Bronchial epithelial Ki-67 index is related to histology, smoking, and gender, but not lung cancer or chronic obstructive pulmonary disease.

PURPOSE: To determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer. EXPERIMENTAL DESIGN: Cross-sectional study of 113 subjects undergoing white light and autofluorescence bronchoscopy: 27 never smokers; 27 current or ex-smokers with normal spirometry; 31 current or ex-smokers with COPD; and 28 current, ex-, or never smokers with lung cancer. Ki-67 expression was determined by immunohistochemistry on all evaluable biopsy sites without carcinoma. Relationships between Ki-67 index (percentage of epithelial cells expressing Ki-67), demographic variables, smoking, histology, and the presence of COPD and/or lung cancer were determined. RESULTS: Results for both maximal and mean Ki-67 index are similar, so only the former are reported. Average maximal Ki-67 index was higher in current smokers than either ex-smokers or never smokers (48.0% versus 30.6% versus 22.6%; P<0.001). Males had higher Ki-67 index than females (39.9% versus 23.6%; P<0.001). Compared with subjects without disease (Ki-67 index=30.0%), maximal Ki-67 index was not significantly elevated (P=0.44) in subjects with either lung cancer (Ki-67=39.1%) or COPD (Ki-67=38.9%). CONCLUSIONS: Smoking status, bronchial histology, and gender were significantly associated with Ki-67 index. No increase in Ki-67 index was found in the nonmalignant epithelium of patients with lung cancer or COPD. Although Ki-67 index may provide insight into the short-term effects of chemoprevention agents on cell proliferation, its lack of association with lung cancer or COPD raises question regarding its utility as a lung cancer risk biomarker.     

Smoking and lung cancer in Harbin, northeast China.

BACKGROUND: We studied the relationship between smoking and lung cancer risk in Harbin, Heilongjiang province, northeast China, an area with a very high baseline risk of lung cancer in both sexes, using data from a case-control study of lung cancer conducted between 1987 and 1990. PATIENTS AND METHODS: Cases were 218 patients with incident, histologically confirmed lung cancer and controls were 436 patients admitted to the same hospital with non-neoplastic and non-lung diseases. RESULTS: Compared with never-smokers, the multivariate odds ratio (OR) for current smokers was 3.47 [95% confidence interval (CI) 2.31--5.20], and for ex-smokers 1.53 (95% CI 0.81--2.87). Lung cancer risk increased by 20% (95% CI 14% to 28%) for an increment of 5 years in smoking duration, and by 29% (95% CI 15% to 45%) for an increment of five cigarettes per day. The OR for smokers reporting occupational exposure to selected known or likely lung carcinogens was 7.22, compared with non-smokers without occupational exposure. CONCLUSIONS: This study further confirms that cigarette smoking is a strong determinant of lung cancer also in this high-risk area of northeast China.     

Clinical study of asbestos‐related lung cancer in Japan with special reference to occupational history

A total of 152 patients with asbestos‐related lung cancer recognized by the criteria of Japanese compensation law for asbestos‐related diseases were examined and compared with 431 patients with non‐asbestos‐related lung cancer. Male comprised 96% of patients. Ages ranged from 50 to 91 years with a median of 72 years. Eighty‐nine percent were smokers or ex‐smokers. Almost all patients had occupational histories of asbestos exposure. The median duration of asbestos exposure was 31 years and the median latency period was 47 years. Thirty‐four percent of patients exhibited asbestosis and 81% exhibited pleural plaques by radiography. Regarding asbestos particles in the lung for 73 operated or autopsied patients, 62% had more than 5,000 particles per gram. On the other hand, 100% of non‐asbestos‐related lung cancer patients had <5000 particles per gram with a median of 554 particles. The number of asbestos bodies in the lung, male gender, absence of symptoms, smoking index, and early stage of cancer were significantly much more than those of non‐asbestos‐related lung cancer. In this study, a diagnosis of asbestos‐related lung cancer was made in 34% of patients by asbestosis, in 62% by presence of both pleural plaques and more than 10 years’ occupational asbestos exposure, and in 4% by more than 5000 asbestos particles per gram of lung tissue. Occupational histories, duration of asbestos exposure, and pleural plaques are common categories for the recognition of asbestos‐related lung cancer in Japan. (Cancer Sci 2010; 101: 1194–1198)     

DNA adducts in bronchial biopsies

To investigate the feasibility of measuring DNA-carcinogen adducts in the lungs of non-surgical patients, endobronchial biopsies were obtained from 78 patients undergoing routine diagnostic bronchoscopy. Lung cancer was present in 37 (47%) of the patients. DNA was isolated from the tissues and analyzed by HPLC- or nuclease-PI-enriched 32P-postlabelling, using procedures selective for aromatic adducts. Chromatograms from all 28 current smokers showed a distinctive diagonal adduct zone which was present in only 24 of 40 ex-smokers and 4 of 10 lifetime non-smokers. Adduct levels and chromatographic patterns were similar in bronchial tissue from different lobes of the lung, in bronchial and alveolar tissue, and in tumor and non-tumor bronchial tissue taken from the same subject. Bronchial DNA adduct levels were strongly associated with cigarette smoking status and dropped rapidly after smoking ceased. Higher levels of DNA adducts seen in the lung-cancer patients were mainly due to cigarette smoking. Frequent alcohol intake was the only dietary factor associated with higher levels of bronchial DNA adducts. We conclude that the level of bronchial DNA adducts is strongly associated with cigarette-smoking history and with alcohol intake, but is not associated with lung cancer independently from its relation to smoking. The results indicate the feasibility of using 32P-postlabelling to detect and quantitate genetic damage in bronchial biopsy specimens.     

Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI and GSTM1 genotypes in lung patients

Relationships between smoking status and levels of bulky DNA adducts were investigated in bronchial tissue of lung patients in relation to their GSTM1 and CYP1A1 MspI genotypes. A total of 150 Hungarian patients undergoing pulmonary surgery were included in the study, 124 with lung malignancies and 26 with non-malignant lung conditions. There were significant relationships between smoking status and bulky DNA adduct levels, as determined by 32P-post-labelling analysis, in macroscopically normal bronchial tissues. There was a highly significant difference in the adduct levels of a combined group consisting of current smokers and short-term ex-smokers (< or = 1 year abstinence) compared with life-time non-smokers and long-term ex- smokers (> 1 year abstinence) (P = 0.0001). The apparent half-life was estimated to be 1.7 years for bulky DNA adducts in the bronchial tissue from ex-smokers. There were no statistically significant correlations between (i) daily cigarette dose and DNA adduct levels in current smokers, (ii) DNA adduct level and histological type of lung cancer, or (iii) GSTM1 and CYP1A1 MspI genotypes and DNA adduct levels after adjustment for either smoking status or malignancy. By multiple logistic regression analysis, smoking and GSTM1 null genotype were found to be risk factors for squamous cell carcinoma. However, bulky DNA adduct levels in bronchial tissue did not appear to be a statistically-significant risk factor for the major histological types of lung cancer.      

Smoking cessation before diagnosis and survival in early stage non-small cell lung cancer patients

Smoking cessation decreases the risk of lung cancer. However, little is known about how smoking cessation affects lung cancer survival. We examined the association between smoking cessation and overall survival (OS) and recurrence-free survival (RFS) in 543 early stage non-small cell lung cancer (NSCLC) patients. The data were analyzed using log-rank test and Cox proportional hazard models, adjusting for age, gender, stage, and smoking intensity. The median follow-up time was 57 months (range 0.2-140 months). There were 191 recurrences and 285 deaths. The 5-year OS rates were 50% (95% confidence interval (CI), 43-58%) for current smokers, 54% (44-65%) for ex-smokers who quit 1-8 years, 59% (49-70%) for ex-smokers who quit 9-17 years, 58% (47-69%) for ex-smokers who quit > or =18 years prior to diagnosis, and 76% (63-90%) for never smokers (P=0.09, log-rank test). The adjusted hazard ratios for ex-smokers who quit 1-8, 9-17, > or =18 years, and never smokers were 0.82 (95% CI, 0.59-1.13), 0.69 (0.49-0.97), 0.66 (0.45-0.95), and 0.54 (0.29-0.996), respectively, when compared with current smokers (P(trend)=0.004). Similar associations were found among ever smokers-only, when smoking cessation time was treated as a continuous variable, and for RFS. The significantly beneficial effects of smoking cessation on OS and RFS were observed among women only, while not among men (P=0.01 for interactions between gender and smoking cessation). In conclusion, smoking cessation is associated with improved survival in early stage NSCLC patients. The longer the time since cessation of smoking, the better the survival outcome.     

Occupational exposures contribute to educational inequalities in lung cancer incidence among men: Evidence from the EPIC prospective cohort study

The aim of this study is to investigate to what extent occupational exposures may explain socioeconomic inequalities in lung cancer incidence after adjusting for smoking and dietary factors. Analyses were based on a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC study), a prospective cohort. The analyses included 703 incident lung cancer cases among men in Denmark, the United Kingdom, Germany, Italy, Spain and Greece. The socioeconomic position was measured using the highest level of education. The estimates of relative indices of inequality (RII) were computed with Cox regression models. We first adjusted for smoking (with detailed information on duration and quantity) and dietary factors (fruits and vegetables consumption) and then for occupational exposures. The exposure to three carcinogens [asbestos, heavy metals and polycyclic aromatic hydrocarbons (PAH)] was analyzed. The occupational exposures explained 14% of the socioeconomic inequalities remaining after adjustment for smoking and fruits and vegetables consumption. The inequalities remained nevertheless statistically significant. The RII decreased from 1.87 (95% CI: 1.36–2.56) to 1.75 (1.27–2.41). The decrease was more pronounced when adjusting for asbestos than for heavy metals or PAH. Analyses by birth cohort suggested an effect of occupational exposures among older men, while due to small number of endpoints, no conclusion could be drawn about the role of occupational exposures in educational inequalities among younger men. Our study revealed that the impact of occupational exposures on socioeconomic inequalities in cancer incidence, rarely studied until now, exists while of modest magnitude.     

Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype

The risk of lung cancer in smokers was examined based on the debrisoquine metabolic phenotype and on exposure to occupational lung carcinogens, specifically asbestos and polycyclic aromatic hydrocarbons. Extensive metabolizers of debrisoquine are at a 4-fold increased risk for lung cancer compared to poor metabolizers, after adjustment for age, sex, and smoking (pack-years), when only occupationally unexposed subjects are considered. Increased risk related to the debrisoquine metabolic phenotype was greatest for squamous and small cell histologies, and least for the adenocarcinoma subtype. Men with a history of exposure to occupational carcinogens had significantly increased risk of lung cancer (relative risk = 2.8), after adjustment for age and smoking. Considering the combined effect of the high risk extensive metabolizers debrisoquine metabolic phenotype and likely occupational exposure to asbestos, the relative excess risk for lung cancer was 18-fold. This finding is consistent with a synergism in risk between the ability to extensively metabolize debrisoquine and occupational exposure to lung carcinogens in male smokers. Debrisoquine phenotyping has potential for identifying carcinogen-exposed workers at high risk of lung cancer.     

Risk factors for lung cancer in Iowa women: implications for prevention

BACKGROUND: Multiple risk factors possibly associated with lung cancer were examined as part of a large-scale residential radon case-control study conducted in Iowa between 1994 and 1997. We were particularly interested in stratifying risk factors by smoking status. Relatively little risk factor information is available for Midwestern rural women. METHODS: Four hundred thirteen female lung cancer cases and 614 controls aged 40-84, who were residents of their current home for at least 20 years, were included. Risk factors examined included cigarette smoking, passive smoking, occupation, chemical exposure, previous lung disease, family history of cancer, and urban residence. Multiple logistic regression analysis was conducted after adjusting for age, education, and cumulative radon exposure. RESULTS: As expected, active cigarette smoking was the major risk factor for lung cancer. While cessation of smoking was significantly associated with a reduced risk for lung cancer, the risk remained significantly elevated for 25 years. Among all cases, asbestos exposure was a significant risk. Among ex-smokers, pack-year history predominated as the major risk. Among never smokers, a family history of kidney or bladder cancer were significant risk factors (OR=7.34, 95% CI=1.91-28.18; and OR=5.02, 95% CI=1.64-15.39, respectively), as was a history of previous lung disease (OR=2.28, 95% CI=1.24-4.18) and asbestos exposure. No statistically significant increase in lung cancer risk was found for occupation or urban residence. CONCLUSIONS: Smoking prevention activities are urgently needed in rural areas of the United States. Relatives of individuals with smoking-related cancers are potentially at increased risk. Genetic risk factors should be more fully investigated in never smokers.     

Quantitation of asbestos and asbestos-like fibers in human lung tissue by hot and wet ashing, and the significance of their presence for survival of lung carcinoma and mesothelioma patients.

Technical standardization on randomly chosen samples of tissue specimen is essential for the validity of interpretations derived from measurements on the presence of asbestos fibers in lung in combination with further features of the patients. Fixed non-tumorous lung tissue (2-3 g) of 150 patients after surgery for various lung diseases were either digested in 45 ml of 13% solution with sodium hypochlorite (NaClO; wet ashing) or heated in an oven at 600 degrees C for 15 min (hot ashing). After tissue disintegration asbestos and asbestos-like fibers were counted by visual inspection, and the fiber concentration in the lung parenchyma was computed. In addition, the patients' survival, and the occupational and social history were analyzed. As a result, the mean concentrations of fibers were found to be 55 f/g (fibers/gram, hot ashing) and 46 f/g (wet ashing). The difference is statistically not significant. Mesotheliomas contributed 49% (73 patients), non-small cell lung carcinomas 32% (59 patients) to the entire cohort. Eighteen patients had a non-malignant lung disease. Analysis of living habits revealed that 73 (49%) patients were heavy smokers, and 99 (66%) patients had a history of occupational asbestos exposure which lasted for 18 years on average. A statistically significant difference of the asbestos fiber concentration between the group with professional exposure and that without detectable asbestos exposure could be obtained in mesothelioma patients and non-malignant lung diseases only, and a tendency for elevated fiber presence was seen in non-small cell lung carcinoma patients. In tissue specimen of patients with non-malignant lung diseases the highest fiber concentration was measured (median 104 f/g) followed by mesothelioma patients (77 f/g), and lung carcinoma patients (62 f/g wet tissue). The difference in the fiber concentration between smokers and ex-smokers versus non-smokers was particularly high in patients with non-malignant lung diseases (103 f/g in smokers versus 33 f/g in non-smokers), still statistically significant in mesothelioma patients (100 f/g smokers versus 61 f/g non smokers), and negligible in lung carcinoma patients (58 f/g smokers versus 62 f/g non-smokers). Only 5/70 mesothelioma patients were not exposed to asbestos at work, and nearly half of the patients (36) were non-smokers. The median survival of mesothelioma patients was significantly shortened for patients with a high intrapulmonal fiber concentration greater than 70 f/g (35 weeks versus 60 weeks). This correlation was also true for lung carcinoma patients (110 weeks versus 230 weeks).     

K-ras mutations in human adenocarcinoma of the lung: Association with smoking and occupational exposure to asbestos

We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed-in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation-a clear association of K-ras mutations with heavy life-time smoking (≥50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2 - 19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6 - 8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.     

Asbestos exposure and histologic cell types of lung cancer in surgical and autopsy series

A case-control study was carried out on 41 surgical and 106 autopsy histological tissue samples of lung cancer in men, in order to investigate the relationships between asbestos exposure and cell type of pulmonary carcinoma. Both occupational history (obtained by interviews of surgical patients or of the next-of-kin for deceased subjects) and lung asbestos body content (determined by optical count after hypochlorite digestion and membrane filtration of lung tissues) were considered as asbestos exposure indicators. No significant relationships were found in the surgical series after adjustment for smoking. The autopsy series showed a trend towards an association between lung adenocarcinoma and asbestos exposure indicators and a markedly higher agreement between the 2 kinds of indicators than that observed in the surgical series.     

p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer.

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.     

Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer

Within the framework of the Liverpool Lung Project (LLP), population-based case-control and prospective cohort studies are in progress to identify molecular and epidemiological risk factors and define populations and individuals most at risk of developing lung cancer. This report describes a strategy for selection of a high-risk population and further provides support for the inclusion of occupational and genetic risk factors in future models. Data from the case-control study (256 incident cases and 314 population controls) were analysed to define a high-risk population. Detailed lifestyle and occupational information were collected during structured interviews. Models were constructed using conditional logistic regression and included terms for age, tobacco consumption and previous respiratory disease. Smoking duration was chosen as the most important predictor of lung cancer risk [>50 years (OR 15.65, 95% CI 6.10-40.15)]. However, such a model would preclude younger individuals. Several combinations of previous respiratory disease were also considered, of which a history of bronchitis, emphysema or pneumonia (BEP) was the most significant (OR 1.86, 95% CI 1.28-2.69). A high-risk subset (based on combinations of smoking duration and BEP) was identified, which have a 4.5-fold greater risk of developing lung cancer (OR 4.5, 95% CI 2.33-8.68). Future refinement of the risk model to include individuals occupationally exposed to asbestos and with the p21 genotypes is discussed. There is real potential for environmental and genetic factors to improve on risk prediction and targeting of susceptible individuals beyond the traditional models based only on smoking and age. The development of a molecular-epidemiological model will inform the development of effective surveillance, early detection and chemoprevention strategies.     

Proportion of lung cancers due to occupational exposure

The proportions of male lung cancers due to occupational exposure and, respectively, to cigarette smoking in a highly industrialized area of Northern Italy were estimated in a population-based case-control study in 1976–9. Two hundred and four out of the 211 lung cancer cases and 351 controls sampled from the source population were questioned about their occupational and smoking histories. On the basis of the occupational history each subject was classified as probably exposed (+), possibly exposed (?), or unexposed (?) to one or more of the chemicals known to be carcinogenic for the human lung, namely asbestos, polycyclic aromatic hydrocarbons, arsenic, nickel and chromium compounds, BCME, CMME and vinyl chloride. Upon stratification by cigarette smoking, contrasting the occupationally exposed subjects, whether certainly or uncertainly defined, with the unexposed ones, the RR for lung cancer was 2.1 and the occupational etiologic fraction was 0.33 (95% confidence interval 0.19–0.47). The tobacco etiologic fraction was 0.81, while the two exposures together accounted for 89% of the total burden of incident cases. If 33% of all male lung cancers were of occupational aetiology, then this alone would represent 5% of all cancer deaths.     

Surrogate end-point biomarker analysis in a retinol chemoprevention trial in current and former smokers with bronchial dysplasia

Epidemiological studies suggested that vitamin A may be protective against lung cancer, however, recent chemoprevention trials with beta-carotene, a precursor of vitamin A, demonstrated enhancement of lung carcinogenesis among smokers. Whether vitamin A is beneficial or harmful in chemoprevention of lung cancer in smokers has not been resolved. This study was designed to determine the effect of retinol alone in current and former smokers using bronchial dysplasia, nuclear morphometry and retinoic acid receptor-beta (RAR-beta) mRNA expression as surrogate end-point biomarkers (SEBs). Eighty-one current or former smokers with a smoking history of >/=30 pack-years were randomized to receive either placebo or retinol (50,000 IU per day) for six months. Fluorescence bronchoscopy was performed prior to treatment to localize areas suggestive of dysplasia. At least 4 bronchial biopsies were taken per subject including at least two biopsies from apparently normal areas. The same areas were precisely re-biopsied after 6 months. Any new areas suggestive of dysplasia were also biopsied. Changes in the SEBs were assessed before and after treatment. At baseline, the frequency of biopsies negative for RAR-beta expression was: normal (23%), hyperplasia (28%), metaplasia (41%), mild dysplasia (41%), and moderate/severe dysplasia (44%). There was no significant difference in the regression rate between the retinol and placebo groups using histopathology and nuclear morphometry as SEBs. The likelihood of regression was found to be lower in those who continued to smoke during the study (OR=1.86 for those smoking >10 cigarettes per day, p=0.084 to OR=0.95, p=0.26 for those smoking 20+ per day compared to ex-smokers). Retinol was not effective in the up-regulation of RAR-beta in lesions with bronchial dysplasia. We postulate that the lack of effect of retinol on RAR-beta expression among individuals who continued to smoke while taking retinol may be due to suppressive effect of tobacco smoke constituents on RAR-beta expression and/or altered cellular metabolism of retinol to retinoic acid and its isomers.     

Asbestos and lung cancer: An analysis of the epidemiological evidence on the asbestos—smoking interaction

Three simple models for the asbestos—smoking interaction on human lung cancer production are considered. In the first model the excess incidence of lung cancer independently due to asbestos and to smoking adds together when both agents are present (additive model). In the second the addition of each one of the two agents produces an effect (increase in lung cancer incidence) which is proportional to the effect of the other (multiplicative model). In the third, asbestos can only increase lung cancer incidence in the presence of smoking. As previously found by other investigators, the additive model appears the least plausible in the light of the data from two published epidemiological studies. A discrimination between the other two models is attempted through a detailed analysis of the five published epidemiological studies today available which provide information on occupational asbestos exposure, smoking habits and lung cancer risk. Although the data do not allow a definitive discrimination, the multiplicative model appears to be more plausible, being also consistent with a multistage carcinogenic mechanism and with evidence from animal (rat) experiments. It is relevant both for biology and for public health that in this model asbestos and smoking are regarded as independently capable of producing lung cancer in humans and that they act synergistically when exposure to both occurs.     

Evaluation of double cancers in relation to previous asbestos exposure

Ten cases of double cancers (a lung cancer and a stomach cancer) were evaluated in relation to previous asbestos exposure. Ten cases involved male more than 69 years old. Five cases had developed their two cancers simultaneously and other 5 cases had developed their lung cancer after stomach cancer surgery. The lung cancer was their main disease. Four cases had early stage stomach cancers and 5 cases with a stomach cancer had no relapse after surgery. Eight cases had occupational histories of asbestos exposure. Significantly high numbers of asbestos bodies were detected in the autopsied lung in almost all cases. According to the X-ray analysis, almost all asbestos fibers detected in the lung were chrysotile. Additionally, the Brinkman Index (B.I.) of these 10 cases ranged between 700 and 2,000. The combination of asbestos exposure and smoking is thought to be an important factor in the development of such double cancers.     

Tobacco, alcohol, asbestos, and occupational risk factors for laryngeal cancer.

Data from a hospital-based case-control study between 1985-1990 were used to examine the effects of tobacco, alcohol, asbestos, and other occupational exposures on laryngeal cancer risk in 194 white men with primary cancer of the larynx and 184 age-matched control subjects. A dose-dependent effect for current cigarette smoking was observed, with higher relative risks (RR) for supraglottic cancer (RR, 21.6 to 68) than for cancer of the glottis (RR, 5.5 to 20.7). Elevated RR for ex-smokers (RR, 4.8) and pipe and cigar smokers (RR, 4.3) did not vary by subsite. The effects of alcohol also showed dose-dependent effects, with higher RR for cancer of the supraglottis than glottis for heavy drinkers (207 ml or more/daily; RR, 9.6 versus 2.5) and binge drinkers (RR, 28.4 versus 8.3). A slightly elevated but not significant association was seen for asbestos exposure and glottic cancer (RR, 1.3). The RR did not increase linearly with the number of years employed in asbestos-related occupations. No relationship was observed between asbestos and cancer of the supraglottis. When examining the data for a synergistic effect of cigarette smoking and asbestos exposure, no excess risk was found. A significantly elevated risk was found for men exposed to diesel fumes (RR, 5.2). Elevated but not significant RR were seen for men chronically exposed to rubber (RR, 6.4) and wood dust or employed as construction laborers, auto mechanics, and other jobs. A significant inverse trend with body mass was observed for cancer of the supraglottis.     

p53 and K-ras mutations in lung cancers from former and never-smoking women

Somatic p53 mutations are common in lung cancer. Active cigarette smoking is positively correlated with the total frequency of p53 mutations and G:C to T:A transversions on the nontranscribed (DNA coding) strand. Mutational hotspots within the p53 gene, e.g., codon 157, have been identified for tobacco-related lung cancer, whereas these same mutations are found rarely in other cancers. Such data implicate specific p53 mutations as molecular markers of smoking. Because limited data exist concerning the p53 mutation frequency and spectra in ex-smokers and nonsmokers, we have analyzed p53 and K-ras mutations in 126 lung cancers from a population-based case-control study of nonsmoking (n = 117) or ex-smoking (n = 9) women from Missouri with quantitative assessments of exposure to environmental tobacco smoke. Mutations in the p53 gene were found in lung cancers from lifetime nonsmokers (19%) and ex-smokers (67%; odds ratio, 9.08; 95% confidence interval, 2.06-39.98). All deletions were found in tumors from patients who were either ex-smokers or nonsmokers exposed to passive smoking. The G:C to A:T transitions (11 of 28; 39%) were the most frequent p53 mutations found and clustered in tumors from lifetime nonsmokers without passive smoke exposure. The incidence of K-ras codon 12 or 13 mutations was 11% (14 of 115 analyzed) with no difference between long-term ex-smokers and nonsmokers. These and other results indicate that p53 mutations occur more commonly in smokers and ex-smokers than in never-smokers. Such comparisons provide additional evidence of genetic damage caused by tobacco smoke during lung carcinogenesis.