Subsequent Risk Of Lung Cancer Research Articles

Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases.

The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR=1.61, 95% CI: 1.48-1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5years, ≥5years, ≥10years, ≥20years, and ≥30years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR=1.25, P <0.001), endometrial (SIR=1.40, P =0.019), cervical (SIR=2.56, P <0.001), and ovarian cancer (SIR=1.50, P =0.010). FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/.

Hospital-Treated Infectious Diseases, Infection Burden, and Risk of Lung Cancer: An Observational and Mendelian Randomization Study

BackgroundAlthough infections play a role in the development of lung cancer, the longitudinal association between infection and the risk of lung cancer is disputed and data relating to pathogen types and infection sites is sparse.Research Question:How do infections impact subsequent lung cancer risk and whether the impact is limited to specific microbes rather than infection burden? MethodsWe ascertained 900+ infectious diseases from the UK Biobank study. Short- and long-term effect of infections was assessed using time-varying Cox proportional hazard models. The analysis was repeated, excluding patients with concurrent multi-pathogen infections or outcomes within the ten years after initial hospitalization for the index infection. Life table was used to estimate years of life lost from lung cancer. Infection burden was defined as the sum of the number of infection episodes over time and co-occurring infections. The genome-wide association studies (GWAS) used in two-sample Mendelian randomization (MR) were obtained from mostly European ancestry. ResultsHospital-treated infectious disease was associated with a greater risk of lung cancer (adjusted HR [aHR] 1.79 [95% CI 1.74–1.83]). aHRs for lung cancer ranged from 1.39 to 2.82 across pathogen types. The impact of lower respiratory tract infections (LRTIs) on lung cancer was the strongest, with an aHR of 3.22 [95% CI 2.64–3.92], while the aHR for extra-LRTIs was 1.29 [1.16–1.44]). A dose-response association was observed between infection burden and lung cancer risk across different FEV1% predicted (p-trend <0.001). Multiple infections led to a significant life lost from lung cancer at the age of 50. MR analysis reaffirmed the causal association. InterpretationBoth observational and genetic analyses suggested that infectious diseases could increase the risk of lung cancer. The dual perspective on the LRTIs and extra-LRTIs impacts may inform lung cancer preventive strategies.

The Impact of Malnutrition on the Developing Lung and Long-Term Lung Health: A Narrative Review of Global Literature.

Worldwide, over 2 billion children under the age of 5 experience stunting, wasting, or are underweight. Malnutrition contributes to 45% of all deaths in this age group (approximately 3.1 million deaths) [1]. Poverty, food insecurity, suboptimal feeding practices, climate change, and conflict are all contributing factors. Malnutrition causes significant respiratory problems, including increased risk of respiratory infections, impaired lung function, and increased risk of subsequent adult respiratory disease, including asthma, COPD, and lung cancer. Childhood malnutrition not only has serious consequences for children's health but it also has numerous consequences on wellbeing and educational attainment. Childhood malnutrition is a complex and multifaceted problem. However, by understanding and addressing the underlying causes, and investing in prevention and treatment programs, it is possible to maximize children's health and wellbeing on a global scale. This narrative review will focus on the impact of childhood malnutrition on lung development, the consequent respiratory disease, and what actions can be taken to reduce the burden of malnutrition on lung health.

Abstract LB151: Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States

Abstract Background Breast cancer survivors face an elevated risk of subsequent primary lung cancer (SPLC), especially those who received radiotherapy. Nevertheless, the association of radiotherapy for breast cancer and the risk of subtype-specific lung cancer is unknown. Methods Females diagnosed with first primary breast cancer at ages 20-84 years from 1992-2020 were identified from 12 Surveillance, Epidemiology, and End Results registries. Follow-up began at 2 months from breast cancer diagnosis and ended at subsequent lung cancer diagnosis, last known vital status, death, or December 31, 2020. Standardized incidence ratios (SIRs) and excess absolute risks (EARs, per 10,000 women) were calculated for each histological subtype of lung cancer (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, and others) using expected rates of each subtype in the SEER population. Subgroup analyses were conducted by treatment for breast cancer (radiotherapy yes or no/unknown), overall and stratified by the relative position (ipsilateral and contralateral) of the breast and SPLC. Results Of all 550,007 breast cancer survivors (&amp;gt;50 years old, 74%; non-Hispanic Whites, 67%; localized, 51%), 8,014 SPLCs were diagnosed during a mean follow-up of 9.7 years. 52.6% of the participants received radiotherapy treatment. Compared with the general population, breast cancer survivors had a statistically significantly higher risk of lung cancer with subtype-specific SIR being greatest for adenocarcinoma (Observed N=4337; SIR=1.20, 95% Confidence Interval [CI]=1.16-1.24; EAR=1.35), followed by squamous cell carcinoma (Observed N=1368; SIR=1.11, 95% CI=1.05-1.17; EAR=0.26) and small cell carcinoma (Observed N=1026; SIR=1.08, 95% CI=1.02-1.15; EAR=0.14). When stratified by radiotherapy receipt, the increased risk associated with adenocarcinoma did not vary across strata. In contrast, the increased risk for squamous and transitional cell carcinoma and small cell carcinoma were confined to those who received radiotherapy (SIR=1.16, 95% CI=1.08-1.24 vs SIR=1.06, 95% CI=0.98-1.15 for squamous and transitional cell carcinoma; SIR=1.15, 95% CI=1.06-1.25 vs SIR= 1.00, 95% CI=0.91-1.09 for small cell carcinoma). Further analysis by laterality showed that associations of treatment receipt with increased risk of lung cancer were confined to ipsilateral SPLC for these two subtypes. Conclusion Different subtypes of lung cancer may have distinct associations with prior radiation treatment in individuals who have survived breast cancer. The findings have implications for evaluating risks and implementing surveillance for subsequent primary lung cancer in the growing population of breast cancer survivors. Citation Format: Chenxi Jiang, Rachel A. Freedman, Ahmedin Jemal, Hyuna Sung. Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB151.

MA03.08 Regular Use of Pharmaceutical Opioids and Subsequent Risk of Lung Cancer

MA03.08 Regular Use of Pharmaceutical Opioids and Subsequent Risk of Lung Cancer

Accelerated subsequent lung cancer after post-operative radiotherapy for breast cancer

BackgroundPost-operative whole breast radiotherapy for breast cancer (BC) may increase the risk of subsequent lung cancer (LC). The impact of radiotherapy intensification (boost) has not been specifically explored in this context. We investigated the role of radiation modalities on the development of subsequent LC among our patients treated by radiotherapy for localized BC. MethodsAll patients with a diagnosis of LC between 2000 and 2020 with a history of prior localized BC treated by surgery and post-operative radiotherapy were retrospectively reviewed. Primary endpoint was time to first diagnosis of LC after BC treatment with radiotherapy (RT). ResultsFrom 98 patients who developed subsequent LC after primary BC treated with post-operative RT, 38% of patients (n = 37) received an additional RT boost, and 46% (n = 45) received hormonal treatment post radiation. A total of 61% (n = 60) were smokers. With regards to LC characteristics, adenocarcinoma was the most frequent histology (68%, n = 66); 36% (n = 35) harbored at least 1 molecular alteration, 57% (n = 20) of them being amenable to targeted therapy. Median time to first diagnosis of LC was 6 years [1.7–28.4 yrs] in the whole cohort. In the subgroup of patients treated with boost this time was reduced to 4 years [1.8–20.8 years] compared to 8 years for patients without boost [1.7–28.4 yrs] (p = 0.007). Boost, smoking usage, endocrine therapy, and age <50 yrs old at BC radiation remained independent factors associated with shorter time to first diagnosis of LC after BC treatment. DiscussionWe report for the first time the potential impact of boost -part of BC radiation treatment- for BC on the risk of subsequent LC. The impact of low dose radiation on lung parenchyma could explain this phenomenon, but the underlying physiopathology is still under investigation. This work highlights the need for clinicians to identify patients at risk of developing faster subsequent thoracic malignancy after BC radiation, for implementing personalized surveillance.

Clonal Hematopoiesis and Risk of Incident Lung Cancer.

To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer. Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood draw, sex, race, and smoking status. A similar nested case-control study (141 cases/652 controls) was conducted among 27,975 participants with whole-exome sequencing in the Mass General Brigham Biobank (MGBB, 2010-2021). In parallel, we compared CH frequency in published data from 5,003 patients with solid tumor (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. In UKBB, the presence of CH was associated with increased risk of lung cancer (cases: 12.5% v controls: 8.7%; multivariable-adjusted odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74). The association remained robust after excluding participants with chronic obstructive pulmonary disease. No significant interactions with known risk factors, including polygenic risk score and C-reactive protein, were identified. In MGBB, we observed similar enrichment of CH in lung cancer (cases: 15.6% v controls: 12.7%). The meta-analyzed OR (95% CI) of UKBB and MGBB was 1.35 (1.08 to 1.68) for CH overall and 1.61 (1.19 to 2.18) for variant allele frequencies ≥ 10%. In Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, CH with a variant allele frequency ≥ 10% was enriched in pretreatment lung cancer compared with other tumors after adjusting for age, sex, and smoking (OR for lung v breast cancer: 1.61; 95% CI, 1.03 to 2.53). Independent of known risk factors, CH is associated with increased risk of lung cancer.

Pre-diagnostic circulating p53 autoantibodies and subsequent lung cancer risk in low-income African and European Americans

IntroductionMutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking. MethodsIn this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies. ResultsAfter adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10–8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24–6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30–16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33–13.89). ConclusionOur findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.

Early natural menopause is associated with poor lung health and increased mortality among female smokers

Early natural menopause has been regarded as a biomarker of reproductive and somatic aging. Cigarette smoking is the most harmful factor for lung health and also an established risk factor for early menopause. Understanding the effect of early menopause on health outcomes in middle-aged and older female smokers is important to develop preventive strategies. This study aimed to examine the associations of early menopause with multiple lung health and aging biomarkers, lung cancer risk, and all-cause and cause-specific mortality in postmenopausal women who were moderate or heavy smokers. This study was conducted on postmenopausal women with natural (n=1038) or surgical (n=628) menopause from the Pittsburgh Lung Screening Study. The Pittsburgh Lung Screening Study is a community-based research cohort of current and former smokers, screened with low-dose computed tomography and followed up for lung cancer. Early menopause was defined as occurring before 45 years of age. The analyses were stratified by menopause types because of the different biological and medical causes of natural and surgical menopause. Statistical methods included linear model, generalized linear model, linear mixed-effects model, and time-to-event analysis. The average age of the 1666 female smokers was 59.4±6.7 years, with 1519 (91.2%) of the population as non-Hispanic Whites and 1064 (63.9%) of the population as current smokers at baseline. Overall, 646 (39%) women reported early menopause, including 198 (19.1%) women with natural menopause and 448 (71.3%) women with surgical menopause (P<.001). Demographic variables did not differ between early and nonearly menopause groups, regardless of menopause type. Significant associations were identified between early natural menopause and higher risk of wheezing (odds ratio, 1.65; P<.01), chronic bronchitis (odds ratio, 1.73; P<.01), and radiographic emphysema (odds ratio, 1.70; P<.001) and lower baseline lung spirometry in an obstructive pattern (-104.8 mL/s for forced expiratory volume in the first second with P<.01,-78.6 mL for forced vital capacity with P=.04, and-2.1% for forced expiratory volume in the first second-to-forced vital capacity ratio with P=.01). In addition, early natural menopause was associated with a more rapid decline of forced expiratory volume in the first second-to-forced vital capacity ratio (-0.16% per year; P=.01) and incident airway obstruction (odds ratio, 2.02; P=.04). Furthermore, women early natural menopause had a 40% increased risk of death (P=.023), which was mainly driven by respiratory diseases (hazard ratio, 2.32; P<.001). Mediation analyses further identified that more than 33.3% of the magnitude of the associations between early natural menopause and all-cause and respiratory mortality were explained by baseline forced expiratory volume in the first second. Additional analyses in women with natural menopause identified that the associations between continuous smoking and subsequent lung cancer risk and cancer mortality were moderated by early menopause status, and females with early natural menopause who continued smoking had the worst outcomes (hazard ratio, >4.6; P<.001). This study did not find associations reported above in female smokers with surgical menopause. Early natural menopause was found to be a risk factor for malignant and nonmalignant lung diseases and mortality in middle-aged and older female smokers. These findings have strong public health relevance as preventive strategies, including smoking cessation and chest computed tomography screening, should target this population (ie, female smokers with early natural menopause) to improve their postmenopausal health and well-being.

Endogenous sex hormones, aromatase activity and lung cancer risk in postmenopausal never-smoking women.

Although reproductive factors have been repeatedly associated with lung cancer risk, no study to date has directly evaluated the relationship with endogenous sex hormones nor with aromatase activity in postmenopausal never-smoking women. A case-control study of 397 incident lung cancer cases and their individually matched controls, nested within the Shanghai Women's Health Study, was conducted among postmenopausal women who were lifetime never smokers. Prediagnostic concentrations of sex hormones was quantitated using LC-MS/MS assays in plasma. The product-substrate molar ratio of estrone to androstenedione was used as an index of aromatase activity (IAA). Multivariable conditional logistic regression models were used to calculate odds ratios (ORs) for lung cancer. Baseline concentrations of estradiol, free testosterone and IAA were inversely associated with subsequent risk of lung cancer in multivariable-adjusted models. When further adjusted for body mass index, the inverse association with estradiol was attenuated and no longer statistically significant, but the association with free testosterone and IAA remained. In analyses confined to participants having never used menopausal hormone therapy in 376 case-control pairs, the inverse association with free testosterone and IAA was slightly strengthened. OR for the highest vs the lowest quartile of free testosterone was 0.55 (95% CI=0.34-0.90; Ptrend =.03), and the corresponding OR for IAA was 0.57 (95% CI=0.34-0.96; Ptrend =.04). Our study, for the first time, suggests that higher levels of circulating free testosterone and estimated aromatase activity may be associated with lower lung cancer risk in postmenopausal never-smoking women.

Risk and Influencing Factors for Subsequent Primary Lung Cancer After Treatment of Breast Cancer: A Systematic Review and Two Meta-Analyses Based on Four Million Cases

IntroductionTo compare the risk of developing lung cancer between patients with breast cancer and the general population and explore the risk factors for the development of primary lung cancer after treatment for breast cancer. MethodsThe PubMed, EMBASE, and Web of Science databases were searched from the establishment date to October 11, 2020. Two separate meta-analyses were performed: one focused on studies reporting the risk of subsequent lung cancer after breast cancer and one focused on studies exploring the risk factors for subsequent lung cancer in patients with breast cancer. The standardized incidence ratios with 95% confidence intervals were combined to compare the risk of developing lung cancer between patients with breast cancer and the general population. The relative risks (RRs) or ORs with 95% confidence intervals were combined to assess the association of clinicopathological parameters with the risk of developing lung cancer after breast cancer. All statistical analyses were conducted by STATA 12.0. ResultsA total of 15 studies involving 1,161,979 patients were eventually included in the first meta-analysis, and the pooled results indicated that female patients with breast cancer revealed a significantly higher risk of developing subsequent lung cancer (standardized incidence ratio = 1.25, p < 0.001). In addition, a total of 22 articles involving 3,090,620 patients were included in the second meta-analysis. The pooled results indicated that smoking (OR = 9.73, p < 0.001) and radiotherapy (RR = 1.40, p < 0.001) were risk factors for developing subsequent lung cancer in patients with breast cancer, and chemotherapy (RR = 0.69, p = 0.002), positive estrogen receptor status (RR = 0.93, p = 0.014) and positive progesterone receptor status (RR = 0.86, p < 0.001) were protective factors. Meanwhile, subgroup analysis based on the relative position of the breast and lung cancers (ipsilateral versus contralateral) was conducted, which indicated that radiotherapy only increased the risk of ipsilateral lung cancer in patients with breast cancer (RR = 1.27, p = 0.001). ConclusionsPatients with breast cancer are more likely to develop lung cancer than the general population, and the risk of developing primary lung cancer after breast cancer is affected by smoking, radiotherapy, chemotherapy, estrogen receptor status and progesterone receptor status.

Body Mass Index, Height, Weight Change, and Subsequent Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

Body mass index (BMI) is inversely associated with lung cancer risk, while residual confounding by smoking or weight change is controversial. Evidence on height and lung cancer is scarce. We investigated the associations between anthropometrics, BMI, and height, and incidence of lung cancer among 92,098 study subjects (44,158 men and 47,940 women) in the Japan Public Health Center-based Prospective Study. Cox proportional hazards regression was performed with adjustment for potential confounders and by cancer subtypes and smoking status. Information on weight and height was self-reported at baseline, and validated using measured health check-up data. During follow-up between 1990 and 2013 (average, 19.1 years), a total of 2,152 lung cancer cases were newly diagnosed. In a multivariate regression model, lower BMI was positively associated with overall lung cancer risk [<19 kg/m2 HR = 1.48; 95% confidence interval (CI) = 1.18-1.85 and 19-22.9 kg/m2; HR = 1.19; 95% CI = 1.05-1.35; P trend = <0.001] in men. The risk estimate was also elevated for adenocarcinoma in the BMI <19 kg/m2 category and for squamous cell carcinoma among men in the 19-22.9 kg/m2 BMI category. An association was also observed between low BMI, weight decrease, and squamous cell carcinoma in women. No significant associations were observed for other weight categories, height, weight change and lung cancer, adenocarcinoma, squamous and small cell carcinoma. Our prospective study suggests that lower BMI may be associated with an increased risk of smoking-related lung cancer in Japan, irrespective of gender. This study highlights the association between lower BMI and the risk of lung cancer in men.

Increased risk of secondary lung cancer in patients with tuberculosis: A nationwide, population-based cohort study.

BackgroundTuberculosis (TB) presents a global threat in the world and the lung is the frequent site of metastatic focus. A previous study demonstrated that TB might increase primary lung cancer risk by two-fold for more than 20 years after the TB diagnosis. However, no large-scale study has evaluated the risk of TB and secondary lung cancer. Thus, we evaluated the risk of secondary lung cancer in patients with or without tuberculosis (TB) using a nationwide population-based dataset.MethodsIn a cohort study of 1,936,512 individuals, we selected 6934 patients among patients with primary cancer and TB infection, based on the International Classification of Disease (ICD-p-CM) codes 010–011 from 2000 to 2015. The control cohort comprised 13,868 randomly selected, propensity-matched patients (by age, gender, and index date) without TB exposure. Using this adjusted date, a possible association between TB and the risk of developing secondary lung cancer was estimated using a Cox proportional hazards regression model.ResultsDuring the follow-up period, secondary lung cancer was diagnosed in 761 (10.97%) patients with TB and 1263 (9.11%) patients without TB. After adjusting for covariates, the risk of secondary lung cancer was 1.67 times greater among primary cancer in the cohort with TB than in the cohort without TB. Stratification revealed that every comorbidity (including diabetes, hypertension, cirrhosis, congestive heart failure, cardiovascular accident, chronic kidney disease, chronic obstructive pulmonary disease) significantly increased the risk of secondary lung cancer when comparing the TB cohort with the non-TB cohort. Moreover, the primary cancer types (including head and neck, colorectal cancer, soft tissue sarcoma, breast, kidney, and thyroid cancer) had a more significant risk of becoming secondary lung cancer.ConclusionA significant association exists between TB and the subsequent risk for metastasis among primary cancers and comorbidities. Therefore, TB patients should be evaluated for the subsequent risk of secondary lung cancer.

Incidence of lung cancer following pneumonia in smokers: a population-based study.

Pneumonia is more common in smokers compared with non-smokers. A high 1-year prevalence of lung cancer following hospitalization for pneumonia was demonstrated in heavy smokers. To assess the association between hospitalization for pneumonia among ever-smokers and subsequent lung cancer risk. Retrospective analysis. The study cohort included all ever-smokers aged 55-80 hospitalized for pneumonia between the years 2010-15 covered by a large medical insurer in Israel. Controls were matched to cases by age in a 4:1 ratio. The primary outcome was the association between hospitalization for pneumonia and subsequent 1-year incidence of lung cancer, adjusted for gender, smoking status (past/current) and pack years. Pre-specified sensitivity analyses excluded heavy smokers (smoking history of more than 30 pack years) and patients diagnosed with lung cancer within 30 days of hospitalization, as they probably had clinical or radiological findings suggestive of lung cancer, making them ineligible for screening. Lung cancer was identified in 275 of 12 807 (2.1%) patients following hospitalization for pneumonia and in 44 of 51 228 (0.1%) controls (adjusted odds ratio 22.46, 95% CI 16.29-30.96, P < 0.001). Among patients hospitalized for pneumonia, 1-year lung cancer incidence remained high after excluding heavy smokers and patients diagnosed within 30 days of the index date (1.3% and 1.4%, respectively). Hospitalization for pneumonia is associated with high 1-year incidence of lung cancer in ever-smokers, supporting the important role of the widely used practice of performing follow up imaging post-pneumonia to exclude occult malignancy.

Long-term cancer risk associated with lung nodules observed on low-dose screening CT scans

ObjectiveNon-calcified nodules (NCNs) associated with false positive low-dose CT (LDCT) lung cancer screens have been attributed to various causes. Some, however, may represent lung cancer precursors. An association of NCNs with long-term lung cancer risk would provide indirect evidence of some NCNs being cancer precursors. MethodsLDCT arm participants in the National Lung Screening Trial (NLST) received LDCT screens at baseline and years 1-2. The relationship between NCNs found on LDCT screens and subsequent lung cancer diagnosis over different time periods was examined at the person and lobe level. For the latter, a lobe had a cancer outcome only if the cancer was located in the lobe. Separate analyses were performed on baseline and post-baseline LDCT findings; for the latter, those with baseline NCNs were excluded and only new (non-pre-existing) NCNs examined. Raw and adjusted rate-ratios (RRs) were computed for presence of NCNs and subsequent lung cancer risk; adjusted RRs controlled for demographic and smoking factors. Results26,309 participants received the baseline LDCT screen. Over median 11.3 years follow-up, 1675 lung cancers were diagnosed. Adjusted RRs for time periods 0–4, 4–8 and 8−12 years following the baseline screen were 5.1 (95 % CI:4.4–5.9), 1.5 (95 % CI:1.3–1.9) and 1.5 (95 % CI:1.2-1.8) at the person-level and 14.7 (95 % CI:12.6–17.2), 2.6 (95 % CI: 2.0–3.4) and 2.2 (95 % CI:1.6–2.9) at the lobe-level. 18,585 participants were included in the post-baseline analysis. Adjusted RRs for periods 0–4, 4–8 and 8−11 years were 5.6 (95 % CI: 4.5–7.0), 1.9 (95 % CI: 1.3–2.7) and 1.6 (95 % CI: 0.9–2.9) at the person-level and 19.6 (95 % CI:14.9–25.3), 2.5 (95 % CI:1.3–4.7) and 3.3 (95 % CI:1.4–7.6) at the lobe-level. Raw RRs were similar. ConclusionNCNs are associated with excess long-term lung cancer risk, suggesting that some may be lung cancer precursors.

Quantitative Imaging Markers of Lung Function in a Smoking Population Distinguish COPD Subgroups with Differential Lung Cancer Risk.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with respect to onset, progression, and response to therapy. Incorporating clinical- and imaging-based features to refine COPD phenotypes provides valuable information beyond that obtained from traditional clinical evaluations. We characterized the spectrum of COPD-related phenotypes in a sample of former and current smokers and evaluated how these subgroups differ with respect to sociodemographic characteristics, COPD-related comorbidities, and subsequent risk of lung cancer. White (N = 659) and African American (N = 520) male and female participants without lung cancer (controls) in the INHALE study who completed a chest CT scan, interview, and spirometry test were used to define distinct COPD-related subgroups based on hierarchical clustering. Seven variables were used to define clusters: pack years, quit years, FEV1/FVC, % predicted FEV1, and from quantitative CT (qCT) imaging, % emphysema, % air trapping, and mean lung density ratio. Cluster definitions were then applied to INHALE lung cancer cases (N = 576) to evaluate lung cancer risk. Five clusters were identified that differed significantly with respect to sociodemographic (e.g., race, age) and clinical (e.g., BMI, limitations due to breathing difficulties) characteristics. Increased risk of lung cancer was associated with increasingly detrimental lung function clusters (when ordered from most detrimental to least detrimental). Measures of lung function vary considerably among smokers and are not fully explained by smoking intensity. Combining clinical (spirometry) and radiologic (qCT) measures of COPD defines a spectrum of lung disease that predicts lung cancer risk differentially among patient clusters.

Dietary consumption of antioxidant vitamins and subsequent lung cancer risk: The Japan Public Health Center-based prospective study.

While many epidemiological studies have studied the association between lung cancer risk and fruits and vegetable consumption (the major sources of antioxidant vitamins), only a few have investigated the direct association with antioxidants in consideration of cancer subtypes and smoking status. Here, we examined the association between consumption of antioxidant vitamins and lung cancer risk in one of the largest prospective cohort studies in Japan. We investigated the association of dietary antioxidant vitamins intake, namely retinol, vitamin C, vitamin E, α-carotene, and β-carotene and subsequent incidence of lung cancer among 38,207 men and 41,498 women in the Japan Public Health Center-based prospective study. Cox proportional hazard regression was performed with adjustment for potential confounders and by strata of cancer subtypes and smoking status. Antioxidant and other dietary intakes were assessed using a food frequency questionnaire (FFQ). During 1,233,096 person-years of follow-up between 1995 and 2013, a total of 1,690 lung cancer cases were newly diagnosed. In a multivariate regression model, while higher retinol intake was positively associated with overall lung cancer risk in men (HR 1.26; 95% CI 1.05-1.51; ptrend = 0.003), the estimates were more evident with small cell carcinoma (HR 1.92; 95% CI 1.13-3.24; ptrend < 0.001). Null associations were observed for other antioxidant vitamins. Our prospective study suggests that higher consumption of retinol may be associated with an increased risk of lung cancer in men, especially with small cell carcinoma, although confirmation is required.

A prospective study of immune and inflammation markers and risk of lung cancer among female never smokers in Shanghai.

There is a paucity of data on risk factors for lung cancer among never smokers. Here, we have carried out the first large study of circulating inflammation markers and lung cancer risk among female never smokers in Shanghai. A study of 248 lung cancer cases in female never smokers and 263 controls was nested within the Shanghai Women's Health Study (n = 75221), matched by dates of birth and blood collection (mean follow-up time = 7.5 years). Prediagnostic plasma levels of 65 inflammation markers were measured using a Luminex bead-based assay. Odds ratios (ORs) were estimated with multivariable logistic regression. Nine of 61 evaluable markers were statistically significantly associated with lung cancer risk among never smoking Chinese women (P-trend across categories <0.05). Soluble interleukin-6 receptor [sIL-6R; highest versus lowest category OR = 2.37; 95% confidence interval (CI) 1.40-4.02) and chemokine (C-C motif) ligand 2/monocyte chemotactic protein 1; (OR = 1.62; 95% CI 0.94-2.80) were associated with an increased risk of lung cancer, whereas interleukin (IL)-21 (OR = 0.53; 95%CI 0.31-0.93), chemokine (C-X3-C motif) ligand 1/fractalkine (OR = 0.54; 95% CI 0.30-0.96), soluble vascular endothelial growth factor receptor 2 (sVEGFR2, OR = 0.45; 95% CI 0.26-0.76), sVEGFR3 (OR = 0.53; 95% CI 0.32-0.90), soluble tumor necrosis factor receptor I (OR = 0.49; 95% CI 0.29-0.83), IL-10 (OR = 0.60; 95% CI 0.34-1.05) and C-reactive protein (OR = 0.63; 95% CI 0.37-1.06) were associated with a decreased risk. sIL-6R remained significantly associated with lung cancer risk >7.5 years prior to diagnosis. Markers involved in various aspects of the immune response were associated with subsequent lung cancer risk, implicating inflammation in the etiology of lung cancer among female never smokers.

Antiestrogen use in breast cancer patients reduces the risk of subsequent lung cancer: A population-based study

BackgroundThere is accumulating epidemiological and preclinical evidence that estrogen might be a driver of lung cancer. Breast cancer survivors can offer a unique patient cohort to examine the effect of antiestrogen therapy on lung cancer carcinogenesis because many of these women would have received long-term selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) as adjuvant treatment. Our hypothesis is that estrogens play a role in lung cancer development, and that antiestrogen therapy would affect the incidence of subsequent lung cancer among breast cancer survivors. MethodsUsing the Taiwan National Health Insurance (NHI) database, the study included 40,900 survivors of non-metastatic breast cancer after primary surgery, and most antiestrogen users complied well with the medication regimen. We evaluate the effect of antiestrogen therapy on the incidence of subsequent lung cancers. ResultsThis population-based study revealed that antiestrogen use in breast cancer patients was associated with a reduced risk of subsequent lung cancer in older patients (≥50 years) (HR 0.73, 95%CI 0.54–0.99) when compared with breast cancer survivors who did not use antiestrogens. ConclusionThe study supports the hypothesis that antiestrogen therapy modifies lung cancer carcinogenesis in older women. Further well-designed clinical trials to explore the potential of antiestrogens in lung cancer prevention and treatment would be worthwhile.

The effects of pulmonary diseases on histologic types of lung cancer in both sexes: a population-based study in Taiwan.

BackgroundThe associations between pulmonary diseases (asthma, chronic obstructive pulmonary disease [COPD], and tuberculosis [TB]) and subsequent lung cancer risk have been reported, but few studies have investigated the association with different histologic types of lung cancer.MethodsPatients newly diagnosed with lung cancer from 2004 to 2008 were identified from the National Health Insurance Research Database in Taiwan. Histologic types of lung cancer were further confirmed using the Taiwan Cancer Registry Database. Cox proportional hazards regression was used to calculate the hazard ratio (HR) of asthma, COPD, and TB and to estimate the risk of specific types of lung cancer.ResultsDuring the study period, 32,759 cases of lung cancer were identified from 15,219,024 insurants aged 20 years and older. In men and women, the adjusted HR estimates of squamous cell carcinoma were respectively 1.37 (95 % confidence interval [CI], 1.21–1.54) and 2.10 (95 % CI, 1.36–3.23) for TB, 1.52 (95 % CI, 1.42–1.64) and 1.50 (95 % CI, 1.21–1.85) for asthma, and 1.66 (95 % CI, 1.56–1.76) and 1.44 (95 % CI, 1.19–1.74) for COPD. Similarly, the adjusted HR estimates of adenocarcinoma were respectively 1.33 (95 % CI, 1.19–1.50) and 1.86 (95 % CI, 1.57–2.19) for TB, 1.13 (95 % CI, 1.05–1.21) and 1.18 (95 % CI, 1.09–1.28) for asthma, and 1.50 (95 % CI, 1.42–1.59) and 1.33 (95 % CI, 1.25–1.42) for COPD. The HRs of small cell carcinoma were respectively 1.24 (95 % CI, 1.01–1.52) and 2.23 (95 % CI, 1.17–4.25) for TB, 1.51 (95 % CI, 1.35–1.69) and 1.63 (95 % CI, 1.16–2.27) for asthma, and 1.39 (95 % CI, 1.26–1.53) and 1.78 (95 % CI, 1.33–2.39) for COPD.ConclusionsAsthma, COPD, and TB were associated with an increased risk of all major subtypes of lung cancer. The risk was the highest among women with TB.