Lung cancer risk in families of nonsmoking probands: heterogeneity by age at diagnosis.

In an earlier investigation, we did not detect a major genetic component to lung cancer in families of nonsmoking lung cancer probands. However, heterogeneity with respect to familial aggregation, based on probands' age at diagnosis, was evident. We reanalyzed our previously collected data of 257 families, stratified by age at diagnosis of the probands, using complex segregation analysis. We specifically tested the effects of a Mendelian diallelic gene, history of tobacco use, and history of selected chronic lung diseases in families with a proband diagnosed at the age of 60 years or older and in families with a younger proband (i.e. , under 60 years of age). Cases were identified from the Metropolitan Detroit Cancer Surveillance System. Information on lung cancer occurrence, smoking history, and chronic respiratory diseases in first-degree relatives was obtained for 210 older probands and for 47 younger probands. In older probands' families, no evidence of a major genetic effect was detected. A history of emphysema and tobacco-smoke exposure were found to be significant risk factors. In younger probands' families, a Mendelian codominant model with significant modifying effects of smoking and chronic bronchitis best explained the observed data. Our results suggest the presence of a high-risk gene contributing to early-onset lung cancer in a population where the probands are nonsmokers.     

Health effects in underground uranium miners

The health effects associated with uranium miners have received much attention in the last 30 years. Although mortality rates are elevated for such causes as accidents and nonmalignant respiratory disease, lung cancer caused by exposure to radon decay products is the primary hazard to underground uranium miners. This review summarizes studies of eight cohorts of radium miners, and examines several pooled analyses that provide the best understanding of the radon/lung cancer relationship. The relative risk of lung cancer is linearly related to cumulative exposure to radon decay products. The excess relative risk decreases with attained age and time since exposure. An inverse exposure-rate effect exists, such that prolonged exposure at low levels of radon is more hazardous than shorter exposures to higher levels. The linear no-threshold model used in most epidemiologic studies has been attacked by some as overestimating risk at indoor radon levels. These arguments are rejected by this reviewer.     

Lung cancer risk among former uranium miners of the WISMUT Company in Germany

After 1946, the WISMUT Company developed the third-largest uranium-mining province in the world in the German Democratic Republic. METHODS: A case-control study among former WISMUT miners was conducted to investigate the lung cancer risk in relation to attained age, time since exposure, exposure duration, and exposure rate. It consisted of 505 patients with lung cancer and 1,073 controls matched to cases according to the year of birth. The cumulative exposure to radon and radon decay products was calculated as the sum of yearly exposures and expressed in Working Level Months (WLM). Cases had a mean cumulative exposure of 552 WLM compared to 420 WLM in controls. RESULTS: There was a statistically significant increase in lung cancer risk for cumulative exposures above 800 WLM. Under the assumption of a linear risk model, there was a significant increase in the relative risk of 0.10 per 100 WLM after adjusting for smoking and asbestos exposure. For current smokers the increase in relative risk was lower (0.05 per 100 WLM), whereas it was higher (0.20 per 100 WLM) among nonsmokers and longtime ex-smokers. After correcting in a sensitivity analysis for the fact that the controls of this study had a higher average exposure than the population of WISMUT workers they were recruited from, the adjusted ERR increased to 0.24 per 100 WLM. Lung cancer risk declined with time since exposure, except for exposures received 45 or more years ago. No inverse dose rate effect was observed.     

Lung cancer and indoor air pollution arising from Chinese-style cooking among nonsmoking women living in Shanghai, China.

Associations between indoor air pollution from Chinese-style cooking and lung cancer have been found in several investigations. To provide more detailed estimates of the associations while accounting for key confounding factors, we conducted a population-based, case-control study of lung cancer among nonsmoking women living in Shanghai, the People's Republic of China. Five hundred four incident, primary lung cancer cases diagnosed from February 1992 through January 1994 were identified through the population-based Shanghai Cancer Registry. A control group of 601 nonsmoking women was selected randomly from the Shanghai-Residential Registry, and they were frequency-matched to the expected age distribution of the cases. Exposure to indoor air pollutants from Chinese-style cooking was ascertained through in-person interviews. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression. There were similar patterns of excess risk for exposure to indoor air pollutants from Chinese-style cooking across different histological types of lung cancer. Women who did not have a separate kitchen experienced a 28% increased risk of lung cancer (OR = 1.28; 95% CI = 0.98-1.68). We found little association with area of the windows of the apartment where subjects had lived for the longest period of time. Heating cooking oils to high temperatures was associated with a 1.64-fold increased risk of lung cancer (95% CI = 1.24-2.17). An 84% excess risk was found among women who most often cooked with rapeseed oil (OR = 1.84; 95% CI = 1.12-3.02). Lung cancer risks were also related to "considerable" smokiness of the kitchen during cooking (OR = 2.38; 95% CI = 1.58-3.57), frequent eye irritation during cooking (OR = 1.68; 95% CI = 1.02-2.78), to a more than weekly use of frying (OR = 2.09; 95% CI = 1.14-3.84) and deep-frying (OR = 1.88; 95% CI = 1.06-3.32). This population-based case-control study confirmed that exposure to indoor air pollution from Chinese-style cooking, especially cooking unrefined rapeseed oil at high temperatures in woks, may increase the risk of lung cancer.     

Passive smoking and lung cancer in nonsmoking women.

OBJECTIVES. The causes of lung cancer among nonsmokers are not clearly understood. To further evaluate the relation between passive smoke exposure and lung cancer in nonsmoking women, we conducted a population-based, case-control study. METHODS. Case patients (n = 618), identified through the Missouri Cancer Registry for the period 1986 through 1991, included 432 lifetime nonsmokers and 186 ex-smokers who had stopped at least 15 years before diagnosis or who had smoked for less than 1 pack-year. Control subjects (n = 1402) were selected from driver's license and Medicare files. RESULTS. No increased risk of lung cancer was associated with childhood passive smoke exposure. Adulthood analyses showed an increased lung cancer risk for lifetime nonsmokers with exposure of more than 40 pack-years from all household members (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.8) or from spouses only (OR = 1.3; 95% CI = 1.0, 1.7). When the time-weighted product of pack-years and average hours exposed per day was considered, a 30% excess risk was shown at the highest quartile of exposure among lifetime nonsmokers. CONCLUSIONS. Ours and other recent studies suggest a small but consistent increased risk of lung cancer from passive smoking. Comprehensive actions to limit smoking in public places and worksites are well-advised.     

Lung cancer risk associated to exposure to radon and smoking in a case-control study of French uranium miners

A case-control study nested in the cohort of French uranium miners took smoking information into account in investigating the effect of radon exposure on lung cancer risk. This study included 100 miners who died of lung cancer and 500 controls matched for birth period and attained age. Data about radon exposure came from the cohort study, and smoking information was retrospectively determined from a questionnaire and occupational medical records. Smoking status (never vs. ever) was reconstructed for 62 cases and 320 controls. Statistical analyses used conditional logistic regression. The effect of radon exposure on lung cancer risk was assessed with a linear excess relative risk model, and smoking was considered as a multiplicative factor. Mean cumulative radon exposures were 114.75 and 70.84 Working Level Months (WLM) among exposed cases and controls, respectively. The crude excess risk of lung cancer per 100 WLM was 0.98 (95% CI: 0.18-3.08%). When adjusted for smoking, the excess risk was 0.85 per 100 WLM (95% CI: 0.12-2.79%), which is still statistically significant. The relative risk related to smoking was equal to 3.04 (95% CI: 1.20-7.70). This analysis shows a relative risk of lung cancer related to smoking similar to that estimated from previous miners' cohorts. After adjustment for smoking, the effect of radon exposure on lung cancer risk persists, and its estimated risk coefficient is close to that found in the French cohort without smoking information.     

Increased cancer risk among relatives of nonsmoking lung cancer cases

Lung cancer has been shown to aggregate in families of nonsmoking lung cancer cases with an earlier age at onset. The current study evaluates whether relatives of nonsmoking lung cancer cases are at increased risk of cancers at sites other than lung. Families were identified through 257 population‐based, nonsmoking lung cancer cases and 277 population‐based, nonsmoking controls residing in metropolitan Detroit. Data were collected for 2,252 relatives of cases and 2,408 relatives of controls. First‐degree relatives of nonsmoking lung cancer cases were at 1.52‐fold (95% CI, 1.02–2.27) increased risk of cancer of the digestive system after adjustment for each relative's age, race, sex, and smoking status. Relative risk estimates also were elevated, but not significantly, for tobacco‐related cancers (RR = 1.39) and breast cancer (RR = 1.72). Among first‐degree relatives of younger probands (age 40–59), risk was non‐significantly increased 72% (95% CI 0.95–3.10) for all cancers combined and 3.14‐fold for cancers of the digestive system (95% CI 0.76–12.9). Nonsmoking relatives of cases were at increased risk of all cancer sites combined (RR = 1.32; 95% CI 1.003–1.73), cancers other than lung (RR = 1.37; 95% CI 1.03–1.82), and digestive system cancers (RR = 2.01; 95% CI 1.20–3.37). These findings of moderate familial aggregation for cancers of the lung, digestive system, breast, and tobacco‐related sites suggest that common susceptibility genes may act to increase risk for a variety of cancers in families. Genet. Epidemiol. 17:1–15, 1999. © 1999 Wiley‐Liss, Inc.     

人乳头瘤病毒感染与非吸烟女性肺癌关系

目的 探讨人乳头瘤病毒(HPV)感染与非吸烟女性肺癌的相关性,以及HPV感染对脆性组氨酸三联体(FHIT)基因杂合性丢失的影响.方法 采用1:1匹配的病例对照研究方法,应用PCR技术检测肺癌组织与对照组织中HPV-DNA相关序列,同时检测FHIT基因杂合性丢失状况.结果 肺癌组织HPV-E6检出率高于对照组,OR=3.500,高危型HPV感染肺组织中FHIT基因杂合子丢失率较高.同时HPV感染与口服避孕药的使用、烹调油烟暴露及既往肺部疾病史间存在交互作用.结论 高危型HPV感染与女性肺癌的发生有关,HPV感染引发的肺癌可能与基因整合使FHIT基因杂合性丢失有关,同时与口服避孕药的使用、烹调油烟暴露及既往肺部疾病史等存在协同效应.     

Genetic analysis of families with nonsmoking lung cancer probands

As part of a genetic epidemiologic study of lung cancer among nonsmokers, we investigated the role of genetic predisposition in familial aggregation. Cases were identified from the Metropolitan Detroit Cancer Surveillance System. Information on lung cancer occurrence, smoking habits (active or passive), and chronic respiratory diseases in first-degree relatives was obtained for 257 nonsmoking lung cancer probands (71 males, 186 females) diagnosed at ages 40–84 years. Among the 2,021 first-degree relatives, 24 (2.6%) males and 10 (1.1%) females were reported as having lung cancer. The occurrence of lung cancer among smoking and nonsmoking relatives was 4.5% and 1.1% in males and 2.8% and 0.4% in females, respectively. To evaluate the role of a putative Mendelian gene (one locus, two alleles) in the presence of other risk factors, we performed complex segregation analyses on the data using two different regressive model approaches [Segregation Analysis of a Discrete Trait Under a Class A Regressive Logistic Model, V4.0 (REGD) and Segregation Analysis of a Truncated Trait, V2.0, Model I (REGTL)] as implemented in the Statistical Analysis for Genetic Epidemiology (SAGE) program. Using either approach, an environmental model best explained the observed lung cancer aggregation in families ascertained through nonsmoking probands. Based on our final model, only 0.04% of this population had a very high risk and 4.2% had a moderate risk of lung cancer. The rest of the population had virtually no risk of lung cancer during their lifetime unless they have multiple risk factors. Among the high-risk individuals without any risk factor under study, the estimated risks at ages 40,60, and 80 years in males were 16.7%, 83.6%, and 95.4%, and in females were 14.0%, 72.2%, and 88.0%, respectively. Among at-moderate-risk smokers the estimated risks at the same age and gender groups were essentially the same as in the high-risk nonsmokers. Our results suggest that the pattern of lung cancer occurrence in families of nonsmoking lung cancer patients differs from that in families of smoking lung cancer patients. Despite the profound effect of smoking on the risk of lung cancer, other environmental and/or genetic risk factors need to be identified. Genet. Epidemiol. 14:181–197,1997. © 1997 Wiley-Liss, Inc.     

Mortality in a Chinese chrysotile miner cohort

Background  

Few data were available to address cause-specific mortality in asbestos miners in China. This study observed a cohort of workers from the largest chrysotile asbestos mine to evaluate the association between asbestos exposure and cause-specific mortality.     

Practical difficulties in determining 222Rn flux density in underground uranium mines

Radon-222 flux density, J, has been determined in a number of locations in an underground U mine. Measurements were conducted using the Two-Point Measurement (2PM) method, consisting of measuring the 222Rn concentration at two different points a distance apart within a given section of the mine. Several mine models were used for determining J by the above method. The 2PM method is sensitive to sources and sinks of 222Rn other than mine walls, as well as mining operations and mining activities of a diverse nature, and to local variations in airflow conditions. Because of this, J obtained by the 2PM method represents an "apparent" flux density. Significant differences were found in the flux density calculated according to different mine models. In addition, J measurements using the flux "can" method were also carried out in mine walls and compared with the values obtained by the 2PM method. Wide discrepancies between the two methods were found. The practical and theoretical difficulties in determining J are discussed.     

Preexisting lung disease and lung cancer among nonsmoking women.

Preexisting lung disease was examined as a risk factor for lung cancer in a population-based, case-control study of nonsmoking women in Missouri conducted between June 1, 1986, and April 1, 1991. A history of lung disease was reported by approximately 41% of 618 cases and 35% of 1,402 controls (odds ratio (OR) = 1.2; 95% confidence interval (Cl) 1.0-1.5. The risk was more pronounced when next-of-kin interviews were excluded (OR = 1.5). Previous lung disease was significantly related both to adenocarcinoma (OR = 1.4), which accounted for 62% of the cancers, and to all other cell types of lung cancer combined (OR = 1.8). Despite having discontinued smoking for more than 15 years, long-term ex-smokers were at a 2.2-fold risk of lung cancer compared with lifetime nonsmokers. Among lifetime nonsmokers, significant risks were noted for asthma (OR = 2.7) and pneumonia (OR = 1.5). Emphysema (OR = 2.6) and tuberculosis (OR = 2.0) were also significantly related to lung cancer, but only among former smokers. Chronic bronchitis was linked to elevated risks of nonadenocarcinomas only (OR = 2.3). Pleurisy was not reported more frequently by cases than by controls. Approximately 16% of all lung cancers among nonsmoking women could be attributed to previous lung diseases, most notably asthma, pneumonia, emphysema, and tuberculosis.     

Lung cancer in workers in a nickel refinery

ABSTRACT This study is an analysis of the occurrence of lung cancer in nickel workers, particularly with regard to development time, histological types and tobacco smoking, in addition to specific exposure to nickel dust and fumes. It is a continuation of previous work in this field (Kreyberg, 1954a, b; 1962, 1969). The series consists of 44 cases of lung cancer occurring during the years 1948-74 in people currently or previously employed at Falconbridge nickel refinery. A seven-year period of reduced activity during the war enables lung cancer in workers who took up employment in 1927-39 to be compared with that in workers who started in or after 1946. It is confirmed that exposure to nickel dust and fumes increases the risk of developing lung cancer. However, all subjects with small cell anaplastic carcinoma and at least 25 out of 28 subjects with epidermoid carcinoma had been tobacco smokers. Four smokers and four non-smokers had Group II tumours. The mean age at diagnosis of lung cancer in the nickel workers corresponds closely with that of male subjects with lung cancer in general, in spite of the very wide differences in the development time, if this is related to the employment time in the refinery alone. The mean age at diagnosis is, however, consistent if the development time is related to the length of tobacco smoking. Tobacco smoking is an important factor in the development of lung cancer in nickel workers, and under the conditions described in this study the reduced carcinogenic influence may be attributable to reduced exposure to nickel and possibly also to tobacco.