Risk Of Lung Cancer In Patients Research Articles

Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study

BackgroundThe effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years.MethodsThis nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable.ResultsDuring a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01).ConclusionsIn patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Mechanism of lnRNA-ICL involved in lung cancer development in COPD patients through modulating microRNA-19-3p/NKRF/NF-κB axis

The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.

Polymorphisms in DNA Repair and Xenobiotic Biotransformation Enzyme Genes and Lung Cancer Risk in Coal Mine Workers.

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic detoxification and DNA repair capacity. The aim of this study was to investigate the association between GSTM1 (deletion), APEX1 (rs1130409), XPD (rs13181) and NBS1 (rs1805794) gene polymorphisms and LC risk in patients who worked in coal mines. Methods: The study included 639 residents of the coal region of Western Siberia (Kemerovo region, Russia): 395 underground miners and 244 healthy men who do not work in industrial enterprises. Genotyping was performed using real-time and allele-specific PCR. Results: The results show that polymorphisms of APEX1 (recessive model: ORadj = 1.87; CI 95%: 1.01–3.48) and XPD (log additive model: ORadj = 2.25; CI 95%: 1.59–3.19) genes were associated with increased LC risk. GSTM1 large deletion l was linked with decreased risk of LC formation (ORadj = 0.59, CI 95%: 0.36–0.98). The multifactor dimensionality reduction method for 3-loci model of gene–gene interactions showed that the GSTM1 (large deletion)—APEX1 (rs1130409)—XPD (rs13181) model was related with a risk of LC development. Conclusions: The results of this study highlight an association between gene polymorphism combinations and LC risks in coal mine workers.

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and fixed airflow obstruction. Patients with COPD have increased risk of lung cancer (LC), and the coexistence of both diseases is associated with poorer survival. However, the mechanisms predisposing patients with COPD to LC development and poor prognosis remain unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus. Twenty‐two data sets were included (n = 876). We identified 133 DEGs and 145 DEGs in patients with COPD and LC compared with healthy controls, respectively. There were 1544 DEGs in patients with LC and coexisting COPD compared with COPD, and these DEGs are mainly involved in the cell cycle, DNA replication, p53 signalling and insulin signalling. The biological processes primarily associated with these DEGs are oxidation reduction and apoptosis. SPP1 was the only overlapping DEG that was up‐regulated in patients with COPD and/or LC, and this was validated by qPCR in an independent cohort. The area under the curve value for SPP1 was 0.893 (0.822–0.963) for the prediction of LC in patients with COPD. High expression of SPP1 in patients with LC was associated with shorter survival time. Up‐regulation of SPP1 may be associated with increased risk of LC in patients with COPD and therefore may have potential as a therapeutic target for LC in patients with COPD.

Human Insulin Therapy Is Associated With an Increased Risk of Lung Cancer: A Population-Based Retrospective Cohort Study

Background: Whether human insulin may affect lung cancer risk requires investigation.Methods: All patients with a diagnosis of diabetes mellitus from 1996 to 2009 were enrolled from Taiwan's National Health Insurance. An entry date was set on January 1, 2004, and 1,007,617 patients with type 2 diabetes mellitus diagnosed before 2004 were followed up for new-onset lung cancer until December 31, 2009. Incidence rates of lung cancer for never-users, ever-users, and tertiles of three dose-response exposure parameters (i.e., time since starting insulin, cumulative dose, and cumulative duration) were calculated. Adjusted hazard ratios were estimated by Cox proportional hazards models. The joint effect of insulin and chronic obstructive pulmonary disease was also evaluated.Results: There were 156,720 ever-users and 850,897 never-users. The respective case numbers of incident lung cancer were 3,007 (1.92%) and 13,677 (1.61%), and the respective incidence rates were 424.45 and 313.60 per 100,000 person-years. The adjusted hazard ratio comparing ever-users vs. never-users was 1.545 (95% confidence interval: 1.478–1.614). The hazard ratios for the different subgroups of the three dose–response parameters all suggested a significantly higher risk of lung cancer associated with insulin use (P trend < 0.0001). Compared to patients without insulin use and without chronic obstructive pulmonary disease, insulin users who also had chronic obstructive pulmonary disease had the highest risk of lung cancer (adjusted hazard ratio: 1.891, 95% confidence interval: 1.767–2.024).Conclusions: This study suggests a significant association between human insulin use and lung cancer risk in patients with type 2 diabetes mellitus.

Common Variants rs3815188 and rs1043994 on Notch3 Gene Confer Susceptibility to Lung Cancer: A Hospital-Based Case-Control Study.

The Notch signaling pathway is a mechanism that plays a role in the determination of cell fate during cell development. Signals between neighbor cells are amplified through the Notch receptors. Notch activity is related to general growth stages such as organogenesis and morphogenesis and has effects on cell differentiation, cell proliferation, and apoptosis. Lung cancer associated with degradation of proteins which regulate cellular activities such as cell growth, differentiation, proliferation and apoptosis or the loss of function of proteins due to mutations in the genes which that express these proteins. We aimed to determine the frequency of the Notch3 rs3815188 (C381T) and rs1043994 (G684A) polymorphisms and to investigate whether this gene is associated with genetic predisposition of development of lung cancer. In this study, DNA samples were extracted from the venous blood sample of 200 subjects (100 lung cancer patients and 100 controls). Notch3 rs3815188 (C381T) and rs1043994 (G684A) polymorphisms were determined using the restriction fragment length polymorphism method. A statistically significant difference was found between the patient and control groups for Notch3 gene rs3815188 and rs1043994 polymorphisms when evaluated in terms of genotype (p = 0.002 and p < 0.001, respectively) and allele frequencies (p < 0.05). In conclusion, the rs3815188 variant and rs1043994 variant of the Notch3 gene is associated with lung cancer risk in patients of Turkish origin.

Metformin and lung cancer risk in patients with type 2 diabetes mellitus.

This study evaluated whether metformin might reduce lung cancer risk. The reimbursement database of the Taiwan's National Health Insurance was used. A sample of 15414 never users and 280159 ever users of metformin (original sample) and a 1:1 matched-pairs of ever and never users (n=15414 in each group, matched sample) were recruited from patients with newly diagnosed type 2 diabetes mellitus during 1999-2005. They were followed until December 31, 2011. Cox regression incorporated with the inverse probability of treatment weighting using propensity score was used to estimate hazard ratios. Results showed that the respective incidence of lung cancer in ever and never users was 173.36 and 292.65 per 100000 person-years in the original sample; and was 211.71 and 292.65, respectively, in the matched sample. The overall hazard ratios (95% confidence intervals) of 0.586 (0.509-0.674) in the original sample and 0.717 (0.584-0.881) in the matched sample suggested a significantly lower risk among metformin users. Hazard ratios comparing the first (<22.60 months), second (22.60-46.67 months) and third (>46.67 months) tertile of cumulative duration of metformin use to never users was 1.163 (1.005-1.348), 0.612 (0.526-0.711) and 0.176 (0.148-0.210), respectively, in the original sample; and was 1.465 (1.131-1.897), 0.758 (0.566-1.016) and 0.228 (1.460-0.357) in the respective tertile of the matched sample. Sensitivity analyses after excluding patients with certain risk factors of cancer and subgroup analyses supported a favorable effect of metformin. In conclusion, metformin use may reduce lung cancer risk in patients with type 2 diabetes mellitus.

Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study.

PurposeChronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.ResultsAfter adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).MATERIALS AND METHODSThe study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose–response relationship, we categorized statin use into four groups in each cohort: < 28, 28–90, 91–365, and > 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users.ConclusionsStatins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma.

PurposeTo evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma.MethodsThe study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users.ResultsA total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively.ConclusionsPost-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

Lung cancer screening in patients with chronic obstructive pulmonary disease.

Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment.

Close Surveillance with Long-Term Follow-up of Subjects with Preinvasive Endobronchial Lesions.

Autofluorescence bronchoscopy (AFB) and computed tomography (CT) enable lung cancer (LC) detection at the early (pre-)invasive stage. However, LC risk in patients with preinvasive endobronchial lesions is unclear. To assess LC incidence and identify potential risk determinants in patients with preinvasive lesions. In our tertiary care referral center, 164 subjects with preinvasive lesions were monitored up to 12.5 years by repeated AFB and CT. Occurrence of LC was monitored. Clinical management depended on histological grade, with cancer patients receiving standard care. Potential risk determinants (smoking status, baseline histology, cancer history, and chronic obstructive pulmonary disease [COPD] status) were evaluated in relation to cancer occurrence, event-free survival (EFS), and overall survival (OS). During surveillance (median of 30 mo, range 4-152) of 164 subjects with preinvasive lesions (80 high grade and 84 low grade at inclusion), 61 LCs were detected in 55 subjects (median time to event 16.5 mo). Twenty-three LCs (38%) were detected by CT, and 38 (62%) were detected by AFB. More cancers (36 of 61; 59%) developed from separate, rather than initial lesional sites. Subjects with high-grade lesions were more likely to be diagnosed with LC at the same or another site in the lungs than those with low-grade lesions (P = 0.03). Independent risk determinants for OS were previous curatively treated cancer and COPD (P ≤ 0.05). Presence of preinvasive lesions, especially high-grade lesions, may serve as LC risk markers. LCs occur both at preinvasive lesion sites and elsewhere in the bronchial epithelium or lung parenchyma. Prospective validation of biomarkers and randomized intervention studies are needed to determine optimal management strategies.

Metformin use and lung cancer risk in patients with diabetes.

Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages ≥40 years, who completed a health-related survey administered between 1994 and 1996, data on prescribed diabetes medications were obtained from electronic pharmacy records. Follow-up for incident lung cancer occurred from January 1, 1997, until June 30, 2012. Using Cox regression, we estimated lung cancer risk associated with new use of metformin, along with total duration, recency, and cumulative dose (all modeled as time-dependent covariates), adjusting for potential confounding factors. During 428,557 person-years of follow-up, 747 patients were diagnosed with lung cancer. No association was found with duration, dose, or recency of metformin use and overall lung cancer risk. Among never smokers, however, ever use was inversely associated with lung cancer risk [HR, 0.57; 95% confidence interval (CI), 0.33-0.99], and risk appeared to decrease monotonically with longer use (≥5 years: HR, 0.48; 95% CI, 0.21-1.09). Among current smokers, corresponding risk estimates were >1.0, although not statistically significant. Consistent with this variation in effect by smoking history, longer use was suggestively associated with lower adenocarcinoma risk (HR, 0.69; 95% CI, 0.40-1.17), but higher small cell carcinoma risk (HR, 1.82; 95% CI, 0.85-3.91). In this population, we found no evidence that metformin use affects overall lung cancer risk. The observed variation in association by smoking history and histology requires further confirmation.

The cyclooxygenase-2/thromboxane A2 pathway: a bridge from rheumatoid arthritis to lung cancer?

Patients with rheumatoid arthritis (RA) appear to be at a higher risk of lung cancer (LC). Although the connection between RA and LC has been an active area of research for many years, the molecular pathogenesis of the disease process remains unclear. The cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway has been shown to play a potential role in LC development through an auto-regulatory feedback loop. An increased level of TxA2 has been found in RA patients, and intriguingly, the positive feedback loop for the COX-2/TxA2 pathway was shown to have a potential function in RA fibroblast-like synoviocytes (RA-FLS). Thus, the molecular basis of LC development in patients with RA has been at least in partly described. It is possible that COX-2-derived TxA2 could be monitored for the early detection of LC in RA patients, and targeting this molecular pathway may decrease the risk of LC in patients with RA.

Conventional hypoglycaemic agents and the risk of lung cancer in patients with diabetes: a meta-analysis.

BackgroundAccumulating evidence suggests that hypoglycaemic agents influence lung cancer risk in patients with diabetes. It remains to be fully elucidated whether conventional hypoglycaemic agents (metformin, sulfonylureas, thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients with diabetes.MethodsWe performed a meta-analysis using EMBASE, MEDLINE and Web of Science to search randomised controlled trials (RCTs), cohort studies, and case-control studies published up to October 2013 that assessed the effects of metformin, sulfonylurea, TZDs or insulin on lung cancer risk in subjects with diabetes. Fixed and random effects meta-analysis models were used, and the effect size was expressed as a summary odds ratio (OR) with 95% confidence intervals (CI). The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was applied to define the quality of the evidence.ResultsAnalysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06). Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02). Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35). However, all data from RCTs failed to demonstrate a statistically significant effect.ConclusionsThis analysis demonstrated that metformin use may reduce lung cancer risk in patients with diabetes but not in a smoking-adjusted subgroup and that insulin use may be associated with an increased lung cancer risk in subjects with diabetes.

Testing of human papillomavirus in lung cancer and non-tumor lung tissue

BackgroundRisk factors for lung cancer, such as cigarette smoking, environmental pollution, asbestos, and genetic determinants, are well-known, whereas involvement of the human papillomavirus (HPV) is still unclear.MethodsWe examined a series of 100 lung cancer patients from Italy and the UK for the presence of HPV DNA in both lung tumor specimens and adjacent non-tumoral specimens from the same patients. Thirty-five of the most clinically relevant HPV types were assayed using PCR amplification of the highly conserved L1 region of the viral genome followed by hybridization with specific probes.ResultsNo HPV was detected in tumor specimens nor in normal lung tissue of any patient.ConclusionsThese data indicate that, in this Western series, HPV is not associated with the risk of lung cancer. Our findings will help refine estimates of lung cancer risk in patients affected by a common viral infection involved in other types of human cancer.

Existing General Population Models Inaccurately Predict Lung Cancer Risk in Patients Referred for Surgical Evaluation

Patients undergoing resections for suspicious pulmonary lesions have a 9% to 55% benign rate. Validated prediction models exist to estimate the probability of malignancy in a general population and current practice guidelines recommend their use. We evaluated these models in a surgical population to determine the accuracy of existing models to predict benign or malignant disease. We conducted a retrospective review of our thoracic surgery quality improvement database (2005 to 2008) to identify patients who underwent resection of a pulmonary lesion. Patients were stratified into subgroups based on age, smoking status, and fluorodeoxyglucose positron emission tomography (PET) results. The probability of malignancy was calculated for each patient using the Mayo and solitary pulmonary nodules prediction models. Receiver operating characteristic and calibration curves were used to measure model performance. A total of 189 patients met selection criteria; 73% were malignant. Patients with preoperative PET scans were divided into four subgroups based on age, smoking history, and nodule PET avidity. Older smokers with PET-avid lesions had a 90% malignancy rate. Patients with PET-nonavid lesions, PET-avid lesions with age less than 50 years, or never smokers of any age had a 62% malignancy rate. The area under the receiver operating characteristic curve for the Mayo and solitary pulmonary nodules models was 0.79 and 0.80, respectively; however, the models were poorly calibrated (p<0.001). Despite improvements in diagnostic and imaging techniques, current general population models do not accurately predict lung cancer among patients referred for surgical evaluation. Prediction models with greater accuracy are needed to identify patients with benign disease to reduce nontherapeutic resections.

Peroxisome Proliferator-Activated Receptor-γ in Lung Cancer: Defining Specific Versus “Off-Target― Effectors

A large number of studies have indicated that thiazolidinediones (TZDs) such as rosiglitazone and pioglitazone inhibit tumor growth, progression, and metastasis. These agents are specific agonists for the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) but also engage other pathways. In lung cancer, these agents have been shown to induce apoptosis and inhibit tumor growth in xenograft models. Retrospective studies have indicated a significant decrease in lung cancer risk in patients using these agents, suggesting that TZDs may be chemopreventive for lung cancer. However, emerging data suggest that chronic use of these agents is associated with increased risk of adverse cardiovascular events. It is therefore critical to determine the relative contributions of PPARγ-dependent versus PPARγ-independent pathways in mediating both the anti-tumorigenic effects and the cardiovascular effects of TZDs. This review examines these pathways with a specific focus on the role of TZDs and PPARγ in lung cancer.

GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk

Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In this study we investigated GSTM1, GSTT1 and GSTP1 status in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. Cases were all patients ( n=94) currently with, or with a history of, tumours of the lung, trachea or bronchus. The control group were all other patients ( n=165) who were free of benign and malignant tumours both at the time of, or prior to, diagnosis. All patients were interviewed for information on lifestyle risk factors, and DNA extracted from bronchial lavage and blood samples was used for genotyping. GSTM1 null genotype was associated with decreased lung cancer risk (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.29–0.87), particularly among men (OR 0.43, 95% CI 0.21–0.87) and those above the median age (OR 0.33, 95% CI 0.15–0.70). No difference in GSTT1 and GSTP1 genotype distribution was seen between cases and controls. The GSTM1 null genotype was associated with a decreased risk of squamous cell carcinoma: the OR, adjusted for age, sex and pack years was 0.32 (95% CI 0.12–0.82). As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.

Polymorphisms in the NAD( P) H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population

NAD(P)H: quinone oxidoreductase (NQO1) protects the cell against cytotoxicity by reducing the concentration of free quinone available for single electron reduction. The NQO1 gene is polymorphic and the variant protein exhibits just 2% of the enzymatic activity of the wildtype protein. In this study, we investigated NQO1 genotype in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. The cases were patients with a current, or history of, malignant tumour of the lung, trachea or bronchus. The control group were all other patients attending the clinic who had never been diagnosed with a tumour. DNA extraction from bronchial lavage or blood samples and genotyping was successfully carried out for 82 of the cases and 145 controls. Patients carrying at least one variant allele were found to have almost a 4-fold increased risk of developing small cell lung cancer (adjusted OR=3.80, 95% C.I. 1.19–12.1). No association between NQO1 genotypes and non-small cell lung cancer risk was found. Furthermore, the excess small cell lung cancer risk associated with non-wildtype NQO1 genotypes was only apparent in heavy smokers where there was a >10-fold increased risk (adjusted OR=12.5, 95% C.I. 2.1–75.5). These results suggest that the NQO1 protein may be involved in the detoxification of those carcinogens associated with the development of small cell lung cancer. Individuals with reduced enzyme activity, due to a polymorphism in this gene, may therefore have an increased risk of developing this disease.