Case-control Study Of Lung Cancer Research Articles

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers.

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S-transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH-DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09-8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.

Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe.

An association between exposure to environmental tobacco smoke (ETS) and lung cancer risk has been suggested. To evaluate this possible association better, researchers need more precise estimates of risk, the relative contribution of different sources of ETS, and the effect of ETS exposure on different histologic types of lung cancer. To address these issues, we have conducted a case-control study of lung cancer and exposure to ETS in 12 centers from seven European countries. A total of 650 patients with lung cancer and 1542 control subjects up to 74 years of age were interviewed about exposure to ETS. Neither case subjects nor control subjects had smoked more than 400 cigarettes in their lifetime. ETS exposure during childhood was not associated with an increased risk of lung cancer (odds ratio [OR] for ever exposure = 0.78; 95% confidence interval [CI] = 0.64-0.96). The OR for ever exposure to spousal ETS was 1.16 (95% CI = 0.93-1.44). No clear dose-response relationship could be demonstrated for cumulative spousal ETS exposure. The OR for ever exposure to workplace ETS was 1.17 (95% CI = 0.94-1.45), with possible evidence of increasing risk for increasing duration of exposure. No increase in risk was detected in subjects whose exposure to spousal or workplace ETS ended more than 15 years earlier. Ever exposure to ETS from other sources was not associated with lung cancer risk. Risks from combined exposure to spousal and workplace ETS were higher for squamous cell carcinoma and small-cell carcinoma than for adenocarcinoma, but the differences were not statistically significant. Our results indicate no association between childhood exposure to ETS and lung cancer risk. We did find weak evidence of a dose-response relationship between risk of lung cancer and exposure to spousal and workplace ETS. There was no detectable risk after cessation of exposure.

Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer.

Machining fluids are diverse products that contain numerous additives and contaminants, including polycyclic aromatic hydrocarbons. Studies treating machining fluids as an aggregate exposure have found both positive and negative associations with lung cancer. In this nested case-control study of automotive workers (667 cases and 3,041 matched controls), individual estimates of exposure quantity and duration for specific classes of machining fluids were derived. An inverse dose-response relationship was found between synthetic machining fluids and lung cancer mortality, with an odds ratio of 0.6 (95% CI = 0.4, 0.8) for the highest level of lifetime exposure. The relationship was strongest for recent exposures. There was little evidence of an association with soluble or straight oil machining fluids. Risks were inconsistently elevated in workers exposed to aluminum. Results from this study provide strong evidence that exposure to machining fluids is not associated with an increased risk of lung cancer mortality in automotive workers.

A case-control study of lung cancer at a foundry and two engine plants.

A nested case-control study of lung cancer was conducted among workers at an iron foundry and two engine manufacturing plants whose lung cancer mortality rates were slightly higher than expected. The study included 231 lung cancer cases and 408 controls for whom complete work histories were obtained. There was no association between usual plant of employment and lung cancer mortality. The odds ratio for persons employed for 20 or more years in the foundry compared with persons employed in the engine plants was 0.90 (95% confidence interval: 0.55, 1.5). Long-term employment as an engine plant worker was associated with odds ratios slightly, but not statistically significantly, below unity. In the foundry, only usual employment in the material handling departmental group and any employment in the quality control departmental group were statistically significantly directly related to lung cancer risk. However, the number of subjects so employed was small and there was no dose-response relation between length of employment in these departmental groups and lung cancer risk. Cases were less frequently employed than were controls in engine plant machining and assembly jobs and departments. It is concluded that employment in this facility was either unrelated, or only weakly related, to lung cancer risk.

Chromosome 13 poly(ADP-ribose) polymerase polymorphisms and lung cancer risk

A 193 base pair repeat polymorphism in the human poly(ADP-ribose) polymerase (PADPRP) pseudogene found on chromosome 13 has been associated with lung cancer, endemic Burkitt lymphoma, B-cell lymphoma, breast cancer and colorectal carcinoma. We investigated the frequency of the PADPRP genetic polymorphism in a hospital-based case-control study of lung cancer for 54 cases and 47 controls. There was a statistically significant difference in allelic frequency between Caucasians and African Americans (p<0.001). For African Americans, the odds ratio for lung cancer and the 'B' allele was 2.38 (95% C.I.=0.73, 7.69) and for Caucasians 0.44 (95% C.I.=0.11, 1.77). The results for the African Americans, however, were not in Hardy-Weinberg equilibrium, although the Caucasians were. Thus, this study, albeit small, does not find that the PADPRP pseudogene duplicated region located on chromosome 13 is a risk factor for lung cancer.

Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer

Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer

Radon measurements in underground dwellings from two prefectures in China.

Radon, an established lung carcinogen, remains the single most important environmental radiation exposure. Yet, an excess of lung cancer from breathing radon in homes has not been consistently demonstrated in studies conducted to date. To address several major problems that have hindered previous studies of lung cancer and radon in homes, we have embarked upon a lung cancer case-control study in Gansu Province, China, where a substantial proportion of the population live in underground dwellings. In this paper, we report on results of a pilot study in which radon measurements were made for 3 days in the summer in 40 homes under normal occupancy conditions using short-term E-PERM detectors and for 6 months from February through August in 49 homes using long-term alpha-track detectors. Useable E-PERM data were obtained from 38 homes and useable alpha-track data from 47 homes. For both types of detectors, measurements were approximately log-normally distributed. Arithmetic and geometric means were 233 and 185 Bq m-3 (range 74-1,590 Bq m-3) for E-PERM measurements and 165 and 158 Bq m-3 (range 74-592 Bq m-3) for alpha-track measurements, respectively; 68% of E-PERM measured homes and 55% of alpha-track measured homes exceeded 148 Bq m-3. Alpha-track measurements made at the entry, middle, and rear areas of the underground dwellings did not differ significantly (arithmetic means of 168, 162, and 165 Bq m-3 with standard deviations 63, 73, and 48, respectively), which suggests that air circulation may be minimal. The underground dwellings measured in the pilot study had high radon levels and the underground dwellers may provide an excellent population for studying indoor radon and risk of lung cancer.

Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer

A clonal assay to determine the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase ( hprt) locus in human lymphocytes has been used by a number of investigators to study exposure to mutagens and carcinogens in a variety of populations. We have studied hprt MF in 106 subjects (40 controls and 66 cases) enrolled in a case-control investigation of lung cancer. Epidemiological data collected included smoking history, intake of dietary micronutrients, and occupational and environmental exposures as well as medical history, all obtained from an interviewer-administered questionnaire. All subjects were also genotyped for the known polymorphism in glutathione S-transferase class mu (GST-mu). In analysis of cases and controls, hprt MF was not associated with age, smoking, the polymorphism in GST mu, dietary intake, occupational exposures, family history of cancer or usage of medications. Since MF and cloning efficiency (CE) are not independent when CE is low, further analysis in cases and controls with a CE greater than or equal to 30% (27 cases and 22 controls) was also conducted. In analysis of controls, hprt MF increased with age and was inversely associated with intake of folate and vitamins A and C. The presence of lung cancer was not associated with hprt MF. Thus, our study supports the previous observation that dietary components may affect the MF at the hprt locus.

Is Chinese Incense Smoke Hazardous to Respiratory Health?

Incense is a common source of indoor air pollution, especially in Asian homes where it is burned for religious reasons. In previous studies in Hong Kong, it was found to be the major source of airborne carcinogens in the home, and a significant contributor to personal exposures to nitrogen dioxide among wom en. To evaluate its effects on respiratory health, data from an air pollution cross-sectional study of 346 primary school children and their 293 non-smok ing mothers, and a lung cancer case-control study of 189 female patients and 197 district matched controls who had ever been married were analysed. No association was found between exposure to incense burning and respiratory symptoms like chronic cough, chronic sputum, chronic bronchitis, runny nose, wheezing, asthma, allergic rhinitis, or pneumonia among the three popu lations studied: i.e. primary school children, their non-smoking mothers, or a group of older non-smoking female controls. Incense burning did not affect lung cancer risk among non-smo...

Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls

Cytogenetic alterations have been associated with the occurrence of many cancers. However, limited data exist to address whether increased chromosomal changes in surrogate normal tissue are similarly associated with malignancy. As part of an ongoing case-control study of lung cancer, we have studied the factors that affect sister chromatid exchange (SCE) frequency in lymphocytes from lung cancer patients. Further, we sought to investigate whether the factors that affect SCE frequencies were comparable in lung cancer cancer cases and controls. Cases had newly diagnosed, operable primary lung cancer. Controls were friends and spouses of cases. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was obtained in an interviewer-administered questionnaire. Intake of antioxidants was also determined through the administration of a validated semiquantitative food frequency questionnaire. Metabolic traits studied included the polymorphic glutathione-S-transferase class mu (GST-mu) and variants of P450 isoenzymes CYP1A1 and CYP 2D6. Overall, 78 cases and 78 controls were included in the analysis. Although there was a small number of lung cancer patients who had never smoked in the study (9% of cases), these patients had higher SCE frequencies than current or former smokers. This suggests that factors associated with genomic instability may also play a role in the pathogenesis of lunc cancer. The best fit model for SCE frequency, which had been previously generated from control data alone, included age, gender, smoking, GST-mu, and vitamin A intake. However, when this model was applied to lung cancer patients, smoking was not associated with an elevated SCE frequency. Thus, it is not clear that SCE frequency data in prevalent lung cancer cases and controls are comparable.

An ecological study of diet and lung cancer in the South Pacific.

Incidence rates of lung cancer have been markedly lower for Fiji than for other South Pacific countries, despite similar rates of smoking. We conducted population-based surveys in several island nations of the South Pacific (Cook Islands, Fiji, Tahiti and New Caledonia) and used data from Caucasian, Japanese, Hawaiian, Filipino and Chinese controls in a case-control study of lung cancer in Hawaii to investigate the role of diet in explaining differences in lung cancer incidence among 20 ethnic-sex groups. In a stepwise linear regression of lung cancer rates on smoking, diet and other variables, smoking, as expected, explained the majority (61%) of the variability in incidence. However, several dietary components also explained significant portions of the variance. Lutein intake explained 14% and vitamin E intake, cholesterol intake and height explained 5-7% each of the remaining variance in incidence. Associations with lutein and vitamin E were inverse, whereas those with cholesterol and height were direct. Dietary beta-carotene intake was not associated with lung cancer incidence. These ecological data provide evidence for a protective effect of lutein against lung cancer. A protective effect of dietary vitamin E and a risk-enhancing effect of dietary cholesterol are also suggested.

Urinary nicotine metabolite excretion and lung cancer risk in a female cohort.

A nested lung cancer case-control study was carried out using 397 12 h urine samples originally collected from a cohort of over 26,000 women aged 40-64 at entry who were then followed for up to 15 years. The urine samples from active smokers were first identified using a simple qualitative method and their total nicotine metabolites/creatinine ratios then determined by automated colorimetric methods. The results obtained demonstrated the capacity of nicotine metabolite estimations in a single 12 h sample of urine to predict the subsequent risk of lung cancer. The risk of lung cancer among the biochemically proven active smokers during this period was 7.8 times that of the non-smokers, suggesting that the dose-response relationship between smoking and lung cancer is no less step in women than in men. The smoking-related risk of adenocarcinoma was less than that of other lung carcinomas. It is suggested that this biochemical epidemiology approach to exploring the relationship between smoking and lung cancer could profitably be applied to the study of other smoking-related diseases.

Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States.

The authors conducted a population-based case-control study of lung cancer in nonsmoking women in five metropolitan areas of the United States between December 1, 1985, and November 30, 1990. In-person interviews were conducted with 412 lung cancer cases and 1,253 population controls, yielding information on history of nonmalignant lung diseases that were diagnosed by a physician. When lung cancer cases were compared with controls, history of any previous lung disease was associated with a significant increased risk of lung cancer (adjusted odds ratio (AOR) = 1.56, 95% confidence interval (CI) 1.2-2.0). Several lung diseases, including asthma, chronic bronchitis, pneumonia, and tuberculosis, were reported more often by lung cancer cases than by controls, and the difference was statistically significant for asthma (AOR = 1.67, 95% CI 1.1-2.5) and chronic bronchitis (AOR = 1.60, 95% CI 1.1-2.4). Since significant increased risks were observed for asthma and tuberculosis diagnosed before age 21 years, it is unlikely that reported prior lung diseases were prediagnostic manifestations of lung cancers. The increased risks associated with previous lung disease were observed for adenocarcinomas and other carcinomas of the lung; the point estimates were generally higher for the latter category. The risks associated with previous lung diseases remained unchanged after adjustment for potential confounders, including environmental tobacco smoke exposure during childhood and adult life and dietary factors.

Mortality of iron foundry workers. III. Lung cancer case-control study: Andjelkovich DA, Shy CM, Brown MH, Janszen DB, Levine RJ, Richardson RB. Chemical Industry Toxicology Inst., P.O. Box 12137, Research Triangle Park, NC 27709. J. Occup Med 1994; 36: 1301–1309

Mortality of iron foundry workers. III. Lung cancer case-control study: Andjelkovich DA, Shy CM, Brown MH, Janszen DB, Levine RJ, Richardson RB. Chemical Industry Toxicology Inst., P.O. Box 12137, Research Triangle Park, NC 27709. J. Occup Med 1994; 36: 1301–1309

Analysis of cytochrome P450 2E1 genetic polymorphisms in relation to human lung cancer: Kato S, Shields PG, Caporaso NE, Sugimura H, Trivers GE, Tucker MA et al. Laboratory of Human Carcinogenesis, Division of Etiology, National Cancer Institute, Bethesda, MD 20892. Cancer Epidemiol Biomarkers Prev 1994;3:515–518

Human cancer risk assessment using molecular genetic techniques is a rapidly emerging field. Many studies suggest that both inherited and acquired genetic predispositions play an important role in carcinogenesis. Cytochrome P450 (CYP) 2E1 is involved in the metabolic activation of N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2E1 [DraI restriction fragment length polymorphism (RFLP)] has been associated with an increased risk of lung cancer in Japanese. We have assessed the allelic frequency of three RFLPs (PstI, RsaI, and DraI) in African-Americans (n = 109), Caucasian Americans (n = 153), and octogenarian Japanese (n = 42), and also in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2E1 DraI polymorphism to other CYP2E1 polymorphisms (PstI and RsaI RFLP) was examined. The allelic frequency of the DraI C minor allele for all subjects was 0.09 in Caucasians, 0.09 in African-Americans, and 0.31 in Japanese. In the case-control study of lung cancer, no association of the CYP2E1 DraI genotype with lung cancer was found (odds ratio, 1.57; 95% confidence interval, 0.59-4.18). Comparison after discordant CYP2E1 genotypes suggests the presence of different haplotypes in Americans and Japanese. These results indicate that the CYP2E1 DraI RFLP is probably not a cancer risk factor in United States Caucasian or African-Americans, although statistical power is limited given the low frequency of the CYP2E1 DraI C minor alleles.

Cohort mortality and nested case-control study of lung cancer among structural pest control workers in Florida (United States): Pesatori AC, Sontag JM, Lubin JH, Consonni D, Blair A. National Cancer Institute, Executive Plaza North, Rockville, MD 20892. Cancer Causes Conrol 1994;5:310–318

Cohort mortality and nested case-control study of lung cancer among structural pest control workers in Florida (United States): Pesatori AC, Sontag JM, Lubin JH, Consonni D, Blair A. National Cancer Institute, Executive Plaza North, Rockville, MD 20892. Cancer Causes Conrol 1994;5:310–318

Lung cancer in nonsmoking women. Histology and survival patterns

Despite the widespread view that important clinical and etiologic differences exist between histologic categories of lung cancer, few studies have examined the accuracy of hospital-reported pathologic diagnoses of lung cancer. A review of pathologic material and an assessment of survival patterns were conducted in conjunction with a recently completed case-control study of lung cancer among nonsmoking women in Missouri. Using established protocols, tissue slides from tumors of 482 patients were reviewed by 3 pathologists. Adenocarcinoma was the most common histologic type among former smokers and lifetime nonsmokers. The overall agreement rate between the original and review diagnoses was 65.6%. The positive predictive value ranged from 0.33 for bronchioalveolar carcinomas to 0.84 for adenocarcinomas. Agreement rates for small, medium, and large hospitals were 63.1, 66.6, and 66.2%, respectively. Survival rates were highest for bronchioalveolar carcinoma and lowest for small cell carcinoma. Given the importance of lung cancer to public health and the need to examine risk by histologic type, these data indicate that pathologic review of registry-reported lung cancer cases may be an important component of large scale studies of etiology.

Lung cancer pathology in smokers, ex-smokers and never smokers.

The histologic distribution of lung cancer is markedly different in smokers and non-smokers. It is not known whether the histology among former smokers varies according to the number of years since quitting. Using data from a large case-control study of lung cancer, we found that for both men and women, the proportion of adenocarcinomas increased with the number of years since quitting smoking. Among long-term quitters (> 25 years), the proportion of adenocarcinomas was similar to that in never smokers. These findings have implications for studies of environmental tobacco smoke and lung cancer.

Occupational associations with lung cancer in two Ontario cities.

A death certificate based case-control study of lung cancer in two Ontario cities was performed to estimate the risk of lung cancer attributable to occupation in Ontario, and to estimate the proportion of occupational lung cancers receiving compensation from the Workers' Compensation Board. Occupation and industry were identified from the death certificate. A priori occupations for analysis were those whose members had received compensation for occupational cancer from the Ontario Workers' Compensation Board. Population attributable risks were computed using the relative risks observed in this study and employment data from the 1986 Census of Canada. Subjects were all men (N = 967) between the ages of 45 and 75 years resident in the cities of Hamilton and Sault Ste-Marie who died of lung cancer from 1979 to 1988. Controls (2,821) were matched on age, year of death, and city of residence. In agreement with other studies, an increased risk of lung cancer was observed for workers in the construction sector, for miners, and for truck drivers. It was estimated that only a small proportion of lung cancers attributable to occupation are compensated in Ontario. It is believed that many occupational cancers go uncompensated because of the failure to file claims, rather than because claims are rejected by Compensation Boards. Physicians are in a position to advise patients about the possibility of compensable disease and to act as advocates for them. By recognizing compensable illness, physicians have the opportunity to ease the financial burden of patients and their families. The challenge is a difficult one, but it is well worth pursuing.

Is Chinese Incense Smoke Hazardous to Respiratory Health?

Incense is a common source of indoor air pollution, especially in Asian homes where it is burned for religious reasons. In previous studies in Hong Kong, it was found to be the major source of airborne carcinogens in the home, and a significant contributor to personal exposures to nitrogen dioxide among women. To evaluate its effects on respiratory health, data from an air pollution cross-sectional study of 346 primary school children and their 293 non-smoking mothers, and a lung cancer case-control study of 189 female patients and 197 district matched controls who had ever been married were analysed. No association was found between exposure to incense burning and respiratory symptoms like chronic cough, chronic sputum, chronic bronchitis, runny nose, wheezing, asthma, allergic rhinitis, or pneumonia among the three populations studied; i.e. primary school children, their non-smoking mothers, or a group of older non-smoking female controls. Incense burning did not affect lung cancer risk among non-smokers, but it significantly reduced risk among smokers, even after adjusting for lifetime smoking amount. A possible explanation for this unexpected finding is that incense burning was associated with certain dietary habits, i.e. more fresh fish, more retinol, and less alcohol, which have been associated with lower lung cancer risk in this population. These results indicate that diet can be a significant confounder of epidemiological studies on air pollution and respiratory health.