Lower Lung Cancer Research Articles

Adherence to lifelines diet is associated with lower lung cancer risk in 98,459 participants aged 55 years and above: a large prospective cohort study

BackgroundLifelines Diet Score (LLDS) was developed based on the 2015 Dutch Dietary Guidelines and current international scientific evidence. As a dietary quality assessment tool, the LLDS aims to evaluate the association between the Lifeline diet and the risk of chronic diseases. However, the evidence linking LLDS to lung cancer risk is currently limited.ObjectiveOur objective was to explore whether adherence to the LLDS is associated with reduced incidence and mortality of lung cancer, including its major histological subtypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).MethodsData for this research were sourced from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. The LLDS for each participant was calculated based on responses to the dietary history questionnaire (DHQ), and subsequently analyzed after being categorized into quintiles. The Cox proportional hazards regression model was utilized to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for both the incidence and mortality of lung cancer, SCLC and NSCLC. Additionally, stratified analyses were conducted to ascertain possible effect modifiers, and several sensitivity analyses were performed to evaluate the robustness of the findings.ResultsDuring the mean follow-up periods of 8.8 years for incidence and 15.1 years for mortality, we identified 1,642 new cases and 1,172 related deaths from lung cancer. Participants in the highest quartiles of LLDS compared to those in the lowest exhibited a reduced incidence (HRQ4:Q1 = 0.80, 95% CI = 0.68–0.94, P for trend = 0.003) and mortality (HRQ4:Q1 = 0.81, 95%CI = 0.67–0.98, P for trend = 0.009) of lung cancer. Furthermore, this negative association remained for SCLC incidence (HRQ4:Q1 = 0.55, 95% CI = 0.35–0.87, P for trend = 0.002) and mortality (HRQ4:Q1 = 0.42, 95% CI = 0.25–0.70, P for trend <0.001). The association between LLDS and the incidence and mortality of lung cancer is not influenced by pre-defined potential effect modifiers (all Pinteraction > 0.05). The sensitivity analyses substantiated the robustness of the results.ConclusionIn conclusion, our research indicates that among 98,459 U.S. adults aged 55 and older, adherence to the LLDS is linked to a diminished incidence and mortality of lung cancer.

Abstract A071: County-level racial and ethnic diversity index and cancer mortality in the U.S.

Abstract Background: The United States is experiencing a demographic trend of increasing racial and ethnic diversity. While persistent racial and ethnic disparities in cancer mortality are well documented, little is known about the impact of racial and ethnic diversity on cancer outcomes in the United States. Purpose: We examined associations between the U.S. county-level racial & ethnic diversity index and age-adjusted cancer mortality rates. We also assessed whether associations differed by geographic region, persistent poverty, and rurality. Methods: We used the U.S. Census Bureau’s 2020 Racial and Ethnic Diversity Index, which estimates the chance that two people chosen at random will be from different racial and ethnic groups. The diversity index was calculated at the county-level and categorized as follows: less than 35% (lowest), 35.0 to 44.9%, 45.0 to 54.9%, 55.0 to 64.9% and 65.0% or more (highest). We described county- level sociodemographic characteristics according to the diversity index categories. We calculated mean and standard errors of the county-level age-adjusted cancer mortality rates per 100,000 from 2016-2020 (overall and by site for the top four sites for cancer mortality) across the diversity index categories. We used multivariable linear regression models to examine associations between racial and ethnic diversity and cancer mortality, overall and by cancer site. We also assessed models stratified by geographic region (U.S. Census regions), persistent poverty and rurality. Results: Counties with more racial and ethnic diversity had a younger median age, a higher proportion of college graduates, and were less likely to be rural. Cancer mortality rates per 100,000 were lower in the most vs. least diverse counties, overall (144.7 vs. 164.6), and for lung (32.5 vs. 44.8), and colorectal cancer (13.0 vs. 15.6). In adjusted models, the highest vs. lowest racial and ethnic diversity was associated with a 7.25 decrease in overall cancer mortality rates (95% CI: -10.5 to -4.0), a 6.55 decrease in lung cancer mortality (95% CI: -8.0 to -5.1) and a 1.49 increase in breast cancer mortality (95% CI: 0.7 to 2.3). The diversity index was not associated with colorectal cancer mortality or pancreatic cancer mortality in adjusted models. Inverse associations of diversity index and overall cancer mortality were strongest in the South Census region (b=-13.0, 95% CI: -17.5 to -8.4), in non-persistent poverty counties (b=-9.0, 95% CI: -12.4 to -5.5), and in rural counties (b=-8.6, 95% CI: -13.2 to -4.1). Conclusions: Greater racial and ethnic diversity was associated with lower overall cancer mortality and lung cancer mortality rates, although it was associated with significantly higher breast cancer mortality rates. Findings help elucidate whether and how social factors may differentially impact subgroups of the population to influence cancer mortality. This study addresses an urgent need to explore contextual factors that may shape racial and ethnic disparities at the population level. Citation Format: Kelly A. Hirko, Breanna Greteman, Sabrina Ford, Sarah H. Nash. County-level racial and ethnic diversity index and cancer mortality in the U.S. [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A071.

Racial and ethnic differences in second primary lung cancer risk among lung cancer survivors.

Recent therapeutic advances have improved survival among lung cancer (LC) patients, who are now at high risk of second primary lung cancer (SPLC). Hispanics comprise the largest minority in the United States, who have shown a lower LC incidence and mortality than other races, and yet their SPLC risk is poorly understood. We quantified the SPLC incidence patterns among Hispanics vs other races. We used data from the Multiethnic Cohort, a population-based cohort of 5 races (African American, Japanese American, Hispanic, Native Hawaiian, and White), recruited between 1993 and 1996 and followed through 2017. We identified patients diagnosed with initial primary lung cancer (IPLC) and SPLC via linkage to Surveillance, Epidemiology, and End Resultsregistries. We estimated the 10-year cumulative incidence of IPLC (in the entire cohort) and SPLC (among IPLC patients). A standardized incidence ratio (SIR) was calculated as the ratio of SPLC-to-IPLC incidence by race and ethnicity. Among 202 692 participants, 6788 (3.3%) developed IPLC over 3 871 417 person-years. The 10-year cumulative IPLC incidence was lower among Hispanics (0.80%, 0.72 to 0.88) vs Whites (1.67%, 1.56 to 1.78) or Blacks (2.44%, 2.28 to 2.60). However, the 10-year SPLC incidence following IPLC was higher among Hispanics (3.11%, 1.62 to 4.61) vs Whites (2.80%, 1.94 to 3.66) or Blacks (2.29%, 1.48 to 3.10), resulting in a significantly higher SIR for Hispanics (SIR = 8.27, 5.05 to 12.78) vs Whites (SIR = 5.60, 4.11 to 7.45) or Blacks (SIR = 3.48, 2.42 to 4.84; P < .001). Hispanics have a higher SPLC incidence following IPLC than other races, which may be potentially due to better survival after IPLC and extended duration for SPLC development. Continuing surveillance is warranted to reduce racial disparities among LC survivors.

Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania.

Background and Objectives: This study aimed to evaluate the potential chemopreventive effect of antidiabetic medications, specifically metformin and pioglitazone, on lung cancer in patients with type 2 diabetes mellitus (T2DM). Additionally, the potential dose-response relationship for metformin use was analyzed. Methods: We conducted a retrospective cohort study utilizing comprehensive national health insurance and cancer registry databases to gather a large cohort of T2DM patients. Cox proportional hazards regression models were used to assess the risk of lung cancer across different antidiabetic medication groups, adjusting for potential confounders such as age and gender. A dose-response analysis was conducted for metformin users. Results: Our results indicated that metformin users had a significantly lower lung cancer risk than the reference group (HR = 0.69, 95% CI [0.55-0.86], p = 0.001). The risk reduction increased with higher cumulative metformin doses: a metformin cumulative dose between 1,370,000 and 2,976,000 had an HR of 0.61 (95% CI [0.49-0.75], p < 0.001) vs. cumulative metformin dose >2,976,000 which had an HR of 0.35 (95% CI [0.21-0.59], p < 0.001). No significant association between pioglitazone use and the risk of lung cancer was found (HR = 1.00, 95% CI [0.25-4.02]). Conclusions: This study shows that metformin may have a dose-dependent chemopreventive effect against lung cancer in T2DM, while the impact of pioglitazone remains unclear and requires further investigation.

Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk

BackgroundSoy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. MethodsA two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. ResultsA nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57–0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). ConclusionsWe identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

Enhancing early detection of lung cancer: A strategic initiative to boost screening rates among patients.

e22512 Background: Lung cancer is the top cause of cancer death in the U.S. Despite LDCT screenings reducing mortality, uptake is low in Alabama and nationally (6% vs. 4.5%). The U.S. Preventive Services Task Force recommends annual LDCT for certain high-risk adults, but factors like awareness, access, and policy affect screening rates. Alabama's situation is worsened by rural disparities and socioeconomic issues. Infirmary Health is the largest private, not for profit health care system in the state of Alabama. This study focuses on evaluating LDCT screening in a selected clinic of our health care system, pinpointing obstacles to adherence, and seeking ways to boost screenings to lower lung cancer mortality through early detection. Methods: As part of the Summer 2023 ASCO Quality Training Program we adopted a QI approach to increase LDCT lung cancer screening. It began by assessing baseline screening rates and staff knowledge, then created problem and aim statements. The team conducted root cause analysis, used a Pareto chart for issue prioritization, and employed a Priority Pay-off Matrix to focus on impactful, feasible issues. The Plan-Do-Study-Act (PDSA) cycle was then used to develop, test, and implement interventions, ensuring strategic alignment and effective monitoring of outcomes to enhance screening rates. Results: From January to July 2023, the Infirmary Health -Hillcrest clinic had a low 10.53% LDCT screening rate (system wide 6%, this clinic was selected due to it's highest screening rate), leading to late-stage lung cancer diagnoses and higher mortality. To address this, a goal was set to triple the screening rate to 30% by December 2023. Key barriers identified were staff and patient knowledge about lung cancer screening and a cumbersome LDCT ordering process. A PDSA cycle initiated between September and December 2023, firstly focused on Patient/Clinic Education, increasing screening rates by simplifying the process—removing doctor signature requirements and enhancing staff knowledge through meetings and informative flyers. The subsequent phase introduced a Nurse Navigator, who further increased screenings through prescreening, staff reminders, and on-site visits. By December of 2023 the LDCT screening rate was increased from baseline 10.53% to 33.3%. Conclusions: Through identifying and addressing key issues like education, faulty process and nurse navigation we successfully elevated LDCT screening rates. This study highlights the benefit of participating in a structured quality training program. [Table: see text]

The Impact of Model Assumptions on Personalized Lung Cancer Screening Recommendations.

Recommendations regarding personalized lung cancer screening are being informed by natural-history modeling. Therefore, understanding how differences in model assumptions affect model-based personalized screening recommendations is essential. Five Cancer Intervention and Surveillance Modeling Network (CISNET) models were evaluated. Lung cancer incidence, mortality, and stage distributions were compared across 4 theoretical scenarios to assess model assumptions regarding 1) sojourn times, 2) stage-specific sensitivities, and 3) screening-induced lung cancer mortality reductions. Analyses were stratified by sex and smoking behavior. Most cancers had sojourn times <5 y (model range [MR]; lowest to highest value across models: 83.5%-98.7% of cancers). However, cancer aggressiveness still varied across models, as demonstrated by differences in proportions of cancers with sojourn times <2 y (MR: 42.5%-64.6%) and 2 to 4 y (MR: 28.8%-43.6%). Stage-specific sensitivity varied, particularly for stage I (MR: 31.3%-91.5%). Screening reduced stage IV incidence in most models for 1 y postscreening; increased sensitivity prolonged this period to 2 to 5 y. Screening-induced lung cancer mortality reductions among lung cancers detected at screening ranged widely (MR: 14.6%-48.9%), demonstrating variations in modeled treatment effectiveness of screen-detected cases. All models assumed longer sojourn times and greater screening-induced lung cancer mortality reductions for women. Models assuming differences in cancer epidemiology by smoking behaviors assumed shorter sojourn times and lower screening-induced lung cancer mortality reductions for heavy smokers. Model-based personalized screening recommendations are primarily driven by assumptions regarding sojourn times (favoring longer intervals for groups more likely to develop less aggressive cancers), sensitivity (higher sensitivities favoring longer intervals), and screening-induced mortality reductions (greater reductions favoring shorter intervals). Models suggest longer screening intervals may be feasible and benefits may be greater for women and light smokers. Natural-history models are increasingly used to inform lung cancer screening, but causes for variations between models are difficult to assess.This is the first evaluation of these causes and their impact on personalized screening recommendations through easily interpretable metrics.Models vary regarding sojourn times, stage-specific sensitivities, and screening-induced lung cancer mortality reductions.Model outcomes were similar in predicting greater screening benefits for women and potentially light smokers. Longer screening intervals may be feasible for women and light smokers.

Serum lipid levels, genetic risk, and lung cancer incidence: A large prospective cohort study.

Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk. 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk. Higher level of apolipoprotein A were significantly correlated with lower lung cancer risk. A inverse-J-shaped relationship between HDL and incident lung cancer was found. Individuals with low total cholesterol, HDL, LDL, apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL (RERI:0.25, 95%CI: 0.04-0.46), as well as the interaction effect of high PRS and low apolipoprotein B (RERI:0.28, 95%CI: 0.07-0.48), were both greater than the sum of their individual effects on lung cancer risk. Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk. Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.

A middle lobe sparing sleeve resection versus bilobectomy for right lower central non-small cell lung cancer: a retrospective propensity score matched cohort study

ObjectivesThe right lower sleeve lobectomy is a rarely performed major lung resection.This study aims to evaluate the safety and effectiveness of this procedure by comparing to right lower bilobectomy in non-small cell lung cancer patients.MethodsWe retrospectively reviewed a prospective database of non-small cell lung cancer patients who underwent right lower sleeve lobectomy (group S) or right lower bilobectomy (group B) from January 2014 to January 2020 in Shanghai Pulmonary Hospital. Propensity score matching method was applied to balance confounders between the two groups, resulting in 41 matched pairs.The analysis was performed to compare perioperative outcomes, long-term survival, and postoperative pulmonary volume between the two groups.ResultsNo significant differences in the characteristics were observed between the two matched groups.Major postoperative complications developed in 31.7% of the patients in group B and 12.1% of the patients in group S (P = 0.032).Intervention rate for surgical residual cavity in group B is significantly higher than those patients in group S(21.9%vs7.3%,p = 0.037).The postoperative right lateral and overall lung volume in group S were both significantly larger than that in group B (P = 0.026,P = 0.001,respectively).ConclusionsCompared to bi-lobectomy, a middle lobe sparing sleeve resection obtains a less prevalence of major complications, smaller postoperative residual air space and similar long-term survival for selected central right lower NSCLC patients.

Abstract 6117: Characterizing cancer patterns in Okinawan vs. mainland Japanese Americans: The Multiethnic Cohort

Abstract Differences in chronic disease rates have been documented in Japan between Okinawa and mainland Japan. Limited data exist on whether these differences are also present in Okinawans and mainland Japanese who have migrated to the US. We used genotyped genome-wide association study data from the Multiethnic Cohort Study (MEC) to identify Japanese Americans of Okinawan or mainland ancestral similarity, and to investigate these two groups for differences in baseline chronic disease risk factors and for incidence of the four most common cancers during follow-up after blood draw. Cancer cases were identified via linkage to state cancer registries. Principal component analysis followed by uniform manifold approximation and projection (UMAP) was run using 15,678 single nucleotide polymorphisms among the 24,484 MEC Japanese Americans with blood samples. The Okinawan cluster was confirmed by labeling male MEC participants with Okinawan surnames on UMAP plots. Hazard ratios (HR), 95% confidence intervals (CI), and two-sided p-values were reported for Cox proportional hazards models, comparing cancer incidence between Okinawan and mainland Japanese individuals. The Okinawan cluster included 3,649 individuals (15% of the MEC Japanese Americans) and the mainland Japanese cluster included 19,611 individuals (80% of the MEC Japanese Americans). Small clusters of part-Okinawan and/or part-mainland Japanese (5% of the MEC Japanese Americans) were not included in the analysis. Ninety-six percent of Okinawan Americans and 94% of mainland Japanese Americans in MEC were born in the US. Okinawans were more likely to have a higher body mass index and daily alcohol intake, and less likely to be a current or former smoker, compared to mainland Japanese (all p-values&amp;lt;0.05). Post-menopausal Okinawan women were significantly more likely to be diagnosed with breast cancer (age-adjusted HR=1.39, 95% CI=1.10-1.75) compared to post-menopausal mainland Japanese women. This association was not modified by adjusting for additional known breast cancer risk factors (HR=1.36, 95% CI=1.07-1.73). Okinawans were also less likely to be diagnosed with lung cancer (HR=0.75, 95% CI=0.58-0.98); however, this association was no longer significant when adjusting for known risk factors, including smoking history (HR=0.82, 95% CI=0.62-1.07). There were no significant differences in risk of colorectal or prostate cancer between Okinawan and mainland Japanese individuals. Our results in this US-based sample are consistent with recent trends of higher breast cancer and lower lung cancer age-adjusted incidence rates reported from Japan for the Okinawan prefecture compared to mainland prefectures. Investigating reasons for the observed breast cancer risk difference may identify new risk factors for this disease in the Okinawan and other populations. Citation Format: Samantha A. Streicher, Song-Yi Park, Charleston W. Chiang, Xin Sheng, David Bogumil, David V. Conti, Christopher A. Haiman, Lynne R. Wilkens, Loic Le Marchand. Characterizing cancer patterns in Okinawan vs. mainland Japanese Americans: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6117.

Metastatic pathways to the lower zone by segment in patients with clinical T1 lower lobe non-small cell lung cancer.

Segmentectomy and mediastinal lymph node dissection (LND) may increasingly be used for non-small cell lung cancer (NSCLC). Lymph node metastasis (LNM) distribution varies by lower lobe segments; however, its segment-specific spread to the lower zone (#8, 9) (LZ) in lower lobe NSCLC is seldom reported. In total, 352 patients with clinical T1 lower lobe NSCLC who underwent lobectomy with systematic or lobe-specific LND were included for analysis between January 2006 and December 2018. Fifty-eight (16.2%) patients had LNM (pN1: 24, pN2: 34), and nine (2.6%) had LZ metastasis. LZ metastasis was significantly more frequent in tumors with diameter > 2cm, tumors without ground-glass opacity on radiological findings, left lung cancer, and basal segment lung cancer (respectively, p = 0.039, 0.006, 0.0177, 0.0024). None of the S6 NSCLC patients had LZ metastasis. Two patients with right basal segment NSCLC had LZ metastases (tumor on S10) as well as N1 lymph node and subcarinal zone metastasis. Seven (8.4%) patients with left basal segment NSCLC had LZ metastasis (tumor on S8: 3, tumor on S10: 4). Of them, three patients with left basal NSCLC had isolated LZ metastasis. The LND of the LZ can be omitted for clinical T1 patients with S6 NSCLC. In addition, the LND of the LZ may be omitted in right basal NSCLC if intraoperative confirmation of negative N1 and subcarinal zone lymph nodes is obtained; however, it is necessary for left basal segment NSCLC.

The interaction effects of zinc and polygenic risk score with benzo[a]pyrene exposure on lung cancer risk: A prospective case-cohort study among Chinese populations

The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.

Lower respiratory tract microbiome and lung cancer risk prediction in patients with diffuse lung parenchymal lesions.

In clinical practice, imaging manifestations of diffuse lung parenchymal lesions are common and indicative of various diseases, making differential diagnosis difficult. Some of these lesions are eventually diagnosed as lung cancer. Because respiratory microorganisms play an important role in lung cancer development, we searched for microbial markers that could predict the risk of lung cancer by retrospectively analyzing the lower respiratory tract (LRT) microbiome of 158 patients who were hospitalized in the First Affiliated Hospital of Guangzhou Medical University (March 2021-March 2023) with diffuse lung parenchymal lesions. The final diagnosis was lung cancer in 21 cases, lung infection in 93 cases, and other conditions (other than malignancy and infections) in 44 cases. The patient's clinical characteristics and the results of metagenomic next-generation sequencing of bronchoalveolar lavage fluid (BALF) were analyzed. Body mass index (BMI) and LRT microbial diversity (Shannon, Simpson, species richness, and Choa1 index) were significantly lower (P< 0.001, respectively) and Lactobacillus acidophilus relative abundance in the LRT was significantly higher (P< 0.001) in patients with lung cancer. The relative abundance of L. acidophilus in BALF combined with BMI was a good predictor of lung cancer risk (area under the curve = 0.985, accuracy = 98.46%, sensitivity = 95.24%, and specificity = 100.00%; P< 0.001). Our study showed that an imbalance in the component ratio of the microbial community, diminished microbial diversity, and the presence of specific microbial markers in the LRT predicted lung cancer risk in patients with imaging manifestations of diffuse lung parenchymal lesions.

A Statistical Testing Strategy Accounting for Random and Nonrandom (Skewed) X-Chromosome Inactivation Identifies Lung Cancer Susceptibility Loci among Smokers.

Lung cancer is the most common cancer worldwide in mortality and the second in incidence. Epidemiological studies found a higher lung cancer risk for smoking women in comparison to men, but these sex differences, irrespective of smoking habits, remain controversial. One of the hypotheses concerns the genetic contribution of the sex chromosomes. However, while genome-wide association studies identified many lung cancer susceptibility loci, these analyses have excluded X-linked loci. To account for nongenetic factors, we first presented an association test based on an additive-multiplicative hazard model accounting for random/nonrandom X-inactivation process. A simulation study was performed to investigate the properties of the proposed test as compared with the Wald test from a Cox model with random X-inactivation process and the partial likelihood ratio test proposed by Xu et al. accounting for nonrandom X-inactivation process. Then, we performed an X chromosome-wide association study on 9,261 individuals from the population-based cohort CARTaGENE to identify susceptibility loci for lung cancer among current and past smokers. We adjusted for the PLCOm2012 lung cancer risk score used in screening programs. Simulation results show the good behavior of the proposed test in terms of power and type I error probability as compared to the Xu et al. and the Wald test. Using the proposed test statistic and adjusting for the PLCOm2012 score, the X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 (p = 2.75×10-9) and rs12835699 (p = 1.26×10-6). For both SNPs, the minor allele was associated with lower lung cancer risk. Adjusting for multiple testing, no signal was detected using the Wald or the Xu et al. likelihood ratio tests. By taking into account smoking behavior and the X-inactivation process, the investigation of the X chromosome has shed a new light on the association between X-linked loci and lung cancer. We identified two loci associated with lung cancer located in the IL1RAPL1 gene. This finding would have been overlooked by examining only results from other test statistics.

Sex differences in chronic obstructive pulmonary disease characteristics: the Korea National Health and Nutrition Examination Survey 2007-2018.

Chronic obstructive pulmonary disease (COPD) is less prevalent in females than males, but it affects mortality in females. There may be sex differences in the clinical characteristics of COPD. We analyzed the Korea National Health and Nutrition Examination Survey dataset from 2007 to 2018. We compared the clinical characteristics and comorbidities in subjects with COPD according to sex. We adjusted the multivariate logistic regression of lung cancer prevalence according to COPD and sex by age and smoking amount. Females with COPD tended to be older than males with COPD (64.1 ± 0.4 yr vs. 62.3 ± 0.2 yr, respectively, p < 0.001). Approximately 89% of males with COPD had a smoking history, while 86% of females with COPD were non-smokers (p < 0.001). Household income was lower (p < 0.001) and asthma and overall malignancy were more prevalent in females with COPD than males with COPD (25.5 vs. 11.6%, respectively, p < 0.001; (6.3 vs. 5.4%, respectively, p < 0.001). However, lung cancer was more common in males with COPD than females with COPD (0.9 vs. 0.1%, respectively, p < 0.001). Lung cancer prevalence increased in males with moderate COPD compared to subjects without COPD (OR, 4.409; 95% CI, 1.741-9.419). Females with COPD had a lower smoking rate, household income, and lung cancer prevalence than males with COPD. More active COPD screening is needed for women of low socioeconomic status, even if they do not smoke.

Opportunistic Screening With Low-Dose Computed Tomography and Lung Cancer Mortality in China

Despite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality. To evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China. This cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023. Data collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening. Follow-up outcome indicators included lung cancer-specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis. A total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64). In this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.

Risk factors for early-onset lung cancer in Korea: analysis of a nationally representative population-based cohort.

We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. The study included 6,794,287 individuals aged 20-39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (<10 pack-years: mHR, 1.12; 95% CI, 1.01 to 1.24; ≥10 pack-years: mHR, 1.30; 95% CI, 1.18 to 1.45), but past smoking was not. Although mild alcohol consumption (<10 g/day) was associated with lower lung cancer risk (mHR, 0.92; 95% CI, 0.86 to 0.99), heavier alcohol consumption (≥10 g/day) was not. Higher income (highest vs. lowest quartile: mHR, 0.86; 95% CI, 0.78 to 0.94), physical activity for at least 1,500 metabolic equivalent of task-min/wk (vs. non-exercisers: mHR, 0.83; 95% CI, 0.69 to 0.99) and obesity (vs. normal weight: mHR, 0.89; 95% CI, 0.83 to 0.96) were associated with lower lung cancer risk, whereas metabolic syndrome was associated with increased risk (mHR, 1.13; 95% CI, 1.03 to 1.24). In young adults, age, female sex, smoking, and metabolic syndrome were risk factors for early-onset lung cancer, while high income, physical activity, and obesity displayed protective effects.

Increasing Lung Cancer Screening for High-Risk Smokers in a Frontier Population.

Northern Plains American Indians (AIs) have some of the highest smoking and lung cancer mortality rates in the USA. They are a high-risk population in which many are eligible for low-dose computed tomography (LDCT) screening, but such screening is rarely used. This study investigated methods to increase LDCT utilization through both a provider and community intervention to lower lung cancer mortality rates. This study used the Precaution Adoption Model for provider and community interventions implemented in four study regions in western South Dakota. The goal was to increase LDCT screening for eligible participants. Intake surveys and LDCT screenings were compared at baseline and 6months following the education programs for both interventions. A total of 131 providers participated in the provider intervention. At the 6-month follow-up survey, 31 (63%) referred at least one patient for LDCT (p < 0.05). Forty (32.3%) community participants reported their provider recommended an LDCT and of those, 30(75%) reported getting an LDCT (p < 0.05). A total of 2829 patient surveys were completed at the imaging sites and most (88%, n = 962) cited provider recommendation as their reason for obtaining an LDCT. Almost half (46%; n = 131) of the referring providers attended a provider education workshop, and 73% of the providers worked at a clinic that hosted at least one community education session. Over the study period, LDCT utilization increased from 640 to 1706, a 90.9% increase. The provider intervention had the strongest impact on LDCT utilization. This study demonstrated increased LDCT utilization through the provider intervention but increases also were documented for the other intervention combinations. The community-based education program increased both community and provider awareness on the value of LDCTs to lower lung cancer mortality rates.

Racial, ethnic and gender trends in lung cancer mortality rates in the United States-Mexico border and non-border areas

BackgroundGeographic patterns of lung cancer mortality rate differ in the region bordering Mexico in contrast to the US. This study compares lung cancer mortality between border and non-border counties by race/ethnicity and gender. MethodsThis study utilized population-level death certificate data from US Centers for Disease Control and Prevention Public Internet Wide-Ranging Online Data for Epidemiologic Research dataset between 1999 and 2020. Established algorithms were implemented to examine lung cancer deaths among US residents. We analyzed the age-adjusted data by year, race/ethnicity, gender, and geographic region. Joinpoint regression was used to determine mortality trends across time. ResultsLung cancer mortality rates were lower in border counties compared to non-border counties across time (p < 0.05). Hispanic lung cancer mortality rates were not different in border counties compared to non-border counties during the same period (p > 0.05). Lung cancer mortality among non-Hispanic White living in border counties was lower than non-Hispanic White residing in non-border counties (p < 0.01), and non-Hispanic Black living in border counties had lower lung cancer mortality than non-Hispanic Black in non-border counties in all but three years (p < 0.05). Both female and male mortality rates were lower in border counties compared to non-border counties (p < 0.05). ConclusionDifferences in lung cancer mortality between border counties and non-border counties reflect lower mortality in Hispanics overall and a decline for non-Hispanic White and non-Hispanic Black living in border counties experiencing lower lung cancer mortality rates than non-border counties. Further studies are needed to identify specific causes for lower mortality rates in border counties.