Additional impact of genetic ancestry over race/ethnicity to prevalence of KRAS mutations and allele-specific subtypes in non-small cell lung cancer.

The KRAS mutation is the most common oncogenic driver in patients with non-small cell lung cancer (NSCLC). However, a detailed understanding of how self-reported race and/or ethnicity (SIRE), genetically inferred ancestry (GIA), and their interaction affect KRAS mutation is largely unknown. Here, we investigated the associations between SIRE, quantitative GIA, and KRAS mutation and its allele-specific subtypes in a multi-ethnic cohort of 3,918 patients from the Boston Lung Cancer Survival cohort and the Chinese OrigiMed cohort with an independent validation cohort of 1,450 patients with NSCLC. This comprehensive analysis included detailed covariates such as age at diagnosis, sex, clinical stage, cancer histology, and smoking status. We report that SIRE is significantly associated with KRAS mutations, modified by sex, with SIRE-Asian patients showing lower rates of KRAS mutation, transversion substitution, and the allele-specific subtype KRASG12C compared to SIRE-White patients after adjusting for potential confounders. Moreover, GIA was found to correlate with KRAS mutations, where patients with a higher proportion of European ancestry had an increased risk of KRAS mutations, especially more transition substitutions and KRASG12D. Notably, among SIRE-White patients, an increase in European ancestry was linked to a higher likelihood of KRAS mutations, whereas an increase in admixed American ancestry was associated with a reduced likelihood, suggesting that quantitative GIA offers additional information beyond SIRE. The association of SIRE, GIA, and their interplay with KRAS driver mutations in NSCLC highlights the importance of incorporating both into population-based cancer research, aiming to refine clinical decision-making processes and mitigate health disparities.

Racial Disparities in Early-Stage NSCLC Treatment: A Call for Action.

Non-small cell lung cancer (NSCLC) is associated with a 5-year survival rate of only 28%; however, when caught at an early stage, it can be cured with surgery or stereotactic body radiotherapy (SBRT). Unfortunately, racial disparities may result in limited access to care for some patients. Liu and colleagues analyzed 64,999 cases of early-stage NSCLC treated between 2005 and 2017 from the Florida Cancer Registry and showed that Black patients had 36% lower odds of receiving curative-intent surgery compared with their White counterparts. This study highlights significant racial disparities in treatment patterns that must be addressed urgently. See related article by Liu and colleagues, Cancer Epidemiol Biomarkers Prev 2024;33:489-99.

Racial and ethnic disparities in genomic testing among lung cancer patients: a systematic review.

BACKGROUND: Racial and ethnic disparities in genomic testing could exacerbate disparities in access to precision cancer therapies and survival-particularly in the context of lung cancer where genomic testing has been recommended for the past decade. However, prior studies assessing disparities in genomic testing have yielded mixed results. METHODS: We conducted a systemic review to examine racial and ethnic disparities in the use of genomic testing among lung cancer patients in the United States. Two comprehensive searches in PubMed, Embase, and Scopus were conducted (September 2022, May 2023). Original studies that assessed rates of genomic testing by race or ethnicity were included. Findings were narratively synthesized by outcome. RESULTS: The search yielded 2739 unique records, resulting in 18 included studies. All but 1 study were limited to patients diagnosed with non-small cell lung cancer. Diagnosis years ranged from 2007 to 2022. Of the 18 studies, 11 found statistically significant differences in the likelihood of genomic testing by race or ethnicity; in 7 of these studies, testing was lower among Black patients compared with White or Asian patients. However, many studies lacked adjustment for key covariates and included patients with unclear eligibility for testing. CONCLUSIONS: A majority of studies, though not all, observed racial and ethnic disparities in the use of genomic testing among patients with lung cancer. Heterogeneity of study results throughout a period of changing clinical guidelines suggests that minoritized populations-Black patients in particular-have faced additional barriers to genomic testing, even if not universally observed at all institutions.

Ethnicity-specific association between TERT rs2736100 (A > C) polymorphism and lung cancer risk: a comprehensive meta-analysis.

The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case-control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on 'TERT rs2736100 polymorphism and LC susceptibility' in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors.

Geographic Origin may Affect Outcomes for Hispanic Patients with Non-Small Cell Lung Cancer in the United States.

BACKGROUND: Social determinants of health thoroughly explored in the literature include insurance status, race, and ethnicity. There are over 50 million self-identifying Hispanics in the United States. This, however, represents a heterogeneous population. We used a national registry to investigate for significant differences in outcomes of Hispanic patients with non-small cell lung cancer (NSCLC) in the Unites states, by geographic region of origin. MATERIALS AND METHODS: We identified a cohort of Hispanic patients in the Unites states with NSCLC for which region of origin was documented within the 2004 to 2016 National Cancer Database (NCDB) registry. This included patients from Cuba, Puerto Rico, Mexico, South and Central America, and the Dominican Republic. We performed multivariate logistic regression modeling to determine whether origin was a significant predictor of cancer staging at diagnosis, adjusting for age, sex, histology, grade, insurance status, and facility type. Race was not included due to a nonsignificant association with stage at diagnosis at the bivariate level in this cohort. Subsequently, we used Kaplan-Meier modeling to identify whether overall survival (OS) of Hispanic patients differed by origin. RESULTS: A total of 12,557 Hispanic patients with NSCLC were included in this analysis. The breakdown by origin was as follows: n = 2071 (16.5%) Cuban, n = 2360 (18.8%) Puerto Rican, n = 4950 (39.4%) Mexican, n = 2329 (18.5%) from South or Central America, and n = 847 (6.7%) from the Dominican Republic. After controlling for age, sex, histology, grade, insurance status and treating facility type, we found that geographic origin was a significant predictor of advanced stage at diagnosis (P = .015). Compared to Cubans, patients of Puerto Rican origin were less likely to present with advanced disease (68.4% vs. 71.9%; OR: 0.82; 95%CI: 0.69-0.98; P = .026). We also identified a significant (log-rank P-value<.001) difference in OS by geographic origin, even at early-stages of diagnosis. Dominican patients with NSCLC exhibited the highest 5-year OS rate (63.3%), followed by patients from South/Central America (59.7%), Puerto Rico (52.3%), Mexico (45.9%), and Cuba (43.8%). CONCLUSION: This study showed that for Hispanic individuals living in the Unites states, region/country of origin is significantly associated with outcomes, even after accounting for other known determinants of health. We suggest that region of origin should be studied further as a potential determinant of outcomes in patients with cancer.

Disruptive and Truncating TP53 Mutations Are Associated with African-Ancestry and Worse Prognosis in Brazilian Patients with Lung Adenocarcinoma.

INTRODUCTION: TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil. METHODS: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive and as truncating/nontruncating. We also assessed genetic ancestry using 46 ancestry-informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. We further examined associations of TP53 mutations with patients' clinicopathological features. RESULTS: TP53 mutations were detected in 64.3% (n = 287/446) of NSCLC cases, with a prevalence of 60.4% (n = 221/366) in lung adenocarcinomas. TP53 mutations were associated with brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. Disruptive and truncating mutations were associated with a younger age at diagnosis. Additionally, cBioportal dataset revealed that TP53 mutations were associated with younger age and Black skin color. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/nontruncating and wild-type patients. CONCLUSION: TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival.

Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK-Inhibitor-Naive ALK+ Non-Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study.

BACKGROUND: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor with demonstrated efficacy in locally advanced and metastatic non-small cell lung cancer (NSCLC) in crizotinib-refractory and ALK inhibitor-naive settings. This analysis assessed brigatinib in Asian vs. non-Asian patients from the first-line ALTA-1L trial. PATIENTS AND METHODS: This was a subgroup analysis from the phase III ALTA-1L trial of brigatinib vs. crizotinib in ALK inhibitor-naive ALK+ NSCLC. The primary endpoint was progression-free survival (PFS) as assessed by blinded independent review committee (BIRC). Secondary endpoints included confirmed objective response rate (ORR) and overall survival (OS) in the overall population and BIRC-assessed intracranial ORR and PFS in patients with brain metastases. RESULTS: Of the 275 randomized patients, 108 were Asian. Brigatinib showed consistent superiority in BIRC-assessed PFS vs. crizotinib in Asian (hazard ratio [HR]: 0.35 [95% CI: 0.20-0.59]; log-rank P = .0001; median 24.0 vs. 11.1 months) and non-Asian (HR: 0.56 [95% CI: 0.38-0.84]; log-rank P = .0041; median 24.7 vs. 9.4 months) patients. Results were consistent with investigator-assessed PFS and BIRC-assessed intracranial PFS. Brigatinib was well tolerated. Toxicity profiles and dose modification rates were similar between Asian and non-Asian patients. CONCLUSION: Efficacy with brigatinib was consistently better than with crizotinib in Asian and non-Asian patients with locally advanced or metastatic ALK inhibitor-naive ALK-+ NSCLC. There were no clinically notable differences in overall safety in Asian vs. non-Asian patients.

Efficacy and safety of lorlatinib in Asian and non-Asian patients with ALK-positive advanced non-small cell lung cancer: Subgroup analysis of a global phase 2 trial.

OBJECTIVES: To analyze the efficacy and safety of lorlatinib in Asian and non-Asian patients with pretreated anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC) from a phase 1/2 study. MATERIALS AND METHODS: In this ongoing phase 2 part of the trial, patients with ALK- or ROS1-positive, advanced NSCLC enrolled into six expansion cohorts (EXP1-6), based on ALK and ROS1 status and previous therapy, and received lorlatinib 100 mg once daily. The primary endpoint was objective tumor response and intracranial response. Post hoc analyses of activity were conducted in Asian and non-Asian (based on race) ALK-positive patients who received either previous crizotinib with or without chemotherapy (EXP2-3A) or at least one second-generation ALK tyrosine kinase inhibitor with any number of chemotherapy regimens (EXP3B-5). Analysis of safety (adverse events [AEs]) was in the phase 1 and 2 study population who started lorlatinib 100 mg once daily. RESULTS: 17 Asian patients were enrolled in EXP2-3A and 53 in EXP3B-5; 33 non-Asian patients were enrolled in EXP2-3A and 73 in EXP3B-5. Objective response rates in the Asian and non-Asian subgroups were 82.4% (95% confidence interval [CI]: 56.6-96.2) and 63.6% (95% CI: 45.1-79.6) in EXP2-3A, and 47.2% (95% CI: 33.3-61.4) and 30.1% (95% CI: 19.9-42.0) in EXP3B-5, and median progression-free survival was 13.6 and 12.5 months (EXP2-3A) and 6.9 and 5.5 months (EXP3B-5). Lorlatinib exhibited antitumor activity across ALK resistance mutations, while no differences according to the EML4-ALK variant could be detected. The most common treatment-related AEs were hypercholesterolemia, hypertriglyceridemia, edema, and peripheral neuropathy in both Asian and non-Asian subgroups. CONCLUSION: Lorlatinib showed substantial overall and intracranial activity in pretreated patients with ALK-positive NSCLC in both Asian and non-Asian patients. AE profiles were similar between Asian and non-Asian patients. CLINICALTRIALS: gov NCT01970865.

The association of TAP polymorphisms with non-small-cell lung cancer in the Han Chinese population.

The host immune system plays a crucial role in multiple types of cancer, including non-small-cell lung cancer (NSCLC). Transporter associated with antigen processing (TAP) protein heterodimer complexes might promote intracellular antigen peptide binding with class I major histocompatibility complex (MHC-I) molecules, and in recent years, TAP1 and TAP2 have been reported to be associated with multiple cancer risks. In the current study, we investigated the association of single-nucleotide polymorphisms (SNPs) in TAP1 and TAP2 with NSCLC in a Han Chinese population. Six and seven TAP1 and TAP2 SNPs, respectively, were genotyped and analysed in healthy controls and NSCLC patients. Based on our data, none of the six SNPs in TAP1 is associated with NSCLC risk (P > 0.0038). However, rs2228396 alleles in TAP2 were significantly different between NSCLC patients and healthy controls, and the A allele might be associated with an increased risk of this cancer (P = 0.001, OR = 1.65, 95%CI: 1.23 ∼ 2.21). Moreover, the genotype frequencies of rs2228396 were significantly different between patients and healthy controls (P = 7 × 10-4). Additionally, TAP2 rs241441 alleles exhibited a trend of difference between NSCLC patients and healthy controls, with the C allele possibly being associated with increased risk of NSCLC (P = 0.013; OR = 1.30, 95%CI: 1.06 ∼ 1.60). Moreover, the genotypes of rs241441 in TAP2 showed a significant difference between NSCLC patients and healthy controls (P = 1 × 10-4). In haplotype analysis, the TAP2 SNP haplotype (CAC, TAP2*0102) was significantly associated with increased NSCLC risk in the Han Chinese population (P = 0.003; OR = 1.57, 95%CI: 1.17 ∼ 2.10). Our results indicate that TAP2 SNPs (rs2228396 and rs241441) have a potential role in NSCLC pathogenesis.

Genome-wide gene-smoking interaction study identified novel susceptibility loci for non-small cell lung cancer in Chinese populations.

Gene-smoking interactions play important roles in the development of non-small cell lung cancer (NSCLC). To identify single-nucleotide polymorphisms (SNPs) that modify the association of smoking behavior with NSCLC risk, we conducted a genome-wide gene-smoking interaction study in Chinese populations. The genome-wide interaction analysis between SNPs and smoking status (ever- versus never-smokers) was carried out using genome-wide association studies of NSCLC, which included 13 327 cases and 13 328 controls. Stratified analysis by histological subtypes was also conducted. We used a genome-wide significance threshold of 5 × 10-8 for identifying significant gene-smoking interactions and 1 × 10-6 for identifying suggestive results. Functional annotation was performed to identify potential functional SNPs and target genes. We identified three novel loci with significant or suggestive gene-smoking interaction. For NSCLC, the interaction between rs2746087 (20q11.23) and smoking status reached genome-wide significance threshold [odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.54-0.74, P = 3.31 × 10-8], and the interaction between rs11912498 (22q12.1) and smoking status reached suggestive significance threshold (OR = 0.72, 95% CI: 0.63-0.82, P = 8.10 × 10-7). Stratified analysis by histological subtypes identified suggestive interactions between rs459724 (5q11.2) and smoking status (OR = 0.61, 95% CI: 0.51-0.73, P = 7.55 × 10-8) in the risk of lung squamous cell carcinoma. Functional annotation indicated that both classic and novel biological processes, including nicotine addiction and airway clearance, may modulate the susceptibility to NSCLC. These novel loci provide new insights into the biological mechanisms underlying NSCLC risk. Independent replication in large-scale studies is needed and experimental studies are warranted to functionally validate these associations.

Association of ERBB4 genetic polymorphism with the risk and prognosis of non-small cell lung cancer in Chinese Han population: A population-based case-control study.

ABSTRACT: The aim of this study was to explore the association of rs1836724 single-nucleotide polymorphism (SNP) of ERBB4 with risk and prognosis of non-small cell lung cancer (NSCLC) in the Chinese Han population.The genotype of rs1836724 SNP of ERBB4 from 258 patients with NSCLC and 200 noncancer controls were detected the TaqMan-MGB probes real-time fluorescence polymerase chain reaction. The distribution of genotype and alleles between the 2 groups was compared, and the association between clinicopathological characteristic and rs1836724 SNP was analyzed. Prognosis and influencing factors were analyzed by Kaplan-Meier and Cox regression analysis.There were significant differences in the genotype and allele distribution of ERBB4 rs1836724 between the NSCLC group and control group (P < .05). And CC genotype of rs1836724 was associated with increased risk of NSCLC in the Chinese Han population. Rs1836724 SNP was associated with TNM stage and lymph nodal metastasis (P = .001, P = .007). The median follow-up was 29 months, and the progression-free survival and overall survival of 258 NSCLC patients were 27.91% and 31.39%, respectively. Patients with GG genotype of rs1836724 had poor progression-free survival and overall survival. Rs1836724 SNP was an independent prognostic marker of NSCLC patients, CC genotype had a high risk of poor prognosis (odds ratio = 1.587, 95% confidence interval: 1.079-2.335, P = .019).In Chinese Han populations, rs1836724 SNP of ERBB4 may contribute toward the increased risk and poor prognosis of NSCLC.

Population-based incidence rates and increased risk of EGFR mutated non-small cell lung cancer in Maori and Pacifica in New Zealand.

BACKGROUND: Non-squamous non-small cell lung cancer (NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) mutation benefit from targeted treatments. Previous studies reported EGFR mutation-positive proportions among tested non-squamous NSCLC patients. However, incidence rates and population risk of EGFR mutation-positive and EGFR mutation-negative non-squamous NSCLC have not been assessed. This study therefore aimed to estimate the population-based incidence rates of EGFR mutation-positive and EGFR mutation-negative non-squamous NSCLC in different population groups defined by sex, ethnic group and smoking status. METHODS: This study included data from all non-squamous NSCLC patients diagnosed in northern New Zealand between 1/02/2010 and 31/07/2017 (N = 3815), obtained from a population-based cancer registry. Age-specific incidence rates, WHO age-standardised rates (ASRs) and rates adjusted for incomplete testing were calculated for EGFR mutation-positive and EGFR mutation-negative diseases for the study cohort as a whole and subgroups of patients. RESULTS: Among 3815 patients, 45% were tested for EGFR mutations; 22.5% of those tested were EGFR mutation-positive. The ASR of EGFR mutation-positive NSCLC was 5.05 (95%CI 4.71-5.39) per 100,000 person-years. ASRs for EGFR mutation-positive NSCLC were higher for females than males: standardised incidence ratio (SIR) 1.50 (1.31-1.73); higher for Pacifica, Asians and Maori compared with New Zealand Europeans: SIRs 3.47 (2.48-4.85), 3.35 (2.62-4.28), and 2.02 (1.43-2.87), respectively; and, only slightly increased in ever-smokers compared with never-smokers: SIR 1.25 (1.02-1.53). In contrast, the ASR of EGFR mutation-negative NSCLC was 17.39 (16.75-18.02) per 100,000 person-years, showing a strong association with smoking; was higher for men; highest for Maori, followed by Pacifica and then New Zealand Europeans, and lowest for Asians. When corrected for incomplete testing, SIRs by sex, ethnicity and smoking, for both diseases, remained similar to those based on tested patients. CONCLUSION: The population risk of EGFR mutation-positive NSCLC was significantly higher for Maori and Pacifica compared with New Zealand Europeans.

Disparate outcomes in nonsmall cell lung cancer by immigration status.

OBJECTIVE: The purpose of this study was to evaluate overall survival (OS) outcomes by race, stratified by country of origin in patients diagnosed with NSCLC in California. METHODS: We performed a retrospective analysis of nonsmall cell lung cancer (NSCLC) patients diagnosed between 2000 and 2012. Race/ethnicity was defined as White (W), Black (B), Hispanic (H), and Asian (A) and stratified by country of origin (US vs. non-US [NUS]) creating the following patient cohorts: W-US, W-NUS, B-US, B-NUS, H-US, H-NUS, A-US, and A-NUS. Three multivariate models were created: model 1 adjusted for age, gender, stage, year of diagnosis and histology; model 2 included model 1 plus treatment modalities; and model 3 included model 2 with the addition of socioeconomic status, marital status, and insurance. RESULTS: A total of 68,232 patients were included. Median OS from highest to lowest were: A-NUS (15 months), W-NUS (14 months), A-US (13 months), B-NUS (13 months), H-US (11 months), W-US (11 months), H-NUS (10 months), and B-US (10 months) (p < 0.001). In model 1, B-US had worse OS, whereas A-US, W-NUS, B-NUS, H-NUS, and A-NUS had better OS when compared to W-US. In model 2 after adjusting for receipt of treatment, there was no difference in OS for B-US when compared to W-US. After adjusting for all variables (model 3), all race/ethnicity profiles had better OS when compared to W-US; B-NUS patients had similar OS to W-US. CONCLUSION: Foreign-born patients with NSCLC have decreased risk of mortality when compared to native-born patients in California after accounting for treatments received and socioeconomic differences.

Mutation differences in circulating tumor DNAs from non-small cell lung cancer patients between Uygur and Han populations.

BACKGROUND: The incidence of non-small cell lung cancer (NSCLC) in Uygur population is gradually increasing recently. In view of the great diagnostic and prognostic values of cell-free DNAs (cfDNA) detection, this study focus on a liquid biopsy to explore the value of cfDNA mutation in healthy and NSCLC patients in 2 ethnicities. METHODS: The concentration and sequencing of cfDNA in NSCLC and healthy subjects was assessed with a standard information analysis procedure, including detection, annotation, and statistical analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to analyze the function of mutant genes and related pathways. Totally, 133 subjects, including 35 Uygur NSCLC patients, 10 Uygur healthy subjects, 63 cases of Han NSCLC patients and 25 Han health control, were admitted to the hospital. RESULTS: There were a lower proportion of adenocarcinoma and higher percentage of smoking rate for Uygur patients. For cfDNA level between NSCLC and healthy subjects, Han patients exhibited sharp increase while there was no statistical difference in Uygur population. In addition, the mutation frequency of cfDNA in Han patients (72.6%) was significantly higher than Uygur patients (45.7%). There were 5 gene mutations only found in Han patients and ABCC11 showed a higher mutation frequency in Uygur population as a common one. Finally, Go and Kyoto Encyclopedia of Genes and Genomes analysis showed apprent functional enrichments and pathway changes between 2 ethnicities. CONCLUSION: There existed distinct distributions of cancer subtypes, smoking proportion, cfDNA level, and mutation patterns between Han and Uygur patients. The results may be a useful tool in NSCLC patients' diagnosis as well as individualized therapy between ethnicities in future.

Next Generation Sequencing of Advanced Non-Small Cell Lung Cancer: Utilization Based on Race and Impact on Survival.

BACKGROUND: Next generation sequencing (NGS) of tumor of patients with advanced non-small cell lung cancer (NSCLC) is now a standard of care that informs the clinician on the best therapeutic approach for their patients. The purpose of our study was to investigate the overall impact of NGS testing on survival as well as potential racial differences in utilization, therapeutic decision, and genomic alterations. METHOD: Using a large institutional database, 928 patients with stage IV NSCLC were identified. NGS testing using Foundation One platform was used. Clinical and genomic characteristics were compared by race. We used a propensity-modeling technique to compare groups that were sequenced or not in terms of overall survival. Time to event data was analyzed using Kaplan-Meier method and Cox model. RESULTS: A total of 295 patients underwent NGS. Patients undergoing NGS testing had significantly longer survival of 25.3 months versus those who did not undergo sequencing with a median survival of 14.6 months (P = .002) irrespective if they received targeted therapy or not. There was no difference in terms of NGS utilization based on race (P = .32). African American individuals had significantly higher rates of ALK rearrangements and mutations in PBRM1, SETD2, TSC2, and FBXW7. CONCLUSION: Our study demonstrates that within a large single institution there is no racial difference in NGS utilization and that NGS testing directly impacts survival. We identify a number of differences in genomic findings between African American and white individuals.

External Validation of AJCC Eighth Edition of Non-small-cell Lung Cancer Staging Among African Americans.

INTRODUCTION: The American Joint Committee on Cancer (AJCC) eighth staging classification system for non-small-cell lung cancer was based on data from a multinational study consisting of 94,708 patients. African Americans were not included in this large database. MATERIALS AND METHODS: The authors aimed to compare the performance of the AJCC eighth staging system with that of the seventh in predicting overall survival among African Americans utilizing the National Cancer Database. Cases with T- and M- categories were classified into 2 groups based on the AJCC seventh and eighth edition staging systems. Kaplan-Meier curves for overall survival were then constructed for each subgroup. Concordance index was computed using Uno's methodology to assess the overall performance between the 2 staging systems in predicting the mortality. Time-dependent area under the curve was calculated at each follow-up event for the seventh and eighth edition clinical and pathologic staging using an inverse probability of censoring weighted methodology. A 2-sided P-value < .05 was considered to show statistical significance. RESULTS: The database identified a total of 70,606 African American patients in the study period of 2004 through 2014. Area under the curve values were consistently higher for the eighth edition scheme compared with the seventh edition (concordance 0.630 vs. 0.624, respectively; P < .0001 for clinical staging scheme and 0.596 vs. 0.591, respectively; P = .01 for pathologic staging scheme). CONCLUSION: The AJCC eighth edition staging system showed better prognostic value in predicting overall survival when compared with the AJCC seventh edition staging scheme among African American patients with non-small-cell lung cancer.

Diagnostic value of microRNA-25 in patients with non-small cell lung cancer in Chinese population: A systematic review and meta-analysis.

OBJECTIVE: Previous studies have shown that microRNA-25 (miR-25) plays a key role in the occurrence and development of non-small cell lung cancer (NSCLC). Many studies have shown that there is a significant increment of miR-25 in circulating blood of patients with NSCLC. The meta-analysis aims to explore diagnostic value of miR-25 in NSCLC in Chinese population. METHODS: PubMed, Web of science, Excerpta Medica Database, China national knowledge infrastructure and China Wanfang database were searched to collect studies upon correlation between miR-25 and diagnosis of the patients with NSCLC until April 2020. Combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristic curve were calculated by Stata 15.0 software. Literature assessment was conducted according to quality assessment of diagnostic accuracy studies, and documents with scores above or equal to 11 were included in this meta-analysis. RESULTS: Six studies were included, including 480 cases with NSCLC and 451 healthy controls. The combined sensitivity (0.75, 95% confidence interval [CI]: 0.69∼0.80), specificity (0.81, 95% CI: 0.76∼0.86), positive likelihood ratio (4.04, 95% CI: 3.14∼5.20), negative likelihood ratio (0.31, 95% CI: 0.25∼0.37), diagnostic odds ratio (13.09, 95% CI: 9.37∼18.29) and area under curve (0.85, 95% CI: 0.82∼0.88) indicated that miR-25 had desirable diagnostic accuracy for NSCLC. CONCLUSION: MiR-25 can be applied in diagnosis of NSCLC and has potential of becoming a biomarker for detection of patients with early NSCLC in Chinese population.

Pharmacogenetic Association between XRCC1 Polymorphisms and Response to Platinum-Based Chemotherapy in Asian Patients with NSCLC: A Meta-Analysis.

BACKGROUND: Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. METHODS: Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. RESULTS: Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln (OR = 1.71, 95% CI: 1.16-2.52, p = .007, I 2 = 56.8%) and GlnArg (OR = 1.23, 95% CI: 1.07-1.40, p = .003, I 2 = 29.0%) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS (HR = 0.60, 95% CI: 0.40-0.88) and PFS (HR = 0.64, 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73, 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28, 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. CONCLUSION: Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC.

Racial disparities in local therapy for early stage non-small-cell lung cancer.

OBJECTIVES: This study investigated disparities in the delivery of definitive therapy for early stage non-small-cell lung cancer (ESNSCLC) between Caucasian (CS) and African American (AA) populations. METHODS: The National Cancer Data Base was queried for AA and CS patients, diagnosed with c stage I Non small cell lung cancer between 2004 and 2015. Trends in surgery, stereotactic ablative radiotherapy (SABR), or external beam radiation therapy (EBRT) were compared. Kaplan-Meier and Cox hazards models were used to compare 5-year overall survival (5YOS). RESULTS: A total of 174,338 (90.6%) patients were CS and 18,077 (9.4%) patients were AA. AA patients were less likely to receive surgery (60.3% vs. 66.9%; p < .001) and more likely to receive EBRT (12.4% vs. 10.6%; p < .001); however, there was no significant difference in rates of SABR (8.8% vs. 9.2%; p = .066). From 2004 to 2015, the surgery rates increased for AA patients from 44.4% to 61.8% and for CS patients from 57.6% to 65.6%. AA patients had worse 5YOS on an unadjusted analysis (46.7% vs. 47.9%; p = .009). When adjusted for definitive treatment, AA patients had improved survival (hazard ratio = 0.97, 95% confidence interval = 0.94-0.99). CONCLUSION: Improvements in the delivery of surgery and equal utilization of definitive radiation therapy are at least partially responsible for closing the survival gap between AA and CS patients with ESNSCLC.

Ethnicity and insurance status predict metastatic disease presentation in prostate, breast, and non-small cell lung cancer.

BACKGROUND: Ethnicity and insurance status have been shown to impact odds of presenting with metastatic cancer, however, the interaction of these two predictors is not well understood. We evaluate the difference in odds of presenting with metastatic disease in minorities compared to white patients despite access to the same insurance across three common cancer types. METHODS: Using the National Cancer Database, a multilevel logistic regression model that estimated the odds of metastatic disease was fit, adjusting for covariates including year of diagnosis, ethnicity, insurance, income, and region. We included adults diagnosed with metastatic prostate, non-small cell lung cancer (NSCLC), and breast cancer from 2004 to 2015. RESULTS: The study cohort consisted of 1 191 241 prostate cancer (PCa), 1 310 986 breast cancer (BCa), and 1 183 029 NSCLC patients. Private insurance was the most protective factor against metastatic presentation. Odds of presenting with metastatic disease were 0.190 [95% CI, 0.182-0.198], 0.616 [95% CI, 0.602-0.630], and 0.270 [95% CI, 0.260-0.279] for PCa, NSCLC, and BCa compared to uninsured patients, respectively. Private insurance provided the most significant benefit to non-Hispanic White PCa patients with 81% reduction in odds of metastatic presentation and conferred the least benefit to African-American NSCLC patients at 30.4% reduction in odds of metastatic presentation. CONCLUSIONS: Insurance status provided the single most protective effect against metastatic presentation. This benefit varied for minorities despite similar insurance. Reducing metastatic disease presentation rates requires addressing social barriers to care independent of insurance.