatment costs. V. Burkitt. 2007;99(23):1750-2. News PubMed · Publisher

• StatBite: Mesothelioma incidence among U.S. men. 2007;99(23):1751. PubMed · Publisher

• The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. G.E. Goodman, M.D. Thornquist, J. Balmes, et al. 2004;96(23):1743-50. Randomized trial PubMed · Publisher

  Abstract

  Background: The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group.

  Methods: After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided.

  Results: With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males.

  Conclusions: The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

• Variations in lung cancer risk among smokers. P.B. Bach, M.W. Kattan, M.D. Thornquist, et al. 2003;95(6):470-8. PubMed · Publisher

  Abstract

  Background: Although there is no proven benefit associated with screening for lung cancer, screening programs are attracting many individuals who perceive themselves to be at high risk due to smoking. We sought to determine whether the risk of lung cancer varies predictably among smokers.

  Methods: We used data on 18 172 subjects enrolled in the Carotene and Retinol Efficacy Trial (CARET)-a large, randomized trial of lung cancer prevention-to derive a lung cancer risk prediction model. Model inputs included the subject's age, sex, asbestos exposure history, and smoking history. We assessed the model's calibration by comparing predicted and observed rates of lung cancer across risk deciles and validated it by assessing the extent to which a model estimated on data from five CARET study sites could predict events in the sixth study site. We then applied the model to evaluate the risk of lung cancer among smokers enrolled in a study of lung cancer screening with computed tomography (CT).

  Results: The model was internally valid and well calibrated. Ten-year lung cancer risk varied greatly among participants in the CT study, from 15% for a 68-year-old man who has smoked two packs per day for 50 years and continues to smoke, to 0.8% for a 51-year-old woman who smoked one pack per day for 28 years before quitting 9 years earlier. Even among the subset of CT study participants who would be eligible for a clinical trial of cancer prevention, risk varied greatly.

  Conclusions: The risk of lung cancer varies widely among smokers. Accurate risk prediction may help individuals who are contemplating voluntary screening to balance the potential benefits and risks. Risk prediction may also be useful for researchers designing clinical trials of lung cancer prevention.

• Chemoprevention or antichemoprevention? A salutary warning From the beta-carotene experience. M. Paolini, S.Z. Abdel-Rahman, G. Cantelli-Forti, et al. 2001;93(14):1110-1. Comment · Letter PubMed · Publisher

  Summary

  In this letter, Paolini and colleagues noted that the ATBC and CARET chemoprevention trials had shown that beta-carotene, alone or combined with vitamins A or E, could increase lung cancer incidence and mortality in heavy smokers and asbestos workers. They summarised their own earlier laboratory findings. In an animal model, beta-carotene supplementation greatly increased lung production of cytochrome P450 (CYP) carcinogen-bioactivating enzymes, and this was associated with oxidative stress. In the BALB/c 3T3 bioassay, which they reported correlates 70%–85% with in vivo carcinogenesis, beta-carotene markedly enhanced the conversion of 3-methylcholanthrene and benzo[a]pyrene to ultimate carcinogens. Blocking the CYP increase or the overproduction of reactive oxygen species removed these effects. The authors argued that genetic polymorphisms in bioactivating, detoxifying or DNA repair enzymes could confound trial results. They said mechanistic and toxicologic studies, and the genetic make-up of trial populations, should be considered before human trials. They also supported continued advice on high fruit and vegetable intake and on smoking cessation. In a published response, Omenn described oxidative metabolites of beta-carotene and a ferret study. In that study, a dose equivalent to 30 mg per day in humans caused proliferative changes and squamous metaplasia in the lung, while one fifth of that dose did not. He disputed the letter's pessimistic conclusion about chemoprevention.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

1990s

• Possible role of ovarian epithelial inflammation in ovarian cancer. R.B. Ness, C. Cottreau. 1999;91(17):1459-67. Review PubMed · Publisher

  Abstract

  Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

• Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke. X.D. Wang, C. Liu, R.T. Bronson, et al. 1999;91(1):60-6. PubMed · Publisher

  Abstract

  Background: Epidemiologic studies have demonstrated that individuals who eat more fruits and vegetables and/or have high levels of serum beta-carotene have a lower risk of cancer, especially lung cancer. However, recent human intervention studies using beta-carotene supplements have shown an increase in the risk of lung cancer among smokers and asbestos workers. In this study, we used an animal model system to evaluate the hazard associated with a combination of high-dose beta-carotene supplementation and tobacco smoking.

  Methods: Ferrets were given a beta-carotene supplement, exposed to cigarette smoke, or both for 6 months. Cell proliferation and squamous metaplasia in lung tissue were assessed by examination of proliferating-cell nuclear antigen expression and histopathologic examination, respectively. beta-Carotene and retinoid concentrations in lung tissue and plasma samples were analyzed by high-performance liquid chromatography. Expression of genes for retinoic acid receptors (RARs) and activator protein-1 (encoded by the c-Jun and c-Fos genes) in lung tissue specimens was examined by western blotting.

  Results: A strong proliferative response in lung tissue and squamous metaplasia was observed in all beta-carotene-supplemented animals, and this response was enhanced by exposure to tobacco smoke. When compared with control groups, all three treatment groups had statistically significantly lower concentrations of retinoic acid in lung tissue, and they exhibited 18%-73% reductions in RARbeta gene expression; however, RARalpha and RARgamma gene expression was not reduced. Ferrets given a beta-carotene supplement and exposed to tobacco smoke had threefold to fourfold elevated expression of the c-Jun and c-Fos genes.

  Conclusions: Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.

• Beta carotene fails to prevent cancer in two major studies; CARET intervention stopped. K. Smigel. 1996;88(3-4):145. News PubMed · Publisher

  Summary

  This news report, published in February 1996, described two large trials of beta carotene supplements whose results were announced at a press conference before journal publication. In the Physicians' Health Study, led by Charles Hennekens, 22,071 male doctors took 50 mg of beta carotene every other day for more than 12 years. The supplement did not reduce the number of cancers, heart attacks, or deaths of any type. The Beta Carotene and Retinol Efficacy Trial (CARET) enrolled 14,254 current and former smokers with a long smoking history and 4,060 asbestos-exposed individuals, most of whom also smoked. It was stopped 21 months early because participants taking 30 mg of beta carotene plus 25,000 international units of vitamin A had 28% more lung cancers than those taking placebo. After an average of 4 years they also had 17% higher total mortality and 26% higher cardiovascular mortality. Participants were to be followed for at least 5 more years. Investigator Gilbert Omenn said former smokers seemed to respond more favorably, but the data were too limited to draw conclusions. The report noted that a 1994 trial of 29,133 male smokers had found an 18% increase in lung cancers and an 8% increase in deaths with 20 mg of beta carotene daily. National Cancer Institute Director Richard Klausner said the studies showed that a healthful diet and lifestyle cannot be replaced with simple pills.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders. A. Hirvonen, S.T. Saarikoski, K. Linnainmaa, et al. 1996;88(24):1853-6. PubMed · Publisher

  Abstract

  Background: Humans vary in their ability to metabolize endogenous and exogenous compounds. Glutathione S-transferases (GSTs) and N-acetyltransferases (NATs) are enzymes involved in the detoxification of hazardous agents. The GSTM1 and GSTT1 genes exhibit null (i.e., deletion) polymorphisms; in specific individuals, homozygous deletion (i.e., both copies lost) of these genes can be detected. Polymorphism of the NAT2 gene results in slow and fast acetylators of potentially toxic substances. The GSTM1-null and the NAT2 slow-acetylator genotypes have been associated with increased risks for the development of environmentally induced cancers.

  Purpose: We assessed whether homozygous GSTM1-null or GSTT1-null genotypes or the NAT2 slow-acetylator genotype were associated with increased risks for the development of malignant and nonmalignant asbestos-related pulmonary disorders in a cohort of Finnish construction workers.

  Methods: The study population consisted of 145 asbestos insulators who were classified as having been exposed to high levels of asbestos; 69 of these individuals had no pulmonary disorders (control subjects), and 76 had either malignant mesothelioma (n = 24) or nonmalignant pulmonary disorders, such as asbestosis and/or pleural plaques (n = 52). Lymphocyte DNA and the polymerase chain reaction were used to determine the GSTM1, GSTT1, and NAT2 genotypes of the study subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) estimating the relative risks of disease associated with specific genotypes were calculated from 2 x 2 tables by use of Fisher's exact method.

  Results: Risks for the development of asbestos-related pulmonary disorders were not affected significantly by homozygous deletion of the GSTM1 or GSTT1 genes. However, the risk of developing both malignant and nonmalignant pulmonary disorders for individuals with a NAT2 slow-acetylator genotype was more than twice that observed for those with a NAT2 fast-acetylator genotype (OR = 2.3; 95% CI = 1.1-4.7); the risk of developing malignant mesothelioma for NAT2 slow acetylators was increased almost fourfold (OR = 3.8; 95% CI = 1.2-14.3). Individuals who lacked the GSTM1 gene and possessed a NAT2 slow-acetylator genotype had a risk of developing malignant and nonmalignant pulmonary disorders that was approximately fivefold greater than that observed for those who had the GSTM1 gene and a NAT2 fast-acetylator genotype (OR = 5.1; 95% CI = 1.6-17.6); these individuals had a fourfold increased risk of developing nonmalignant pulmonary disorders (OR = 4.1; 95% CI = 1.1-17.2) and an eightfold increased risk of developing malignant mesothelioma (OR = 7.8; 95% CI = 1.4-78.7) when compared with the same reference group.

  Conclusions: Individuals with homozygous deletion of the GSTM1 gene and a NAT2 slow-acetylator genotype who are exposed to high levels of asbestos appear to have enhanced susceptibility to asbestos-related pulmonary disorders.

• Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. G.S. Omenn, G.E. Goodman, M.D. Thornquist, et al. 1996;88(21):1550-9. Randomized trial PubMed · Publisher

  Abstract

  Background: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality.

  Purpose: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention.

  Methods: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests.

  Results: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations.

  Conclusions: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

• Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California. S.J. London, A.K. Daly, J. Cooper, et al. 1995;87(16):1246-53. PubMed · Publisher

  Abstract

  Background: Glutathione S-transferase M1 (GSTM1) is active in the detoxication of a number of carcinogens, including polyaromatic hydrocarbons, such as those present in cigarette smoke. In about 30%-55% of individuals, depending on the ethnic group, there is a virtual absence of GSTM1 enzyme activity due to deletion of both copies of the GSTM1 gene (GSTM1 null genotype). This genetic polymorphism of the GSTM1 gene locus has been proposed as a risk factor for lung cancer. However, results across studies are inconsistent.

  Purpose: We conducted a case-control study of patients with incident lung cancer and population control subjects to examine the association between homozygous deletion of the GSTM1 gene and lung cancer risk among African-Americans and Caucasians.

  Methods: At 35 hospitals in Los Angeles County, California, we identified patients with a first diagnosis of lung cancer between September 1, 1990, and January 6, 1994. Of the 859 potentially eligible case patients, 207 had died by the time their physicians had received our request for permission to contact them. We enrolled 356 eligible case patients (167 African-Americans and 189 Caucasians) and 731 eligible control subjects (258 African-Americans and 473 Caucasians, all residents of Los Angeles County). Samples of white blood cell DNA sufficient for determination of the GSTM1 genotype by a polymerase chain reaction-based assay were obtained from 342 case patients and 716 control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene, in total and after stratification by a number of relevant characteristics, were estimated by logistic regression analysis.

  Results: For patients with all lung cancers combined, the GSTM1 null genotype was associated with an OR of 1.29 (95% CI = 0.94-1.77). The OR was similar among African-Americans (OR = 1.20; 95% CI = 0.72-2.00) and Caucasians (OR = 1.37; 95% CI = 0.91-2.06). The association was strongest for squamous cell carcinoma (OR = 1.57; 95% CI = 0.93-2.63). We observed an OR of 1.77 (95% CI = 1.11-2.82) for the GSTM1 null genotype in relation to lung cancer risk among smokers of less than 40 pack-years, but no association among heavier smokers (OR = 0.90; 95% CI = 0.56-1.44).

  Conclusions: Our data do not support a substantial association between homozygous deletion of the GSTM1 gene and the risk of lung cancer overall in this population. However, our data do suggest an elevated risk for lighter smokers with this genotype.

  Implications: Because the power of our analyses within strata of lifetime smoking history was limited, larger studies will be needed to confirm these findings.

• Asbestos exposure. D.L. Davis. 1992;84(7):537-8. Comment · Letter PubMed · Publisher

• Asbestos-related cancer. M.A. Schneiderman. 1992;84(14):1125. Letter PubMed · Publisher

• Association of asbestos exposure with colorectal adenomatous polyps and cancer. A.I. Neugut, T.I. Murray, G.C. Garbowski, et al. 1991;83(24):1827-8. PubMed · Publisher

  Summary

  This brief communication examined whether asbestos exposure was associated with colorectal adenomatous polyps, which are generally accepted as precursors of most colorectal cancers, as well as with colorectal cancer. The authors carried out a case-control study of patients aged 35-84 years who underwent colonoscopy in three practices at two major medical centers in New York City between April 1986 and March 1988. Of 2879 patients, 2334 were eligible and 1892 were interviewed by telephone or mail. Because almost no women reported asbestos exposure, the analysis was limited to men: 51 colorectal cancer cases, 153 adenomatous polyp cases, and 195 controls free of colorectal neoplasia. Men were asked whether they had ever been exposed to asbestos. Two occupational medicine physicians, blinded to case or control status, then reviewed the answers to identify significant exposure. Odds ratios were adjusted for age using logistic regression. Of the 56 men who reported any exposure, 12 were judged to have potentially significant exposure. Any reported exposure was not associated with significantly raised risk. For significant exposure, the odds ratio was 4.3 (95% CI 0.8-23.5) for cancer and 3.6 (95% CI 0.8-15.7) for adenomatous polyps. The authors described these elevations as borderline and their findings as preliminary, citing small numbers and wide confidence intervals. They suggested an endoscopic screening study of an asbestos-exposed occupational cohort.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Lung cancer and the debrisoquine metabolic phenotype. N.E. Caporaso, M.A. Tucker, R.N. Hoover, et al. 1990;82(15):1264-72. PubMed · Publisher

  Abstract

  In a case-control study, we tested the hypothesis that the genetically determined ability to metabolize debrisoquine is related to risk of lung cancer. Overall, individuals who were extensive metabolizers of debrisoquine were at significantly greater risk of lung cancer than those who were poor or intermediate metabolizers (odds ratio = 6.1; 95% confidence interval = 2.2-17.1). In this study, case patients had lung cancer, and control subjects had either chronic obstructive pulmonary disease or cancers other than lung cancer. Results were adjusted for age, race, asbestos exposure, and smoking. Both black and white individuals who were extensive metabolizers of debrisoquine were at significantly increased risk after similar adjustment (for blacks, odds ratio = 4.5, 95% confidence interval = 1.1-18.1; for whites, odds ratio = 10.2, 95% confidence interval = 2.0-51.4). Significantly increased risk of lung cancer was also present for individuals who were extensive metabolizers when subjects with chronic obstructive pulmonary disease or other cancers were considered separately. These data confirm that the ability to metabolize debrisoquine is a major determinant of susceptibility to lung cancer. Evaluation of the marker in other case-control settings, further exploration of racial differences, and the prospective evaluation of this marker in subgroups at high risk of lung cancer are areas worthy of further study.

1980s

• Tumorigenicity of human mesothelial cell line transfected with EJ-ras oncogene. R.R. Reddel, L. Malan-Shibley, B.I. Gerwin, et al. 1989;81(12):945-8. PubMed · Publisher

  Abstract

  We performed this study to determine whether human mesothelial cells are capable of undergoing neoplastic change in vitro and to observe their interaction with the activated c-Ha-ras (HRAS1) oncogene EJ-ras, which has a role in the development of many malignant human tumors. Mesothelial cells are presumed to be the progenitor cells of malignant mesothelioma, a cancer strongly correlated with asbestos exposure. Previously, we established a non-tumorigenic cell line, MeT-5A, from normal human mesothelial cells after transfection with a plasmid containing the simian virus 40 (SV40) early-region genes. In the present study, we performed transfection of a plasmid containing the EJ-ras gene and the neomycin-resistance gene into these cells and selected a population resistant to G418, a neomycin analogue. Cells from this cell line formed rapidly growing sc tumors in NIH Swiss athymic nude mice, but untransfected with the vector DNA and selected for G418 resistance formed no tumors. The tumors formed by EJ-ras-transfected cells were established in vitro, and cells from these tumor cell lines exhibited a characteristic altered morphology. The cells had the same isoenzyme phenotype as the parent cells, and they expressed the mutant EJ-ras p21 protein. This first demonstration of malignant transformation of human mesothelial cells in vitro may permit molecular analysis of mesothelial carcinogenesis.

• Direct enhancement by cigarette smoke of asbestos fiber penetration and asbestos-induced epithelial proliferation in rat tracheal explants. J. Hobson, B. Gilks, J. Wright, et al. 1988;80(7):518-21. PubMed · Publisher

  Abstract

  Tracheal explants from Sprague-Dawley rats were briefly exposed to cigarette smoke or air (control) and then to amosite asbestos. Asbestos fibers in or under the tracheal epithelium were counted and extent of hyperplastic lesions was ascertained at 24 hours, 72 hours, and 1 week after exposure. Smoke-exposed cultures showed significantly greater numbers of fibers in the epithelium and greater proliferative activity compared to findings in cultures not exposed to smoke. These observations indicate that very short exposure to cigarette smoke can directly affect the response of the epithelium to asbestos fibers and that smoke exposure need not be concurrent with asbestos exposure for such event to occur. These reactions may play a role in the greater incidences of lung cancer and asbestosis seen in asbestos-exposed workers who smoke.

• Use of job-exposure matrix in an occupational analysis of lung and bladder cancers on the basis of death certificates. D. Coggon, B. Pannett, E.D. Acheson. 1984;72(1):61-5. PubMed · Publisher

  Abstract

  A job-exposure matrix has been applied in a case-control study of lung and bladder cancer on the basis of occupational information abstracted from British death certificates. The expected association between lung cancer and jobs entailing exposure to asbestos was clearly demonstrated (relative risk, 1.5; 95% confidence interval, 1.2-1.9). The effects of three other known industrial carcinogens were not apparent, and reasons for this were discussed. Also included in the matrix were five substances whose carcinogenicity in humans has not been established. Formaldehyde, diesel fumes, and cutting oils were all associated with carcinoma of the bronchus, but the absence of a risk in "high-exposure" occupations was against a causal relationship. Bladder cancer was more common in jobs involving high exposure to printing inks (relative risk, 5.0; 95% confidence interval, 1.0-25.8) and cutting oils (relative risk, 1.5; 95% confidence interval, 0.8-2.8). Use of the job-exposure matrix added considerably to the conventional analysis of cancer risk in individual occupational categories.

1970s

• Cancer in asbestos-mining and other areas of Quebec. S. Graham, M. Blanchet, T. Rohrer. 1977;59(4):1139-45. PubMed · Publisher

  Abstract

  Employing incidence data from the Quebec Tumor Registry, we examined the relative risks of cancer of all sites for the years 1969-73 in the asbestos-mining, rural, and metropolitan counties of Quebec Province, Canada. Generally, rates for males exceeded those for females, and the relative risks in the asbestos-mining counties for 7-10 different sites of cancer, all of low incidence, were from 1.50 to 8.08 times those of other rural counties of the Province for both sexes. Metropolitan counties exhibited equally high risk for many of these sites. We discovered higher risks among males in asbestos-mining counties for cancer of the pleura, peritoneum, lip, tongue, salivary gland, mouth, and small intestine and higher risks among females for cancer of the pleura, lip, kidney, salivary gland, and for melanoma. Because of the likelihood of a long latent period for asbestos-related cancers, the risks we observed were possibly the product of since-altered occupational and environmental conditions existing 20-30 years ago in the asbestos-mining areas. The similarities in risks for most cancers in asbestos-mining and urban areas were noteworthy.

• Carcinogenicity of fibrous glass: pleural response in the rat in relation to fiber dimension. M.F. Stanton, M. Laynard, A. Tegeris, et al. 1977;58(3):587-603. PubMed · Publisher

  Abstract

  Seventeen fibrous glasses of diverse type or dimensional distribution induced different incidences of malignant mesenchymal neoplasms when implanted in the pleurae of female Osborne-Mendel rats for periods of more than 1 year. Neoplastic response correlated well with the dimensional distribution of fibers. Fibers less than or equal to 1.5 mu in diameter and greater than 8 mu in length yielded the highest probability of pleural sarcomas, and probability trends suggested that pleural sarcoma incidence increased with increasing lengths of fibers with diameters of less than 1.5 mu, Morphologic observations indicated that fibers less than or equal to 8 mu in length were inactivated by phagocytosis. In fibers greater than 8 mu in length, the correlation of carcinogenicity witth increasing length was difficult to explain. Since neoplastic response to a variety of types of durable fibers, particularly asbestos fibers, was similar, our experiments reinforce the idea that the carcinogenicity of fibers depends on dimension and durability rather than physicochemical properties and emphasize that all respirable fibers be viewed with caution.

• Respiratory carcinogenesis: an epidemiologic appraisal. J.F. Fraumeni. 1975;55(5):1039-46. Review PubMed · Publisher

  Summary

  In this solicited guest editorial, the author reviewed the epidemiologic evidence for causes of respiratory cancer other than cigarette smoking and noted opportunities for further research. He summarized studies of occupational agents: radioisotopes (including radon daughters in uranium and other miners), mustard gas, asbestos, polycyclic aromatic hydrocarbons, halo ethers, nickel, chromium, inorganic arsenic, iron ore, wood dust, the shoe industry and isopropyl oil. For asbestos, he reported several findings. The risks of asbestosis, lung cancer and mesothelioma were substantially raised among asbestos workers. Lung cancer incidence varied with the extent of exposure to all fiber types. Mesothelioma risk was thought to be greater after crocidolite exposure. Cigarette smoking greatly enhanced lung cancer risk after asbestos exposure. He also discussed community pollution, including mesotheliomas among family members of asbestos workers and neighborhood residents. Other factors covered were alcohol, nutrition, drugs, and genetic and immunologic susceptibility. He described county-level mapping of U.S. lung cancer mortality among white males in 1950-69, which showed clustering in the Northeast and along the southeast Atlantic and Gulf coasts. The author concluded that well-designed occupational studies would continue to be the most rewarding means of identifying risk factors in respiratory carcinogenesis. He called for record-linkage systems matching employment records with cancer registration and death certificates.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Editorial: Fiber carcinogenesis: is asbestos the only hazard?. M.F. Stanton. 1974;52(3):633-4. PubMed · Publisher

  Summary

  In this editorial, the author, from the Laboratory of Pathology at the National Cancer Institute, argued that asbestos causes cancer because of the physical structure of its fibers rather than its chemical composition. He asked whether other durable fibers pose a similar hazard. He drew on experiments from his own and other laboratories in which various fibers were implanted in the pleura of rats and produced sarcomas essentially the same as asbestos-induced mesotheliomas in humans. He reported several findings from these studies. Hydrocarbons and metal-mineral complexes associated with asbestos did not account for its carcinogenicity. Asbestos types differing widely in physicochemical structure showed little difference in carcinogenicity when milled to similar sizes. Fine, long fibers of glass and aluminum oxide were similarly carcinogenic, while nonfibrous particles and exceptionally short fibers were far less so. As a conservative estimate, durable fibers under 3 µm in diameter and over 20 µm in length were far more carcinogenic in the rat pleura than fibers of other dimensions. Preliminary data suggested that exceptionally long glass fibers under 0.5 µm in diameter were highly carcinogenic. He noted that durable fibers are widespread in products, air and water, and are found in nearly all human lungs. He proposed measuring the number and size distribution of all fibers in human tissues. He concluded that durable fibers may cause cancer simply because they are fibers, irrespective of their physicochemical nature, and urged vigilance.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Experimental studies on asbestos carcinogenicity. L.M. Shabad, L.N. Pylev, L.V. Krivosheeva, et al. 1974;52(4):1175-87. PubMed · Publisher

  Abstract

  The carcinogenic activity of different types of asbestos of the USSR was investigated. All samples of chrysotile had traces of benzo[a]pyrene (BP). Chrysotile asbestos had a high adsorption activity. BP was not found in anthophyllite and magnesioarfvedsonite. Intratracheal injections and inhalations of different kinds of chrysotile induced pulmonary carcinomas, sarcomas, and precancerous lesions in rats. The number of such lesions was higher if asbestos and BP were introduced together. Intrapleural administration of chrysotile asbestos induced several types of mesothelioma and premesotheliomatous lesions in rats. A transplantable mesothelioma (MSh-71) is in its twenty-sixth generation.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Histogenesis and fine structure of peritoneal tumors produced in animals by injections of asbestos. J.M. Davis. 1974;52(6):1823-37. PubMed · Publisher

  Abstract

  Primary tumors of the peritoneal cavity were produced in rats and mice by the intraperitoneal injection of crocidolite asbestos. The earliest discernible neoplastic stage consisted of many small, pedunculated nodules scattered over the surfaces of the viscera, diaphragm, and body wall. These nodules contained a central core of reticulin or collagen surrounded by layers of pleomorphic connective-tissue cells. The surfaces of the nodules were covered by a single layer of epithelial cells similar to normal mesothelium. In later stages some nodules remained distinct and became quite large, but often the tumor spread over the peritoneal surfaces as a uniform sheet. The cells found in sheets were mostly of the same type as those in large nodules: pleomorphic connective-tissue cells in the central regions and epithelial cells on the surface. In some advanced tumors, however, the cells had a spindle-cell pattern similar to a fibroma or fibrosarcoma. In this form the neoplasms were locally invasive; however, at earlier stages no signs of invasion could be detected. Electron microscope studies showed only a slight difference in ultrastructure between the different tumor cell types, and it is suggested that the growths arose from undifferentiated mesenchymal cells in the submesothelial tissues. These cells retained their normal pleomorphic pattern or gave rise to either epithelial (mesothelial) cells on free surfaces or spindle cells in deeper layers.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Ultrastructure of human mesotheliomas. J.M. Davis. 1974;52(6):1715-25. PubMed · Publisher

  Abstract

  An electron microscope study of 5 human biopsy specimens from suspected mesotheliomas showed that the tumor cell fine structure was usually similar to that of mesotheliomas produced in laboratory animals by the intraperitoneal injection of asbestos dust. In most instances, the tumor cells had a well-developed granular endoplasmic reticulum, and the cell cytoplasm often contained bundles of microfilaments. In some, these microfilaments made up a large part of the cell volume. Glycogen was found in all the neoplasms examined, and some had large amounts. Lipid granules, seen in the cytoplasm of many tumor cells, had a characteristic crenated surface. The cell surface membranes were characteristically modified to form numerous surface processes of variable type found usually around most of the cell circumference. The processes ranged from irregularly shaped microvilli to globular projections like miniature pseudopodia, and often these 2 forms were intermingled on the same cell. One biopsy specimen that did not conform to this general pattern was proved at autopsy to be a bronchial carcinoma with secondary spread into the pleural cavity. This indicated that electron microscope examination may be extremely useful as an aid to diagnosis when only small biopsy specimens are available.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters. W. Dontenwill, H.J. Chevalier, H.P. Harke, et al. 1973;51(6):1781-832. PubMed · Publisher

• Tumors of the pleura induced with asbestos and fibrous glass. P. Gross. 1973;51(1):315-7. PubMed · Publisher

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