Smoking and the molecular epidemiology of lung cancer

Lung carcinogenesis in humans requires exposure to environmental agents, including the inhalation of tobacco smoke, radioactive compounds, asbestos, heavy metals, and petrochemicals. Tobacco smoking is the risk factor with the highest attributable lung cancer risk worldwide. This article discusses occupational carcinogen exposure and exposure from tobacco use, and the lung-cancer risk associated with these types of exposure.     

Smoking and cardiac symptoms as predictors of lung cancer

In 1962, a cohort of 4604 Finnish men was interviewed about their smoking habits and cardiorespiratory symptoms. The cohort was followed up for deaths and incidence of lung cancer from 1963 to 1980 in order to study the effect of smoking and cardiac symptoms on the incidence of lung cancer. When analyzed simultaneously with smoking, the symptoms of angina, possible infarction and shortness of breath were all significantly associated with increased lung cancer risk. For example, the RR of lung cancer among those with possible infarction was 2.4, when age and smoking were adjusted for, and 1.8, when additionally shortness of breath and angina-like chest pain were adjusted for. Among smokers of greater than or equal to 15 g/day, those with symptoms of angina displayed a considerable excess risk (RR 2.5). A broad range of impairments of the cardiopulmonary functions seem to be associated with the carcinogenic processes invoked by smoking.     

Smoking and effect of chemotherapy in small cell lung cancer

The relationship between smoking habits and outcome of treatment was studied in 154 patients with small cell lung cancer (SCLC) who received combination chemotherapy. Thirty-two patients had stopped smoking at least 6 months before the initiation of treatment or had never smoked (NS), 51 patients stopped smoking less than 6 months prior to the start of treatment (SS) and 71 patients continued to smoke during the treatment period (CS). Life table analysis of overall survival showed no significant heterogeneity among the groups (p greater than 0.7). Chi-square test for trend in survival yielded 0.23 (p greater than 0.6) with the longest survival in SS and CS patients, and the shortest survival in NS patients. Corresponding analysis of time to progression showed similar results, with a non-significant heterogeneity (p greater than 0.5) and trend (p greater than 0.4) among the three groups, with the CS patients doing best. In the whole series the disease-free two-year survival rate was higher in the CS patients than in the SS and NS patients (p = 0.04). The results do not imply that continued smoking during chemotherapy in SCLC has unfavourable effects on the outcome of treatment.     

Smoking and lung cancer survival: the role of comorbidity and treatment

STUDY OBJECTIVE: Numerous studies indicate that smoking is associated with poorer outcomes in patients with cancer. The aim of this study was to determine whether smoking independently predicts survival in patients with lung cancer or whether an existent effect is mediated through comorbidity and/or treatment. DESIGN AND SETTING: Cox proportional hazards analysis was used to study a cohort of 1,155 patients with lung cancer diagnosed at the Henry Ford Health System between 1995 and 1998, inclusive. RESULTS: Adjusted for the baseline covariates, age, gender, illicit drug use, adverse symptoms, histology, and stage, the hazard ratio (HR) for smoking (current vs former/never) was 1.37 (95% confidence interval [CI], 1.18 to 1.59; p < 0.001). Adjusted for the baseline covariates and for 18 deleterious comorbidities, the HR for smoking was 1.38 (95% CI, 1.18 to 1.60; p < 0.001), indicating that the hazardous effect of smoking was not mediated through comorbidity. Current smoking was inversely associated with treatment (any surgery and/or chemotherapy and/or radiation therapy vs none) [odds ratio, 0.73; 95% CI, 0.55 to 0.98 (p = 0.03)]. Adjusted for baseline covariates, comorbidities and treatment, the HR for current smoker vs former/never was 1.26 (95% CI, 1.08 to 1.47; p = 0.003), a decline of 30.7% explained by treatment (HR for any treatment vs none, 0.40; 95% CI, 0.33 to 0.48; p < 0.001). CONCLUSIONS: Current smoking at diagnosis is an important independent predictor of shortened lung cancer survival. That this effect was not explained by sociodemographic/exposure factors, adverse symptoms, histology, stage, comorbidity, and treatment suggests that it may be mediated through direct biological effects.     

Smoking, lung function, and rheumatoid factors.

Positive rheumatoid factor (RF) reactions commonly precede the onset of clinically manifest rheumatoid arthritis (RA). Thus if items associated with RF reactions were traced at the community level this might provide clues to the cause of RA. The relations between smoking and lung functions and the occurrence of RA and RFs in a population sample representative of the adult Finnish population were studied. Rheumatoid factor testing was performed for 7124 subjects (89% of the sample) by the sensitised sheep cell agglutination test. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured with spirometry. 'False positive' RF reactions occurred twice as often in current smokers and ex-smokers than in those who had never smoked. The prevalence of high titres was fourfold greater among current smokers than among those who had never smoked. These associations were statistically significant and independent of age, FVC, and FEV1 in both sexes. The women with airflow limitation (FEV1/FVC less than 70%) had a significantly increased occurrence of RFs which was independent of their smoking history, but no such relationship was found in men. The results suggest an impact of smoking on RF production; a follow up study may show whether the raised RF titers in smokers will be reflected as an increased incidence of RA.     

Smoking and smoking cessation in cancer patients

Persons with malignant disease have been a neglected population for research in smoking cessation. Besides the well-established role of cigarette smoking in the development of several types of cancers, there are numerous adverse health consequences of continued smoking for the diagnosed cancer patient. These include: increased risk of further neoplasms, poorer survival, and complications of surgery, radiation and chemotherapy; risk of non-neoplastic smoking-related diseases; and additional impairment of appetite and nutrition. Smoking prevalence at diagnosis is highest among patients with smoking-related cancers. Prospective studies of a variety of cancer patient populations are needed to assess patterns of continued smoking and cessation. Systematic quit smoking programs should be integrated into cancer treatment regimens. Currently, two trials testing interventions delivered by medical providers are in progress. Important research issues concerning intervention in cancer patient smoking behavior include: identification of relevant target groups; definition of intervention style and content; delineation of dimensions of treatment; and documentation of beneficial effects. The growing number of long-term cancer survivors and the complications from other smoking-related diseases dictate that the smoking cessation needs of this population be addressed.     

Smoking cessation after diagnosis of lung cancer is associated with a beneficial effect on performance status

STUDY OBJECTIVE: To evaluate the impact of smoking history and postdiagnosis smoking cessation on performance status (PS) and survival in patients with lung cancer. DESIGN: Patients with non-small cell lung cancer (NSCLC) who were referred to our pulmonary laboratory for evaluation for surgical resectability between January and November 2001 were reviewed. We investigated the association between smoking status after diagnosis and survival, as well as the change in PS from the initial status to status at 6 and 12 months after the diagnosis was established. RESULTS: The records were reviewed for 206 patients, of whom 93 (45%) were current smokers, 15 (7%) were never-smokers, and 98 (48%) were former smokers. Among the 93 smokers, 46 quit and 47 continued smoking after the diagnosis. Disease stage, patient demographics, treatment modalities, and comorbidities were similar between these two groups. While there was no significant association between smoking status after diagnosis and patient survival, those who quit smoking maintained a better PS at 0 to 6 months (odds ratio [OR], 7.09; 95% confidence interval [CI], 1.99 to 25.3; p = 0.002) and at 0 to 12 months (OR, 6.99; 95% CI, 1.76 to 27.7; p = 0.006) than those who continued smoking after the adjustment for disease stage, patient demographics, treatment modalities, and comorbidities. CONCLUSION: Patients who quit smoking after the diagnosis of NSCLC maintained a better PS at 6 and 12 months regardless of disease stage, age, race, sex, therapy types, and comorbidities than those who continued to smoke.     

Smoking pattern of smokers with and without tobacco-smoke-related lung diseases

The number of cigarettes smoked, the duration of the smoking habit, and the tar content of the smoke influence the occurrence of tobacco-smoke-related lung diseases, as may also patterns of smoke inhalation. We therefore determined the smoking pattern, especially the time relation between cigarette puff and inhalation, in smokers with and without tobacco-smoke-related lung diseases. On the basis of clinical and radiologic findings as well as pulmonary function tests, 91 smokers were classified as smokers without lung disease, with small airway disease, with simple chronic bronchitis, with obstructive bronchitis, with pulmonary emphysema, and with lung cancer. Smoking and breathing patterns were recorded, using a smoke-flow machine and a strain-gauge belt while the subject smoked a cigarette. Blood levels of COHb were determined before and after smoking. Of the smoking characteristics assessed, puff-inhalation time, puff peak pressure, and the venous difference in COHb level before and after smoking varied significantly among the smoker groups. Puff-inhalation time, reflecting the duration of smoke retention in the mouth, was only 0.08 s (i.e., practically zero) in smokers with pulmonary emphysema and differed significantly from the time in the other groups. This puffing characteristic may be the consequence or the cause of emphysema. If the latter is true, smokers with emphysema may perhaps lack the acute airway response to smoke inhalation that normally protects most smokers from immediately inhaling tobacco smoke.     

间质性肺疾病与肺癌

间质性肺疾病(ILD)患者中肺癌的发病率增高,特别是特发性肺纤维化合并肺癌的报道最多.ILD合并肺癌的病理类型以鳞状细胞癌最多,好发于肺下叶和外周部位.ILD的一些肿瘤标记物增高,与疾病的活动程度、严重程度、肺纤维化程度和病情预后等有关,并且具有一定的诊断价值.ILD的肿瘤标记物增高可能是其合并肺癌的危险因素.本文对I...