Non-smoking Lung Cancer Cases Research Articles

Deciphering the impact of urban built environment density on respiratory health using a quasi-cohort analysis of 5495 non-smoking lung cancer cases

IntroductionLung cancer is a major health concern and is influenced by air pollution, which can be affected by the density of urban built environment. The spatiotemporal impact of urban density on lung cancer incidence remains unclear, especially at the sub-city level. We aimed to determine cumulative effect of community-level density attributes of the built environment on lung cancer incidence in high-density urban areas. MethodsWe selected 78 communities in the central city of Shanghai, China as the study site; communities included in the analysis had an averaged population density of 313 residents per hectare. Using data from the city cancer surveillance system, an age-period-cohort analysis of lung cancer incidence was performed over a five-year period (2009–2013), with a total of 5495 non-smoking/non-secondhand smoking exposure lung cancer cases. Community-level density measures included the density of road network, facilities, buildings, green spaces, and land use mixture. ResultsIn multivariate models, built environment density and the exposure time duration had an interactive effect on lung cancer incidence. Lung cancer incidence of birth cohorts was associated with road density and building coverage across communities, with a relative risk of 1·142 (95 % CI: 1·056–1·234, P = 0·001) and 1·090 (95 % CI: 1·053–1·128, P < 0·001) at the baseline year (2009), respectively. The relative risk increased exponentially with the exposure time duration. As for the change in lung cancer incidence over the five-year period, lung cancer incidence of birth cohorts tended to increase faster in communities with a higher road density and building coverage. ConclusionUrban planning policies that improve road network design and building layout could be important strategies to reduce lung cancer incidence in high-density urban areas.

Levels of Tobacco-specific Metabolites among Non-smoking Lung Cancer Cases at Diagnosis: Case-control Findings

Environmental tobacco smoking (ETS) significantly contributes to morbidity and mortality and is a known risk factor for lung cancer development in lifelong nonsmokers. The metabolite 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs) have now emerged as leading biomarkers for the study of carcinogen exposure in non-smokers exposed to ETS. We carried out our study on NNAL in the urine of non-smokers exposed to ETS and the association between ETS and lung cancer. Subjects were enrolled from 2008-2010. NNAL was analyzed for 74 non-smoking lung cancer and 85 healthy controls. The main objective of this study was to provide an estimate of the risk of lung cancer from exposure to ETS in the Korean population. The mean NNAL concentration in urine was significantly lower in non-smoking patient groups (n=74) than in control groups (n=85) (4.7±15.0 pg/mg, 6.5 ± 17.9 pg/mg, respectively, Mann-Whitney U test, p<0.001). The urine NNAL of non-smoking patients with lung cancer was not elevated with regard to the non-smoking control group. This may be due to life-style changes after diagnosis. A prospective study will be needed to evaluate the association of NNAL and non-smoking lung cancer.

A Pooled Analysis on the Associations between Involuntary Smoking and Lung Cancer Risk by Histological Types

Abstract Background: While the association between involuntary tobacco smoke exposure and lung cancer is well established, few studies with sufficient power have been conducted to evaluate the relationship between involuntary smoking (IS) and lung cancer by histological type, especially for the association between IS and small cell lung cancer among nonsmokers. Methods: We evaluated the associations between IS and lung cancer by histological type based on a pooled data of the International Lung Cancer Consortium (ILCCO). The individual-level epidemiological data from 17 participating studies were pooled, including 2,218 non-smoking lung cancer cases and 6,243 non-smoking controls. Logistic regression models were used to obtain adjusted odds ratios (OR) and 95% confidence intervals (CI), using SAS v9. Likelihood ratio tests were used to assess heterogeneity by study site. Results: Among never tobacco smokers, IS exposure was associated with lung cancer with an adjusted OR of 1.33 (95% CI 1.18, 1.50), compared to never exposure to IS, when adjusting for age, sex, ethnicity, and study site. Similar associations were observed in different histological types of lung cancer with adjusted ORs of 1.38 (95% CI 0.97, 1.98) for squamous cell carcinoma, 1.26 (95% CI 1.08, 1.46) for adenocarcinoma, 2.92 (95% CI 1.55, 5.48) for small cell lung cancer, and 1.30 (95% CI 1.14, 1.49) for non-small cell lung cancer. Similar associations with ever IS exposure were observed when the overall population including nonsmokers and smokers was included in the analysis. No apparent association was observed with IS exposure in childhood. Conclusion: This is the first study with a relatively large sample size investigating the relationship between IS exposure and small cell lung cancer among nonsmokers. Our results corroborated the association between IS and lung cancer regardless of histological types, including adenocarcinoma, and we observed the strongest association between IS and small cell lung cancer. Our study provides more precise estimates of the impact of IS on major histological types of lung cancer and suggests the importance of smoking intervention for lung cancer prevention, especially for small cell lung cancer type.

Polymorphisms in genes involved in the inflammatory response and interaction with NSAID use or smoking in relation to lung cancer risk in a prospective study

Lung cancer risk was investigated in relation to single nucleotide polymorphisms in genes involved in the inflammatory response. The aim was to see if polymorphisms modifying the inflammatory response are associated with risk of lung cancer and if there were interactions between the same polymorphism and factors, which modify an inflammatory response, such as smoking status, duration, and intensity, and use of NSAID. The functional SNPs IL-1B T-31C, IL6 G-174C, IL8 T-251A, IL10 C-592T, COX2 C8473T, COX2 A-1195G and PPARγ2 Pro 12Ala were included. A case-cohort study including 428 lung cancer cases and a sub-cohort of 800 persons was nested within a population-based prospective study of 57,053 individuals. Variant allele carriers of IL-1B T-31C were at increased risk of lung cancer (IRR = 1.51, 95% CI = 1.08–2.12). There was interaction between the polymorphism COX-2 T8473C and smoking status. Thus, non-smoking variant allele carriers were at 5.75-fold (95% CI = 1.25–26.43) higher risk of lung cancer than for homozygous wild type allele carriers. Lung cancer risk was similar for all genotype carriers among past and current smokers. There were, however, very few non-smoking lung cancer cases. There was interaction between IL-1B T-31C, COX-2 A-1195G and PPARγ2 Pro 12Ala and NSAID use in relation to lung cancer risk. For the two latter, NSAID use was only associated with a lower cancer risk among homozygous wild type allele carriers. p for interaction was 3 × 10 −6 for COX-2 A-1195G and 9 × 10 −5 for PPARγ2 Pro 12Ala. The results suggest that NSAID use may modify risk of lung cancer differently depending on the genotype.

Environmental tobacco smoke and lung cancer: a case-control study in Germany.

To assess the association between exposure to environmental tobacco smoke (ETS) and lung cancer, the authors personally interviewed 292 lifelong nonsmoking lung cancer cases (recruited from 15 hospitals in the study area) and 1,338 nonsmoking controls (randomly selected by population registries) between 1990 and 1996 in Germany. Subjects were asked by a standardized questionnaire about exposure to ETS in childhood, by spouse, at work, and in transportation and social settings. Several indicators of these different sources of exposure were investigated, using not or low exposed subjects as the reference category. The most informative quantification index was weighted duration of exposure (hours x level of smokiness). No effect of ETS exposure during childhood and no clear effect of spousal ETS were observed. However, for the highest category of exposure, clear effects of ETS at the workplace (odds ratio (OR) = 1.93; 95% confidence interval (CI): 1.04, 3.58), in vehicles (OR = 2.64; 95% CI: 1.30, 5.36), and from all sources combined (OR = 1.39; 95% CI: 0.96, 2.01) were found. Adjustment for occupational carcinogens, radon, and diet did not appreciably change the results. These findings suggest that exposures to high levels of ETS at the workplace and in other public indoor settings appear to be important risk factors for lung cancer risk in nonsmokers.

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.

A European validation study of smoking and environmental tobacco smoke exposure in nonsmoking lung cancer cases and controls.

The purpose of this study was to validate, in a case-control study, the reporting by lung cancer cases and controls of their own lifetime smoking habits and of the smoking habit of the spouse. In a multicenter (Sweden, Spain, Italy) case-control study of environmental tobacco smoke (ETS) and lung cancer, subjects were screened by repeated probing to exclude regular smokers of one cigarette/day or more for one year or more, and to quantify any occasional smoking. We then performed a short validation interview with next-of-kin in three centers. Only five of 408 index subjects who had never smoked regularly (1.7 percent) were reported by next-of-kin to be former regular smokers. These subjects had a cumulative lifetime consumption of cigarettes below 1.1 pack years. Among 351 subjects with quantitative smoking information from both sources who reported ever smoking 400 cigarettes or less (the definition of never-smoker used in the multicenter ETS study), nine subjects (2.6 percent) had smoked more than this amount occasionally according to next-of-kin. Misclassification was not higher for cases than controls. Relative risks for lung cancer associated with indicators of ETS exposure were not substantially altered by excluding the nine possibly misclassified subjects. The reports from 223 pairs of index subjects and next-of kin regarding the cumulative amount smoked by the spouse agreed quite well (Spearman's rank correlation 0.75 for reported smokers, 0.92 for all subjects). Only one index subject failed to report a spouse who had smoked regularly (99 percent sensitivity). Smoking status and exposure to spousal ETS as reported by lung cancer cases and controls agreed strongly with reports by next-of-kin. Overall, our results suggest that bias from smoker misclassification is likely to be insignificant, and they contribute to the evidence linking exposure to ETS with an increased risk of lung cancer.

Familial risk of lung cancer among nonsmokers and their relatives.

The role of family history of lung cancer in predicting lung cancer risk among nonsmokers and their relatives was evaluated in a population-based family study conducted in metropolitan Detroit. Lung cancer risk factor data were collected through telephone interviews with 257 nonsmoking lung cancer cases 40-84 years of age diagnosed between 1984 and 1987, their 2,252 relatives, 277 nonsmoking controls, and their 2,408 relatives. Lung cancer in a first-degree relative was associated with a 7.2-fold (95% confidence interval 1.3-39.7) increased risk of lung cancer among nonsmokers in the 40- to 59-year-old age group. This significant increased risk remained after adjustment for the smoking, occupational, and medical history of each family member (relative risk = 6.1, 95% confidence interval 1.1-33.4). Offspring of nonsmoking cases comprised another lung cancer high risk group (relative risk = 7.2, 95% confidence interval 0.5-103). A positive family history did not increase lung cancer risk among nonsmokers 60-84 years of age or their relatives. These findings suggest that susceptibility to lung cancer in families of nonsmoking cases may be evident only in a subset of relatives of early-onset nonsmoking cases.

Risk Factors for Lung Cancer Among Nonsmoking Illinois Residents

The purpose of this study was to examine possible risk factors for lung cancer among nonsmokers. The Illinois State Cancer Registry was used to identify all nonsmoking lung cancer cases diagnosed between 1985 and 1987. Subjects were classified as nonsmokers only if their medical record specifically stated that they had never smoked during their lifetime. These cases were compared with nonsmoking colon cancer cases. White male nonsmoking lung cancer cases were more likely to have worked in the construction industry than controls [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2–2.3] and to have worked in the bus service and urban transit industry (OR = 2.6, 95% CI = 1.0–6.9), in the trucking service industry (OR = 2.1, 95% CI = 1.3–3.6), and in blast furnaces, steelworks, and rolling and finishing mills (OR = 1.9, 95% Cl = 1.0–3.6). White female cases were more likely to have worked as registered nurses than were the controls (OR = 1.9, 95% Cl = 1.0–3.5). Negative associations between lung cancer and farming were found in both white males (OR = 0.6, 95% CI = 0.5–0.7) and white females (OR = 0.1, 95% CI = 0.01–0.6). Several other less plausible associations between employment and lung cancer were also found. To determine whether urban residence and associated air pollution increased the risk of lung cancer for nonsmokers, rates among nonsmokers in Cook County were compared with those in the remainder of Illinois. Cook County rates of nonsmoking lung cancer were elevated among white females and nonwhite females, but not among males. Residences of the white female and nonwhite female lung cancer cases were mapped to determine whether clustering within Chicago had occurred. The absence of observable clustering suggests that the excess of female lung cancer cases in Cook County is not attributable to pollution.

Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases.

In the latter part of a large hospital case-control study of the relationship of type of cigarette smoked to risk of various smoking-associated diseases, patients answered questions on the smoking habits of their first spouse and on the extent of passive smoke exposure at home, at work, during travel and during leisure. In an extension of this study an attempt was made to obtain smoking habit data directly from the spouses of all lifelong non-smoking lung cancer cases and of two lifelong non-smoking matched controls for each case. The attempt was made regardless of whether the patients had answered passive smoking questions in hospital or not. Amongst lifelong non-smokers, passive smoking was not associated with any significant increase in risk of lung cancer, chronic bronchitis, ischaemic heart disease or stroke in any analysis. Limitations of past studies on passive smoking are discussed and the need for further research underlined. From all the available evidence, it appears that any effect of passive smoke on risk of any of the major diseases that have been associated with active smoking is at most small, and may not exist at all.