Family History Of Lung Cancer Research Articles

Association Between Diabetes Risk Reduction Diet and Lung Cancer Risk in 98,159 Participants: Results From a Prospective Study.

PurposeTo evaluate the association between diabetes risk reduction diet (DRRD) score and the risk of lung cancer in a large population.MethodsData of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the Cox proportional hazards regression model for the association of DRRD score and lung cancer incidence in all included participants. Prespecified subgroup analyses were performed to evaluate whether the observed association was modified by age, sex, BMI, race/ethnicity, family history of lung cancer, smoking status and history of diabetes.ResultsA total of 98,159 participants were included in this study. The mean (SD) age of the study participants cohort at baseline was 65.5 (5.73) years old. The mean (SD) follow-up time was 8.83 (1.96) years. The mean (SD) score of DRRD was 26.82 (5.19), and ranged from 20.47 (2.3) to 33.65 (2.42) from the lowest quartile to the highest quartile of the DRRD score, inferring the possibility of highest through the lowest risk of type 2 diabetes. The calculated HRs showed there was a trend that higher quartile indicated lower risk of lung cancer after adjusted for covariates (HRQ4vsQ1: 0.85; 95% CI:0.73,0.98; p for trend =0.036). The inverse trend between higher DRRD score and the risk of squamous cell carcinoma was more evident (HRQ4vsQ1: 0.50; 95% CI:0.34,0.73; p for trend =0.002). The inverse association between DRRD score and the incidence of lung cancer was more pronounced in participants who had a clear family history of lung cancer (p for interaction=0.016).ConclusionA protective association between DRRD score and risk of lung cancer is obtained. People are encouraged to adhere to higher DRRD score in their daily diet. Further studies should be conducted to confirm the result and explore the mechanism.

Risk perception and disease knowledge in attendees of a community-based lung cancer screening programme

ObjectivesIn England, a risk-based approach is used to determine eligibility for lung cancer screening. Ensuring effective communication and counselling of risk is therefore increasingly important. In this study, we explore the perception of lung cancer risk in attendees of a community-based screening service, located in socio-economically deprived areas of Manchester. We analyse responses based on demographic variables, calculated risk score and screening eligibility. Materials and MethodsThe Manchester Lung Health Check (LHC) programme invited ever smokers, age 55–80, to a lung cancer risk assessment in which their 6-year risk was calculated (using the PLCOM2012 model). Those at high risk (PLCOM2012 score ≥ 1.51%) were eligible for low dose CT (LDCT) screening. Prior to their assessment, attendees were invited to complete the study questionnaire, which assessed absolute and comparative risk perception, disease knowledge (incidence, survival, and risk factors), lung cancer specific worry, and mental health. Results371 participants completed the questionnaire; 66% (n = 243) had linked clinical data. Perceived absolute risk was markedly higher than calculated risk (median: 20% vs. 1%; p < 0.001) and higher in women than men (25% vs. 15%; p = 0.001). There was no correlation between perceived absolute and calculated risk. Overall, 30% classified themselves at higher, and 21% at lower, lung cancer risk compared to others their age. Median PLCOM2012 score increased with perceived comparative risk (p = 0.004). Those eligible for screening were more likely to: classify themselves at higher comparative risk (41% vs. 21%; p < 0.0001), report lung cancer-specific worry (27% vs. 10%; p = 0.001) and have indications of depression (20% vs. 10%; p = 0.05). Family history of lung cancer was significantly associated with higher comparative risk (adjOR 4.03, 95%CI 1.74–9.3; p = 0.001). ConclusionEmploying comparative rather than absolute risk may assist risk counselling. Further research is required to determine the optimal approach to risk communication in this setting.

170P Clonal hematopoiesis in asymptomatic individuals enrolled in a lung cancer screening program

Clonal hematopoiesis of indeterminate potential (CHIP) is defined as a clonal accumulation of somatic mutations in hematopoietic stem cells in the absence of hematologic malignancy or other clonal disorders. CHIP has been associated with a higher risk of developing hematologic malignancies. Recently, CHIP has been linked to a family history of lung cancer (FHLC) in lung cancer patients. In the present study, we evaluated the association between clinical factors and CHIP in individuals enrolled in a lung cancer screening program.

Identification of heritable rare variants associated with early-stage lung adenocarcinoma risk.

BackgroundIn East Asia, the number of patients with adenocarcinoma, especially those presenting with ground-glass nodules (GGNs), is gradually increasing. Family aggregation of pulmonary GGNs is not uncommon; however, genetic predisposition in these patients remains poorly understood and identification of genes involved in the cause of these early-stage lung cancers might contribute to understanding of the underlying mechanisms and potential prevention strategies.MethodsFifty patients with early-stage lung adenocarcinoma (LUAD) presenting as GGNs and a first-degree family history of lung cancer (FHLC) from 34 independent families were enrolled into this study. Germline mutations of these patients were analyzed with whole exome sequencing (WES) and compared with age- and sex-matched 39 patients with sporadic lung cancer and 689 local healthy people. We used a stepwise variant filtering strategy, gene-based burden testing, and enrichment analysis to investigate rare but potentially pathogenic heritable mutations. Somatic tumor mutations were analyzed to consolidate germline findings.ResultsIn total, 1,571 single nucleotide variants (SNVs) and 238 frameshifts with a minor allele frequency (MAF) <0.01, which were rare, recurrent, and potentially damaging candidates, were finally identified through the filtering in the GGN cohort. Pathway analysis showed the extracellular matrix to be the top dysregulated pathway. Gene-based burden testing of these highly disruptive risk-conferring heritable variants showed that MSH5 [odds ratio (OR), 9.28, 95% confidence interval (CI): 2.49–35.87], MMP9 (OR, 8.11, 95% CI: 2.22–28.43), and CYP2D6 (OR, 8.09, 95% CI: 2.68–24.92) were significantly enriched in our cohort (P<0.05). The number of rare damaging germline variants in non-smoking patients was significantly higher than that of smoking-affected patients (Spearman’s ρ=−0.39, P=0.02).ConclusionsHeritable, potentially deleterious, and rare candidate variants of MSH5, MMP9 and CYP2D6 were significantly associated with early-stage LUAD presenting with GGNs. Nonsmoking patients likely have a higher genetic predisposition to this type of cancer than smoking-affected patients. These results have extended our understanding of the underlying mechanisms of early-stage LUAD.

One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study

Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China. A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans. Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p<0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p<0·0001) for participants in the screened group compared with those in the non-screened group. One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies. Ministry of Finance and National Health Commission of the People's Republic of China. For the Chinese translation of the abstract see Supplementary Materials section.

Lung Cancer Screening in Asbestos-Exposed Populations.

Asbestos exposure is the most important cause of occupational lung cancer mortality. Two large randomized clinical trials in the U.S. and Europe conclusively demonstrate that annual low-dose chest CT (LDCT) scan screening reduces lung cancer mortality. Age and smoking are the chief risk factors tested in LDCT studies, but numerous risk prediction models that incorporate additional lung cancer risk factors have shown excellent performance. The studies of LDCT in asbestos-exposed populations shows favorable results but are variable in design and limited in size and generalizability. Outstanding questions include how to: (1) identify workers appropriate for screening, (2) organize screening programs, (3) inform and motivate people to screen, and (4) incorporate asbestos exposure into LDCT decision-making in clinical practice. Conclusion: Screening workers aged ≥50 years with a history of ≥5 years asbestos exposure (or fewer years given intense exposure) in combination with either (a) a history of smoking at least 10 pack-years with no limit on time since quitting, or (b) a history of asbestos-related fibrosis, chronic lung disease, family history of lung cancer, personal history of cancer, or exposure to multiple workplace lung carcinogens is a reasonable approach to LDCT eligibility, given current knowledge. The promotion of LDCT-based screening among asbestos-exposed workers is an urgent priority.

Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

BackgroundAbout 15% of lung cancers in men and 53% in women are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in non-smokers in China.MethodsA large-sample size, population-based study was conducted under the framework of the Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set.ResultsA total of 214,764 eligible subjects were included, with a mean age of 55.19 years. Subjects were randomly divided into the training (107,382) and validation (107,382) sets. Elder age, being male, a low education level, family history of lung cancer, history of tuberculosis, and without a history of hyperlipidemia were the independent risk factors for lung cancer. Using these six variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.753, 0.752, and 0.755 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a moderate predictive discrimination, with the AUC was 0.668, 0.678, and 0.685 for the 1-, 3- and 5-year lung cancer risk.ConclusionsWe developed and validated a simple and non-invasive lung cancer risk model in non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in non-smokers.

Clonal Hematopoiesis Mutations in Patients with Lung Cancer Are Associated with Lung Cancer Risk Factors.

Clonal hematopoiesis (CH) is a phenomenon caused by expansion of white blood cells descended from a single hematopoietic stem cell. While CH can be associated with leukemia and some solid tumors, the relationship between CH and lung cancer remains largely unknown. To help clarify this relationship, we analyzed whole-exome sequencing (WES) data from 1,958 lung cancer cases and controls. Potential CH mutations were identified by a set of hierarchical filtering criteria in different exonic regions, and the associations between the number of CH mutations and clinical traits were investigated. Family history of lung cancer (FHLC) may exert diverse influences on the accumulation of CH mutations in different age groups. In younger subjects, FHLC was the strongest risk factor for CH mutations. Association analysis of genome-wide genetic variants identified dozens of genetic loci associated with CH mutations, including a candidate SNP rs2298110, which may promote CH by increasing expression of a potential leukemia promoter gene OTUD3. Hundreds of potentially novel CH mutations were identified, and smoking was found to potentially shape the CH mutational signature. Genetic variants and lung cancer risk factors, especially FHLC, correlated with CH. These analyses improve our understanding of the relationship between lung cancer and CH, and future experimental studies will be necessary to corroborate the uncovered correlations. SIGNIFICANCE: Analysis of whole-exome sequencing data uncovers correlations between clonal hematopoiesis and lung cancer risk factors, identifies genetic variants correlated with clonal hematopoiesis, and highlights hundreds of potential novel clonal hematopoiesis mutations.

Association between family history and lung cancer risk among Chinese women in Singapore

Risk factors of lung cancer unrelated to smoking are not well-studied, especially among women. Family history has been shown to play a role in predisposing individuals to lung cancer, but this relationship has not been investigated in the Southeast Asian population. A total of 1159 women were recruited in a case–control study conducted in public hospitals in Singapore from 2005 to 2008. After excluding participants with incomplete family history information, 374 cases and 785 controls remained in the final analysis. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for potential confounders. Overall, family history of lung cancer was associated with a higher risk for lung cancer (aOR 2.08, 95% CI 1.25–3.47). When stratified by smoking status, a significant association was observed among never-smokers (aOR 2.78, 95% CI 1.57–4.90). Further stratification by fruit consumption identified a significant association between family history of lung cancer and higher risk of lung cancer among never-smokers who had low fruit consumption (aOR 3.09, 95% CI 1.37–7.01). Our findings suggest that family history of lung cancer is a significant risk factor for lung cancer in Singaporean Chinese women, especially among never-smokers.

Previous Extrapulmonary Malignancies Impact Outcomes in Patients With Surgically Resected Lung Cancer.

Background: As the overall survival of patients with cancer continues to improve, the incidence of second primary malignancies seems to be increasing. Previous studies have shown controversial results regarding the survival of patients with primary lung cancer with previous extrapulmonary malignancies. This study aimed to determine the clinical picture and outcomes of this particular subgroup of patients.Materials and Methods: We included 2,408 patients who underwent pulmonary resection for primary lung cancer at our institute between January 1, 2011 and December 30, 2017 in this retrospective study. Medical records were extracted and clinicopathological parameters and postoperative prognoses were compared between patients with lung cancer with and without previous extrapulmonary malignancies.Results: There were 200 (8.3%) patients with previous extrapulmonary malignancies. Breast cancer (30.5%), gastrointestinal cancer (17%), and thyroid cancer (9%) were the most common previous extrapulmonary malignancies. Age, sex, a family history of lung cancer, and preoperative carcinoembryonic antigen levels were significantly different between the two groups. Patients with previous breast or thyroid cancer had significantly better overall survival than those without previous malignancies. Conversely, patients with other previous extrapulmonary malignancies had significantly poorer overall survival (p < 0.001). The interval between the two cancer diagnoses did not significantly correlate with clinical outcome.Conclusion: Although overall survival was lower in patients with previous extrapulmonary malignancies, previous breast or thyroid cancer did not increase mortality. Our findings may help surgeons to predict prognosis in this subgroup of patients with primary lung cancer.

P61.01 Intelligence Assistant Million Early-Stage Lung Cancer Research Program in China

To improve the prognosis of the lung cancer population in China, smoking control and the proposal of lung cancer prevention and treatment are very urgent. However, in 2015, the lung cancer condition was still severe. The data published by He Jie et al. on CA Cancer demonstrated that there were 4.292 million new diagnosed cases and 2.814 million deaths in China. Lung cancer is the No. 1 incidence cancer in China and the top cause of cancer death. To change the current condition of high incidence, high mortality, and low 5-year overall survival rate in China, we established the Chinese Alliance Against Lung Cancer and organized and propagated the 'Chinese expert consensus of pulmonary nodules’. In this consensus, the screening criteria for lung cancer was: elder than 40 years old and exist one of the following risk factors: 1) smoking more than 400 cigarette year (or 20 package year); or ex-smoker more than 400 cigarette year (or 20 package year), quit smoking less than 15 years; 2) high risk on the exposure to professional toxic materials (such as asbestos, beryllium, uranium, and radon); 3) comorbidly of chronic obstructive pulmonary disease, diffused pulmonary fibrosis or history of tuberculosis; 4) history of a malignant tumor or family history of lung cancer. The criteria on the age have significantly improved the early diagnosis of lung cancer. For example, in Zhongshan Hospital Fudan University (Table 1), from January 2014 to June 2019, 16,400 cases with pulmonary nodules received surgical treatment. The pathological diagnosis confirmed 9,980 cases (60.8%) were in the early stage of lung cancer. The average age of surgical patients decreased from 63 years old (2014) to 50 years old (2019). These cases could reach ten years of overall survival year by over 90%, significantly surpassing the current 20% on 5-year overall survival rate. Most significantly, the 9,800 patients cost 800 million RMB. Suppose we calculated the social contribution by working years. In that case, decreasing to 50-year-old when they received surgery could save 10 to 15 years on working, increase 1,000 million incomings and 100 million taxes for the county. In our real-world clinical experience, if we start screening lung cancer at age 50, we will see misdiagnosis on 1975 cases of pulmonary nodule patients younger than 50 years old. By now, there are more than 50 hospitals have registered in this program, and we are waiting for more real-world study-based data.

Using social media and direct marketing as a platform to increase awareness of lung cancer screening in a Hispanic urban population in the post-COVID period.

339 Background: Uptake in lung cancer screening (LCS) in high-risk patients including minority populations has been low despite efforts to increase awareness in the community. During the COVID pandemic, most LCS programs were temporarily stopped and, in the months to follow experienced a significant reduction in referrals. Platforms including social media and direct mail marketing can provide a valuable tool to enhance patient engagement related to LCS and engagement of Hispanic populations who are active consumers of digital media. The objective of this study was to assess the short-term effectiveness of a targeted LCS digital and direct marketing campaign to increase visits to the institutional online educational content and referrals to a LCS program. Methods: A LCS marketing campaign including social media utilizing Facebook and Instagram platforms with programmatic banners, boosted organic social media posts, plus direct mail-in marketing in Spanish and English was started in the post-COVID period. A CRM (customer-relationship management) software was used to target adults ages 50-80, current or former smokers, who speak English and/or Spanish in the Miami tri-county area over a three-month period by a direct-mail campaign. Other campaign targeting qualifications included family history of lung cancer, and additional lung cancer risk factors including asbestos, chronic obstructive pulmonary disease, or emphysema. The CRM Direct mail campaign was sent 87,000 leads by postcard and 65,810 leads by email. Primary outcomes measures were visits to the University of Miami institutional LCS Web page, LDCT ambulatory referrals, and scheduled initial LDCT exams. Study period was baseline pre-COVID period (6/1/2019-12/31/2019), COVID-period (3/1/2020-9/31/2020) and digital awareness campaign in the post-COVID period (12/1/2020-5/31/2020). Results: Unique pageviews to the institutional LCS web pages were significantly higher during the digital awareness campaign compared to the pre-COVID period (8,805 vs 230 pageviews) with a high bounce rate during the campaign period of 79% and average time in site of 2:21 minutes. Mean scheduled initial LDCT volumes per month during the pre-COVID period were 12.4 (SD 4.6), versus 4.1 (SD 2.5) during the COVID period. There was a 3-fold increase in initial LDCT scans during the initial campaign period from 4.1 in the COVID period to 11.6 (p &lt;.001). The mean number of LDCT ambulatory referrals doubled from 17.5 in the COVID period to 34.2 in the campaign period (p &lt; 0.001). Conclusions: Implementation of a targeted LCS digital awareness campaign and direct mail marketing was associated with increased visits to institutional education Web pages, ambulatory referrals, and initial LDCT exams. Digital platforms are an important tool to enhance awareness of lung cancer screening in high-risk populations and Hispanics.

Using community health advisors to increase lung cancer screening awareness in the Black Belt: A pilot study.

117 Background: Disease stage at the time of diagnosis is the most important determinant of prognosis for lung cancer. Despite demonstrated effectiveness of lung cancer screening (LCS) in reducing lung cancer mortality, early detection continues to elude populations with the highest risk for lung cancer death. Consistent with the national rate, current screening rate in Alabama is dismal at 4.2%. While public awareness of LCS may be a likely cause there are no studies that have thoroughly evaluated current knowledge of LCS within the Deep South. Therefore, we measured (LCS) knowledge before and after receiving education delivered by Community Health Advisors (CHAs) among high-risk individuals living in medically-underserved communities of Alabama and to determine impact of psychological, demographic, health status and cognitive factors on rate of lung cancer screening participation. Methods: Participants were recruited from one urban county and six rural Black Belt counties (characterized by poverty, rurality, unemployment, low educational attainment and disproportionate lack of access to health services).100 individuals (i) aged between 55 to 80 years (ii) Currently smoke or have quit within the past 15 years. (iii) Have at least a total of 30-pack-year smoking history were recruited. Knowledge scores to assess lung cancer knowledge were calculated. Paired t-test was used to assess pre and post knowledge score improvement. Screening for lung cancer was modeled as a function of predisposed factors (age, gender, insurance, education, fatalism, smoking status, and history of family lung cancer). Results: Average age was 62.94(SD = 6.28), mostly female (54%); mostly current smokers (53% ). Most participants (80.85%) reported no family history of cancer. Fatalism was low, with a majority of the participants disagreeing that a cancer diagnosis is pre-destined (67.7%) and that there are no treatments for lung cancer (88.66%). Overall, lung cancer knowledge increased significantly from baseline of 4.64(SD = 2.37) to 7.61(SD = 2.26). Of the 100 participants, only 23 underwent screening due to lack of access to primary care providers and reluctance of PCPs to provide referral to LCS. 65% of those who were screened reported family history of lung cancer. Regression analysis revealed no significant association between risk factors and the decision to get screened by participants. Conclusions: Our study demonstrates that while CHA delivered education initiatives increases lung cancer screening knowledge, there are significant structural barriers that prohibit effective utilization of LCS which needs to be addressed.

P61.06 Participants With Family History of Cancer Have a Higher Participation Rate of Low-Dose Computed Tomography for Lung Cancer Screening

Family history of cancer is an important risk factor for lung cancer. Studies have shown that it may also affect the willingness to lung cancer screening. To describe the low-dose computed tomography (LDCT) participation rate with a history of common cancers in a population-based screening program. The analysis was conducted in the context of the Cancer Screening Program in Urban China, which recruited 282,377 eligible participants aged 40-74 years from 8 cities in Henan province from 2013 to 2019. A total of 55,428 participants were evaluated to be high-risk for lung cancer by an established risk score system and were subsequently recommended for LDCT. In this study, we calculated the overall and group-specific participation rates by a family history of common cancers, as well as compared the differences in participation rates between different groups. Obtain odds ratios (ORs) and 95% CIs derived by multiple logistic regression model. Of 55,428 with high-risk for lung cancer, 22,260 subjects undertook LDCT (participation rate of 40.16%). We found that a family history of lung cancer, esophageal cancer, stomach cancer, liver cancer, and colorectal cancer were associated with increased participation in LDCT screening. The odds of participants with a family history of one cancer, two cancers, three cancers, and four or more cancers undertaking LDCT screening were 0.9-fold, 1.7-fold, 1.8-fold, and 2.5-fold higher than participants with no family history of cancer (OR: 1.88, 95% CI: 1.80-1.96; OR: 2.65, 95% CI: 2.51-2.79; OR: 2.83, 95% CI: 2.64-3.04; OR: 3.46, 95% CI: 3.15-3.79), respectively. Compared with those without a history of cancer, as the number of cancer family history increases, compliance gradually increases (P<0.001). There was room for improvement regarding lung cancer screening yield given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may be a choice.

Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study.

Research on glucosamine shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. We aimed to explore the relationship between use of glucosamine and risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study. Participants were enrolled between 2006 and 2010 and followed-up to 2020. The Cox proportional hazards model was used to assess the relationship between glucosamine use and risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings. 439 393 participants (mean age 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. 82 603 (18.80%) participants reported regular use of glucosamine at baseline. During follow-up, 1971 (0.45%) lung cancer events were documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio (HR) 0.84, 95% CI 0.75-0.92; p<0.001) and lung cancer mortality (HR 0.88, 95% CI 0.81-0.96; p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared with those without a family history. Regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.

Lung cancer risk in non-smoking females with a familial history of cancer: a multi-center prospective cohort study in China

Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown. We sought to determine the relationship between a family history of cancer and lung cancer risk among Chinese non-smoking females based on a multi-center prospective population-based cohort study involving 547,218 individuals between 2013 and 2019. A total of 1620 lung cancer cases occurred during a median follow-up of 3.9 years. Multivariable Cox regression showed that a family history of lung cancer in first-degree relatives significantly increased the risk of lung cancer (HR: 1.50, 95%CI: 1.29, 1.75, P <0.001). Relative to those with no relatives affected, the risk of lung cancer was 51% higher in females with one relative affected (HR: 1.51, 95%CI: 1.29-1.76, P <0.001), 123% higher in females with two relatives affected (HR: 2.23, 95%CI: 1.57-3.15, P <0.001) and 143% higher in females with three or more relatives affected (HR: 2.43, 95%CI: 1.21-4.91, P =0.013). Two nested case control studies stratified by age at diagnosis were conducted to verify potential disparities in this association between the early or late onset of lung cancer. A family history of lung cancer in first-degree relatives was significantly correlated with an elevated risk of lung cancer for both cases before and after age 65 (OR: 1.36, 95%CI: 1.07-1.74, P =0.013; OR: 1.64, 95%CI: 1.15-2.33, P =0.006). Our analysis confirmed the importance of familial history of cancers on lung cancer risk in non-smoking females and highlighted the possibility of interaction between genetic and environmental effect on lung cancer.

Combined effects of lung disease history, environmental exposures, and family history of lung cancer to susceptibility of lung cancer in Chinese non-smokers

BackgroundAlthough cigarette smoking is a major risk factor for lung cancer, the incidence rate of lung cancer among non-smokers is notable. The etiology and potential mechanism of non-smoker lung cancer are worthy of further research. This study was designed to explore the collective effects of environmental factors and the relationship between environmental exposure index (EEI) and lung cancer among non-smokers by evaluating the joint effects among lung disease history, environmental factors, and family history of lung cancer without smoking confounders.MethodsA total of 767 never-smoked lung cancer cases and 767 sex- and age-matched controls were selected from the department of Thoracic Surgery and Respiratory Medicine of three hospitals in Fujian, China. We used two methods to develop the EEI according to 12 statistically significant environmental risk factors. Restricted cubic spline (RCS) was applied to analyze the non-linear relationship between EEI and lung cancer in non-smokers. Combined effects, additive interaction, and multiplicative interaction were assessed among lung disease history, EEI, and family history of lung cancer to estimate susceptibility to develop lung cancer.ResultsLung disease history, especially asthma, was significantly associated with an increased risk of lung cancer with an odds ratio (OR) for asthma history of 14.720 (95% CI: 1.877–115.449). Family history of lung cancer was related to susceptibility of lung cancer (OR = 3.347, 95% CI: 1.930–5.806). According to type of relatives and cancer, a parental or children’s history and a sibling’s history of lung cancer were significantly associated with an increased risk of lung cancer. The positive association between EEI and lung cancer was apparently stronger in those with lung disease history or family lung cancer history. Furthermore, there was a addictive interaction between EEI and lung disease history, and a possibly addictive interaction between EEI and family lung cancer history on development of lung cancer.ConclusionsThere were combined effects among lung disease history, environmental exposures, and family history of lung cancer toward susceptibility to lung cancer in Chinese non-smokers. Non-smokers who had a family history of lung cancer were at higher risk of lung cancer than non-smokers who had lung disease history. Non-smokers with family cancer history may obtain benefits from removal of environmental exposures and active treatment of lung disease.

Lung Cancer Risk in Suspicious Lung Nodules With Negative Positron Emission Tomography

BackgroundLung CT Screening Reporting and Data System (LungRADS) Category 4 represents lung nodules with the highest likelihood of cancer. For LungRADS-4 lesions, if positron emission tomography (PET) is negative, no uniform guideline currently exists on subsequent follow-up, particularly whether the surveillance interval can be extended. We sought to investigate the incidence of cancer, our surveillance practice, and any clinical factors associated with cancer in this patient subset. MethodsWe retrospectively stratified LungRADS-4 patients screened at our institution from March 2015 to February 2019 into subgroups: PET positive, PET negative, and no PET performed. PET negativity was defined as the absence of a radiologist’s suspicion or a maximum standardized uptake value at or below the mediastinal value. ResultsOf the 191 LungRADS-4 patients identified, 67 (35.1%) met the criteria for PET negativity. Cancer was diagnosed in 28.8% of the entire cohort (55/191), 77.8% of the PET-positive subgroup (35/45), 22.4% of the PET-negative subgroup (15/67), and 6.3% of the no PET subgroup (5/79). The most common follow-up modality after a negative PET was a computed tomography (47/67, 70.1%), with a median interval of 3.1 months. Clinical variables including nodule location/size, chronic obstructive pulmonary disease, family history of lung cancer, pack-years, and number of years quit in former smokers were not significantly associated with greater cancer risk among the PET-negative subgroup. ConclusionsFor LungRADS-4/PET-negative lesions the cancer risk remained high despite a lack of activity on PET. As such we believe the current surveillance practice of continuing to follow LungRADS-4/PET-negative patients as LungRADS-4 patients is appropriate.

Risk Factors for Lung Cancer in an Underrepresented Safety-Net Screening Cohort

Introduction/BackgroundThe USPSTF (United States Preventive Services Task Force) guidelines suggest criteria centering on smoking status and age to select patients for lung cancer screening. Despite the significant advances in screening with low-dose computed tomography (LDCT), cancer detection rate is low (1.1%), highlighting the need to investigate possible ways to refine the current lung cancer screening strategy. Our aim was to determine clinical risk factors predictive of lung cancer in an urban safety-net hospital. Materials and MethodsWe performed a retrospective chart review of 2847 patients who received LDCT screening for lung cancer between 3/1/2015 and 12/31/2019. Patient demographics and medical history were collected. A bivariate logistic regression was used to evaluate predictors of lung cancer. ResultsCompared to the National Lung Cancer Screening Trial (NLST) population, our screening cohort had significantly more African Americans (38.2% vs. 4.5%, P < .0001), more obesity (32.7% vs. 28.3%, P < .0001), and higher rates of chronic obstructive pulmonary disease (COPD) (45.9% vs. 5.0%, P < .0001). The strongest predictors of lung cancer were COPD (odds ratio [OR] = 2.14, P < .0001) and a family history of lung cancer (OR = 2.77, P < .0001). Age (OR = 1.04, P< .001) and pack years (OR = 1.01, P< .001) were less predictive. ConclusionA diagnosis of COPD and family history of lung cancer were most predictive of lung cancer in a screening cohort at our urban safety-net hospital. Future studies should focus on whether inclusion of these additional risk-factors improves proportion of lung cancer detected via screening.

High-Ambient Air Pollution Exposure Among Never Smokers Versus Ever Smokers With Lung Cancer

IntroductionAir pollution may play an important role in the development of lung cancer in people who have never smoked, especially among East Asian women. The aim of this study was to compare cumulative ambient air pollution exposure between ever and never smokers with lung cancer. MethodsA consecutive case series of never and ever smokers with newly diagnosed lung cancer were compared regarding their sex, race, and outdoor and household air pollution exposure. Using individual residential history, cumulative exposure to outdoor particulate matter (PM2.5) in a period of 20 years was quantified with a high-spatial resolution global exposure model. ResultsOf the 1005 patients with lung cancer, 56% were females and 33% were never smokers. Compared with ever smokers with lung cancer, never smokers with lung cancer were significantly younger, more frequently Asian, less likely to have chronic obstructive pulmonary disease or a family history of lung cancer, and had higher exposure to outdoor PM2.5 but lower exposure to secondhand smoke. Multivariable logistic regression analysis revealed a significant association with never-smoking patients with lung cancer and being female (OR = 4.01, 95% confidence interval [CI]: 2.76–5.82, p < 0.001), being Asian (ORAsian versus non-Asian = 6.48, 95% CI: 4.42–9.50, p < 0.001), and having greater exposure to air pollution (ORln_PM2.5 = 1.79, 95% CI: 1.10–7.2.90, p = 0.019). ConclusionsCompared with ever-smoking patients with lung cancer, never-smoking patients had strong associations with being female, being Asian, and having air pollution exposures. Our results suggest that incorporation of cumulative exposure to ambient air pollutants be considered when assessing lung cancer risk in combination with traditional risk factors.